Progesterone supplementation reverses 83% of transcript changes in the secretory endometrium induced by postovulatory mifepristone, potentially mitigating its antiprogestogenic effects. Mifepristone (RU486) antagonizes progesterone signaling in human endometrium interfering in the secretory phenotype after estradiol priming. The objective of the present study was to determine effect in the endometrial transcript profile of progesterone supplementation after the administration of 200 mg of the antiprogestin mifepristone 48 h after the LH peak (LH+2, LH+0 = LH peak). Endometrial samples were obtained on LH+7 after vaginal administration of micronized progesterone 200 mg/day for 3 days in nine women of proven fertility, each one contributing with one cycle treated with progesterone and another with a placebo. In addition, endometrial samples were obtained in LH+7 from a subgroup of four women with no administration of mifepristone, with each one contributing with one cycle treated with vaginal progesterone supplementation or placebo as a reference. RNA-seq was used to identify transcripts significantly regulated under the administration of progesterone vs placebo with or without postovulatory mifepristone. We observed that 713 transcripts changed significantly in the endometrium under mifepristone after progesterone supplementation in group A. Of these, progesterone reversed approximately 83% of the transcripts affected by mifepristone in the secretory endometrium. Bioinformatic analyses revealed that these transcripts were enriched in genes associated with mitochondrial function, particularly oxidative phosphorylation. In addition, NR2C2 and DLX1 were identified as potential transcription factors that may mediate the effects of progesterone in the endometrium. We conclude that progesterone supplementation after postovulatory mifepristone administration can reverse the antiprogestogenic effects for most of the affected endometrial transcripts.
Del Río JP et al., 2024·Front Psychol·
Open Access
Hormones produced by the hypothalamic-pituitary-adrenal-gonadal (HPAG) axis are crucial for modulating central nervous system (CNS) function and development throughout a person's life. Disruptions in HPAG function can impact psychological development, particularly during adolescence-a period marked by psychological growth and the maturation of the HPAG axis. An early indicator of HPAG alterations is ovulatory dysfunction (OD), a common condition among adolescents. This study explored the associations between neuroactive hormones and personal growth in adolescents with OD. Female participants aged 12-25 years with OD were recruited, and assessments were conducted to profile their basic hormonal levels and various dimensions of individual development, including self-concept clarity, sense of coherence, self-esteem, perfectionism, self-control, and mood states. Adolescents with OD (n = 117) had lower self-concept clarity and self-esteem compared to reference data. A significant portion of the sample displayed elevated levels of tension (71.25%), confusion (62.5%), fatigue (58.22%), and depression (52.6%). Self-esteem scores were negatively correlated with DHEAS (r = -0.224; p = 0.026) and glucose (r = -0.249; p = 0.010). Higher levels of free testosterone were associated with increased depression scores (coef = 0.2398; p = 0.002), whereas higher estradiol levels were linked to lower aggressiveness scores (coef = -0.0648; p = 0.001). These findings indicate that hormonal imbalances in adolescents with OD could affect personal growth. Further research is needed to establish causal relationships between the variables considered.
Vigil P et al., 2022·Front Endocrinol (Lausanne)·
Open Access
Obesity in women of reproductive age has a number of adverse metabolic effects, including Type II Diabetes (T2D), dyslipidemia, and cardiovascular disease. It is associated with increased menstrual irregularity, ovulatory dysfunction, development of insulin resistance and infertility. In women, estradiol is not only critical for reproductive function, but they also control food intake and energy expenditure. Food intake is known to change during the menstrual cycle in humans. This change in food intake is largely mediated by estradiol, which acts directly upon anorexigenic and orexigenic neurons, largely in the hypothalamus. Estradiol also acts indirectly with peripheral mediators such as glucagon like peptide-1 (GLP-1). Like estradiol, GLP-1 acts on receptors at the hypothalamus. This review describes the physiological and pathophysiological mechanisms governing the actions of estradiol during the menstrual cycle on food intake and energy expenditure and how estradiol acts with other weight-controlling molecules such as GLP-1. GLP-1 analogs have proven to be effective both to manage obesity and T2D in women. This review also highlights the relationship between steroid hormones and women's mental health. It explains how a decline or imbalance in estradiol levels affects insulin sensitivity in the brain. This can cause cerebral insulin resistance, which contributes to the development of conditions such as Parkinson's or Alzheimer's disease. The proper use of both estradiol and GLP-1 analogs can help to manage obesity and preserve an optimal mental health in women by reducing the mechanisms that trigger neurodegenerative disorders.
Duane M et al., 2022·Front Med (Lausanne)·
Open Access
Fertility awareness-based methods (FABMs) educate about reproductive health and enable tracking and interpretation of physical signs, such as cervical fluid secretions and basal body temperature, which reflect the hormonal changes women experience on a cyclical basis during the years of ovarian activity. Some methods measure relevant hormone levels directly. Most FABMs allow women to identify ovulation and track this "vital sign" of the menstrual or female reproductive cycle, through daily observations recorded on cycle charts (paper or electronic). Physicians can use the information from FABM charts to guide the diagnosis and management of medical conditions and to support or restore healthy function of the reproductive and endocrine systems, using a restorative reproductive medical (RRM) approach. FABMs can also be used by couples to achieve or avoid pregnancy and may be most effective when taught by a trained instructor. Information about individual FABMs is rarely provided in medical education. Outdated information is widespread both in training programs and in the public sphere. Obtaining accurate information about FABMs is further complicated by the numerous period tracking or fertility apps available, because very few of these apps have evidence to support their effectiveness for identifying the fertile window, for achieving or preventing pregnancy. This article provides an overview of different types of FABMs with a published evidence base, apps and resources for learning and using FABMs, the role FABMs can play in medical evaluation and management, and the effectiveness of FABMs for family planning, both to achieve or to avoid pregnancy.
Vigil P et al., 2022·Front Glob Womens Health·
Open Access
Stress is known to be associated with adverse health outcomes. The COVID-19 pandemic and its associated lockdowns are examples of chronic stressors. Lockdown measures inadvertently caused significant psychological distress and became a powerful source of anxiety/stress, sleep disturbances, nutritional changes and weight gain. Stress is known to impact women's health specifically, through hypothalamic-pituitary-gonadal (HPG) axis dysfunction and resultant ovulatory dysfunction. Such dysfunction may manifest in menstrual irregularities and/or infertility due to hypothalamic hypogonadism. Here, we review the key physiological mediators of stress and associated ovulatory dysfunction. The kisspeptinergic system is comprised of sets of neurons located in the hypothalamus, the rostral periventricular region of the third ventricle (RP3V) and the arcuate nucleus (ARC). This system links nutrition, reproductive signals and stress. It plays a key role in the function of the HPG axis. During chronic stress, the kisspeptinergic system affects the HPG axis, GnRH pulsatility, and, therefore, ovulation. Leptin, insulin and corticotrophin-releasing hormone (CRH) are thought to be additional key modulators in the behavioral responses to chronic stress and may contribute to stress-related ovulatory dysfunction. This mini-review also summarizes and appraises the available evidence on the negative impact of chronic stress as a result of the COVID-19 pandemic lockdowns. It proposes physiological mechanisms to explain the observed effects on women's reproductive health and well-being. The review suggests areas for future research.
Nutrition and Metabolic Health · Blood Sugar and Insulin
Olivera-Nappa Á et al., 2022·Front Nutr·
Open Access
A growing body of evidence indicates that dietary polyphenols could be used as an early intervention to treat glucose-insulin (G-I) dysregulation. However, studies report heterogeneous information, and the targets of the intervention remain largely elusive. In this work, we provide a general methodology to quantify the effects of any given polyphenol-rich food or formulae over glycemic regulation in a patient-wise manner using an Oral Glucose Tolerance Test (OGTT). We use a mathematical model to represent individual OGTT curves as the coordinated action of subsystems, each one described by a parameter with physiological interpretation. Using the parameter values calculated for a cohort of 1198 individuals, we propose a statistical model to calculate the risk of dysglycemia and the coordination among subsystems for each subject, thus providing a continuous and individual health assessment. This method allows identifying individuals at high risk of dysglycemia-which would have been missed with traditional binary diagnostic methods-enabling early nutritional intervention with a polyphenol-supplemented diet where it is most effective and desirable. Besides, the proposed methodology assesses the effectiveness of interventions over time when applied to the OGTT curves of a treated individual. We illustrate the use of this method in a case study to assess the dose-dependent effects of Delphinol® on reducing dysglycemia risk and improving the coordination between subsystems. Finally, this strategy enables, on the one hand, the use of low-cost, non-invasive methods in population-scale nutritional studies. On the other hand, it will help practitioners assess the effectiveness of an intervention based on individual vulnerabilities and adapt the treatment to manage dysglycemia and avoid its progression into disease.
Measurement and Statistics · Instrument Development and Validation
Contreras PH et al., 2019·J Endocr Soc·
Open Access
To evaluate the diagnostic performance of several biochemical predictors of insulin resistance (IR).
A total of 90 nondiabetic subjects were tested with both the pancreatic suppression test (PST) and the oral glucose tolerance test (OGTT). Of them, 53 were non-insulin-resistant (NIR) subjects and the remaining 37 were insulin resistant subjects. All glucose and insulin values from the OGTT were positively correlated with the steady-state plasma glucose (SSPG) value of the PST. Among the OGTT values, basal insulin (I0) displayed a stronger correlation with SSPG (r = 0.604). Receiver operating characteristic analysis of the OGTT data demonstrated that I0 exhibited the highest area under the receiver operating characteristic curve (AUROC), compared with the rest of the OGTT data. However, the reduced sensitivity of this predictor precluded its clinical use.We then tested six potential predictors of IR derived from the OGTT values. Of them, the I0*G60 had a correlation coefficient of 0.697 with the SSPG and an AUROC of 0.867, surpassing the respective values of the traditional biochemical predictors of IR. Its cutoff predicting IR was >1110 mg/dL*μΙU/mL (>428 nM*pM), its sensitivity was 0.865, and its global accuracy was 0.822. We then selected the six best biochemical predictors of IR according to their posttest probability ratio. The order was as follows: I0*G60, ISI composite, AUC-Gl*In/', quantitative insulin sensitivity check index, homeostatic model assessment 1 (HOMA1), and HOMA2. We conclude that the I0*G60 is a promising, inexpensive, and easily calculable predictor of IR that outperforms the predictive power of the traditional predictors of IR, including the insulin sensitivity index composite.
Contreras PH et al., 2018·Front Med (Lausanne)·
Open Access
A cohort of 141 males (18-80 yo, 42.9 ± 12.9) strongly suspected of being Insulin Resistant (IR) was prospectively studied by determining their insulin sensitivity (Pancreatic Suppression Test, PST) and testicular function (total testosterone and SHBG). The subjects were labeled as IR when the Steady State Plasma Glucose (SSPG) was ≥150 mg/dL and Non-Insulin Resistant (NIR) when SSPG was <150 mg/dl; similarly, the subjects were labeled as Hypogonadal (HYPOG) when total testosterone was ≤3.0 ng/mL and Eugonadal (EUG) when total testosterone was >3.0 ng/mL. Two out of three subjects turned out to be IR, while around one in four subjects were HYPOG. Contingency analysis indicated a significant interdependence between insulin resistance and hypogonadism (chi-square was 4.69, p = 0.0303). Age (>43 yo) predicted hypogonadism (AUROC 0.606, p = 0.0308). Twice as many HYPOG subjects were IR as compared with EUG subjects. Also, HYPOG subjects exhibited higher SSPG values as compared with EUG subjects. Statistically, neither Weight nor BMI predicted hypogonadism, while Waist Circumference (>110 cm) was only a mediocre predictor (AUROC 0.640, p = 0.009). SSPG (>224 mg/dL) on the other hand, was the best predictor of hypogonadism (AUROC 0.709, p = 0.002), outperforming Waist Circumference (half of the subjects with an SSPG >224 mg/dL were HYPOG). Age did not predict insulin resistance, while Weight (>99 kg), BMI (>29), and especially, Waist Circumference (>99 cm, AUROC 0.812, p < 0.0001) were all predictors of insulin resistance. Almost 90% of the subjects with a waist circumference >99 cm was IR. As a logical consequence of the selection criteria (various clues suggesting insulin resistance), most subjects with normal weight in this cohort were IR (53.3%) while 20% were HYPOG. On the other hand, 13.6% of the obese subjects were NIR, and 2 out of 3 of them were both NIR and EUG. In conclusion, Waist Circumference predicted both insulin resistance (>99 cm) and hypogonadism (>110 cm), suggesting that the first hit of abdominal obesity is insulin resistance and the second hit is male hypogonadism. Normal weight did not protect from IR, while a relevant proportion of obese subjects were NIR (with 2/3 being also EUG).
Del Río JP et al., 2018·Front Public Health·
Open Access
Sex hormones significantly impact women's lives. Throughout the different stages of life, from menarche to menopause and all stages in between, women experience dramatic fluctuations in the levels of progesterone and estradiol, among other hormones. These fluctuations affect the body as a whole, including the central nervous system (CNS). In the CNS, sex hormones act via steroid receptors. They also have an effect on different neurotransmitters such as GABA, serotonin, dopamine, and glutamate. Additionally, studies show that sex hormones and their metabolites influence brain areas that regulate mood, behavior, and cognitive abilities. This review emphasizes the benefits a proper hormonal balance during the different stages of life has in the CNS. To achieve this goal, it is essential that hormone levels are evaluated considering a woman's age and ovulatory status, so that a correct diagnosis and treatment can be made. Knowledge of steroid hormone activity in the brain will give women and health providers an important tool for improving their health and well-being.
The concept of the ovarian continuum can be understood as a process that occurs during a woman's lifetime and begins during intrauterine life with fertilization. Women start their reproductive years with approximately five hundred thousand follicles containing oocytes, of which only around five hundred will be released during ovulation. Ovulation has been recognized as an event linked with reproduction; however, recent evidence supports the role of ovulation as a sign of health. The use of biomarkers that help women recognize ovulation enables them to identify their health status. This knowledge helps medical healthcare providers in the prevention, diagnosis, and treatment of different pathologies related with endocrine disorders, gynecological abnormalities, autoimmune, genetic, and neoplastic diseases, as well as pregnancy-related issues. The knowledge of the ovarian continuum and the use of biomarkers to recognize ovulation should be considered a powerful tool for women and medical professionals.
The ovarian continuum is a process that occurs during a woman's lifetime. It begins during intrauterine life with fertilization and ends with menopause. This process can be greatly affected by different conditions such as changes in hormonal levels and illnesses. Therefore, understanding and promoting the knowledge and use of biomarkers of ovulation in women is a key aspect to consider when evaluating their health status. The knowledge and education about the ovarian continuum should be taken into account as a powerful tool for women and medical professionals.
Alvarado JL et al., 2016·Biomed Res Int·
Open Access
Delphinidin anthocyanins have previously been associated with the inhibition of glucose absorption. Blood glucose lowering effects have been ascribed to maqui berry (Aristotelia chilensis) extracts in humans after boiled rice consumption. In this study, we aimed to explore whether a standardized delphinidin-rich extract from maqui berry (Delphinol) affects glucose metabolism in prediabetic humans based on glycemia and insulinemia curves obtained from an oral glucose tolerance test (OGTT) after a challenge with pure glucose. Volunteers underwent four consecutive OGTTs with at least one week washout period, in which different doses of Delphinol were administered one hour before glucose intake. Delphinol significantly and dose-dependently lowered basal glycemia and insulinemia. Lower doses delayed postprandial glycemic and insulinemic peaks, while higher doses reversed this tendency. Glycemia peaks were dose-dependently lowered, while insulinemia peaks were higher for the lowest dose and lower for other doses. The total glucose available in blood was unaffected by treatments, while the total insulin availability was increased by low doses and decreased by the highest dose. Taken together, these open exploratory results suggest that Delphinol could be acting through three possible mechanisms: by inhibition of intestinal glucose transporters, by an incretin-mediated effect, or by improving insulin sensitivity.
This review explains the main effects exerted by sex steroids and other hormones on the adolescent brain. During the transition from puberty to adolescence, these hormones participate in the organizational phenomena that structurally shape some brain circuits. In adulthood, this will propitiate some specific behavior as responses to the hormones now activating those neural circuits. Adolescence is, then, a critical "organizational window" for the brain to develop adequately, since steroid hormones perform important functions at this stage. For this reason, the adolescent years are very important for future behaviors in human beings. Changes that occur or fail to occur during adolescence will determine behaviors for the rest of one's lifetime. Consequently, understanding the link between adolescent behavior and brain development as influenced by sex steroids and other hormones and compounds is very important in order to interpret various psycho-affective pathologies. Lay Summary : The effect of steroid hormones on the development of the adolescent brain, and therefore, on adolescent behavior, is noticeable. This review presents their main activational and organizational effects. During the transition from puberty to adolescence, organizational phenomena triggered by steroids structurally affect the remodeling of brain circuits. Later in adulthood, these changes will be reflected in behavioral responses to such hormones. Adolescence can then be seen as a fundamental "organizational window" during which sex steroids and other hormones and compounds play relevant roles. The understanding of the relationship between adolescent behavior and the way hormones influence brain development help understand some psychological disorders.
Hormones and Aging Tissues · Cardiometabolic Aging
Do the basal body temperature (BBT) shift and the cervical mucus markers for the beginning of the post-ovulatory infertile phase (POIP) of a menstrual cycle agree with the corresponding urinary pregnanediol glucuronide (PdG) threshold value? Perfect agreement between the cervical mucus markers and BBT shift and the hormonal definition of the start of post-ovulatory infertility occurred for only 7-17% of the cycles. The PdG threshold of 7.0 µmol/24 h is an objective and accurate marker for the beginning of the POIP. The rise in serum progesterone also produces the BBT shift and changes in cervical mucus which determine the mucus peak. Serum progesterone and urinary PdG are closely correlated when variations in urine volume are taken into account. STUDY DESIGN, SIZE, Individual menstrual cycle profiles of urinary PdG excretion rates for 91 fertile cycles from normally cycling women were analysed to identify the day of the beginning of the POIP. These days were compared with those determined by the day of the BBT shift +2 days, the day of the mucus peak +4 days and the later of these two indicators. The study lasted 3 years. PARTICIPANTS/MATERIALS, SETTING, A total of 62 women with normal menstrual cycles were recruited from three centres: Palmerston North, New Zealand; Sydney, Australia and Santiago, Chile. The cycles were displayed individually in a proprietary database program which recorded the PdG excretion rates, the BBT shift day and the cervical mucus peak day. A group of 15 women from a separate Chilean study had PdG urinary data measured as well as their day of ovulation determined by ultrasound. MAIN The BBT and cervical mucus markers differed significantly in their identification of the beginning of the POIP when compared with the PdG excretion rate of 7.0 µmol/24 h. The observation that the BBT shift day and the mucus peak day could be identified even though the PdG excretion rates were still at baseline levels in some cycles could lead to an unexpected pregnancy for women using these natural family planning (NFP) indicators. LIMITATIONS, The study consisted only of fertile cycles from women with regular cycles of 20-40 days duration. All the women were intending to avoid a pregnancy during the study, thus the limits of the fertile window were not tested. The NFP signals occurring earlier than the PdG threshold day could lead to an unexpected pregnancy. The signals occurring on the same day or later than the PdG threshold would not lead to unexpected pregnancies, but would require extra abstinence that could lead to non-compliance with the NFP method. A possible improvement in reliability of NFP methods is suggested. This study (project #90905) was funded by the NDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP). D.G.C. currently works for a diagnostic development company, Science Haven Ltd. The other authors have nothing to declare.
The onset of puberty has been a fascinating topic for reproductive endocrinologists for decades; however, its underlying physiological mechanisms have remained elusive until recently. The discovery and understanding of the effects exerted by the peptide hormone kisspeptin have shed light on this research area. This review is aimed to discuss the functions of kisspeptin, with special focus on its role in the onset of puberty and in the ovulatory mechanism. The points under discussion are (1) the characteristics of kisspeptin and its receptor, (2) the relevance of this hormone and its interaction with leptin in the onset of puberty, (3) the role of kisspeptin in the ovulatory mechanism based on its differential expression at hypothalamic nuclei, which is modulated by sex steroid hormones, and (4) the clinical relevance of kisspeptin and its antagonists in new therapeutic strategies for the treatment of various reproductive pathologies. All of this explains the revolution that kisspeptin has caused among researchers working in the field of gynecological endocrinology and reproductive biology.
To assess the sensitivity and specificity of the self-identified fertile window. Observational study. Not applicable. PATIENT(S): A total of 107 women. INTERVENTION(S): Women recorded cervical mucus observation and basal body temperature daily while undergoing daily ovarian ultrasound. MAIN OUTCOME MEASURE(S): The biological fertile window, defined as the 6 days up to and including the day of ovulation; and the 2-day ovulation window, defined as the day before and the day of ovulation. RESULT(S): The self-identification of the biological fertile window by the observation of any type of cervical mucus provides 100% sensitivity but poor specificity, yielding a clinical fertile window of 11 days. However, the identification of the biological fertile window by peak mucus (defined as clear, slippery, or stretchy mucus related to estrogen) yielded 96% sensitivity and improved specificity. The appearance of the peak mucus preceded the biological fertile window in less than 10% of the cycles. Likewise, this type of mucus identified the ovulation window with 88% sensitivity. CONCLUSION(S): These results suggest that, when perceived accurately, more accurate clinical self-detection of the fertile window can be obtained by identification of peak mucus. This may improve efforts to focus intercourse in the fertile phase for couples with fertility concerns.
The objective of this editorial is to show that a harmonious relationship between science and faith is possible, as exemplified by great saints of the Catholic Church. It begins with the definitions of science and faith, followed by an explanation of the apparent conflict between them. A few saints that constitute an example that a fruitful relationship between these two seemingly opposed realities has been possible are Saint Albert the Great, Saint John of the Cross, Saint Giuseppe Moscati, and Saint Edith Stein, among others, and this editorial highlights their deep contributions to the dialogue between faith and reason. This editorial ends with a brief discussion on whether it is possible to be both a scientist and a man of faith.
What are the characteristics of, and how variable are, individual normal menstrual cycle profiles of excretion rates for the urinary metabolites oestrone glucuronide (E1G) and pregnanediol glucuronide (PdG)? There is a continuum of menstrual cycle profiles that differ from standard textbook profiles but which can be understood simply in terms of growth, atresia and ovulation of ovarian follicles. Point-of-care assays with the Ovarian Monitor pre-coated assay tubes, using urine samples diluted to a constant volume per unit time, give laboratory accurate clinical data for individual menstrual cycles. Lay operators can perform the point-of-care assay system at home to achieve reliable and reproducible results, which can be used for natural family planning. STUDY DESIGN, SIZE, This prospective study involved 62 women, with normal menstrual cycles, recruited from three centres: Palmerston North, New Zealand, Sydney, Australia and Santiago, Chile. The study lasted 3 years. PARTICIPANTS/MATERIALS, SETTING, Women collected daily urine samples and determined their E1G and PdG rates with a pre-coated enzyme assay system known as the Ovarian Monitor. For two cycles, the assays were repeated in a study centre and the results were averaged to give 113 individual menstrual cycles for analysis. The cycles were displayed individually in a proprietary database program. MAIN The individual normal hormonal profiles were more complex than the classic composite curves for 40% of the cycles. Of 113 ostensibly normal cycles, only 91 were potentially fertile and 22 had some luteal phase defect. The oestrone glucuronide and PdG excretion rates were reliable and informative in the non-invasive elucidation of ovulation and ovarian function for both simple and complex profiles. Daily monitoring revealed the variability of normal menstrual cycle profiles. The LH peaks were variable and ambiguous markers for ovulation. LIMITATIONS, The study consisted of cycles only from women with regular cycles of 20-40 days duration. All the women were intending to avoid a pregnancy during the study thus the limits of the fertile window were not tested. The principles established in this study should apply to cycles of any length. All peaks in oestrone glucuronide excretion should be tested by concurrent measurements of PdG, which gives a positive indication of the fate of the follicle it represents. The Ovarian Monitor provides a useful addition for practitioners of natural family planning. STUDY FUNDING/COMPETING INTEREST(S): Financial support for this study was obtained from the UNDP/UNFPA/World Bank/WHO Special Programme of Research, Development and Research Training in Human Reproduction (HRP). D.G.C. is currently employed by and holds stock in Manawatu Diagnostics Ltd, a company in the development phase of a potentially competing product. The remaining authors have nothing to declare.
Fertility awareness constitutes fundamental knowledge for every woman and is an important tool for health professionals. The objective of this review is to show how fertility awareness can be useful in the assessment of a woman's health. The main techniques for detecting ovulation are explained, and then the events that characterize a normal menstrual cycle are discussed. The relevance of cervical mucus from the perspective of female fertility is highlighted. Finally, the usefulness of fertility awareness 1) to identify fertile and infertile periods, 2) to help to detect several pathologies, and 3) in regards to how it exerts an important role in the success of programs in education for affectivity and sexuality are discussed.
The oviduct is an important organ for successful mammalian reproduction. In this work, human oviducts were inseminated and their explants analyzed using scanning electron microscopy in order to study, at a finer ultrastructual level, the interaction between spermatozoon and oviduct in vitro. Results show unequivocally a spermatozoon tightly attached through the acrosomal region of its head to several cilia of the human tubal epithelial cells. This finding proves that spermatozoa do indeed adhere to the endosalpinx, a fact of utmost relevance for the physiology of the reproductive process, since it supports the idea of a spermatozoa reservoir being formed in the oviduct, which is also briefly discussed.
The UNDP/WHO/World Bank/Special Programme of Research, Development and Research Training in Human Reproduction (Geneva) set up a study to determine whether it is feasible for women to monitor their ovarian activity reliably by home testing. Daily self-monitoring of urinary hormone metabolites for menstrual cycle assessment was evaluated by comparison of results obtained with the Home Ovarian Monitor by untrained users both at home and in study centres. Women collected daily data for urinary estrone glucuronide (E1G) and pregnanediol glucuronide (PdG) for two cycles, then the procedure was repeated in the women's local centre (in Chile, Australia or New Zealand) giving a total of 113 duplicate cycles. The tests were performed without the benefit of replicates or quality controls. The home and centre cycles were normalized and compared to identify assay errors, and the resulting home and centre menstrual cycle profiles were averaged. Reliable mean cycle profiles were obtained with the home and centre excretion rates agreeing to within 36 ± 21 nmol/24 h for E1G and 0.77 ± 0.28 µmol/24 h for baseline PdG values (1-5 µmol/24 h). The cycles had a mean length of 28.1 ± 3.1 days (n = 112; 5th and 95th percentiles: 24 and 35 days, respectively), a mean follicular phase of 14.8 ± 3.1 days (n = 107; 5th and 95th percentiles: 11 and 21 days) and a mean luteal phase length of 13.3 ± 1.5 days (n = 106; 5th and 95th percentiles: 11 and 17 days), calculated from the day of the LH peak. The study confirmed that the Ovarian Monitor pre-coated assay tubes worked well even in the hands of lay users, without standard curves, quality controls or replicates. Point-of-care monitoring to give reliable fertility data is feasible.
Neurophysiological and behavioral development is particularly complex in adolescence. Youngsters experience strong emotions and impulsivity, reduced self-control, and preference for actions which offer immediate rewards, among other behavioral patterns. Given the growing interest in endocrine effects on adolescent central nervous system development and their implications on later stages of life, this article reviews the effects of gonadal steroid hormones on the adolescent brain. These effects are classified as organizational, the capacity of steroids to determine nervous system structure during development, and activational, the ability of steroids to modify nervous activity to promote certain behaviors. During transition from puberty to adolescence, steroid hormones trigger various organizational phenomena related to structural brain circuit remodelling, determining adult behavioral response to steroids or sensory stimuli. These changes account for most male-female sexual dimorphism. In this stage sex steroids are involved in the main functional mechanisms responsible for organizational changes, namely myelination, neural pruning, apoptosis, and dendritic spine remodelling, activated only during embryonic development and during the transition from puberty to adolescence. This stage becomes a critical organizational window when the appropriately and timely exerted functions of steroid hormones and their interaction with some neurotransmitters on adolescent brain development are fundamental. Thus, understanding the phenomena linking steroid hormones and adolescent brain organization is crucial in the study of teenage behavior and in later assessment and treatment of anxiety, mood disorders, and depression. Adolescent behavior clearly evidences a stage of brain development influenced for the most part by steroid hormones.
Male Endocrine and Genetic Factors · Male Hormonal Axis
Spermatozoon acrosome reaction is an exocytotic event of the utmost importance for the development of mammalian fertilisation. Current evidence shows that the triggering of the acrosome reaction (AR) could be regulated by the action of diverse compounds, namely, metabolites, neurotransmitters and hormones. The aim of the present review is to describe the modulating effects of several compounds that have been classified as inductors or inhibitors of acrosome reaction. Among AR inductors, it is necessary to mention progesterone, angiotensin II, atrial natriuretic peptide, cathecolamines, insulin, leptin, relaxin and other hormones. Regarding the inhibitors, oestradiol and epidermal growth factor are among the substances that retard AR. It is worth mentioning that gamma-aminobutyric acid, a neurotransmitter known to be an inhibitor in the central nervous system, has been shown to induce AR. The multiple hormones located in the fluids of the female reproductive tract are also likely to act as subtle regulators of AR, constituting a fundamental aspect for the development of successful fertilisation. Finally, it is necessary to emphasise that the study of regulation exerted by hormones and other compounds on AR is essential for further understanding of mammalian reproductive biology, especially spermatozoon physiology.
Two types of cervical mucus are recognized, oestrogenic and gestagenic. These are constituted by different subtypes, and their characteristics change depending on variations in the hormonal levels and on the existence of several pathologies. Our aim was to identify the ultrastructure and crystallization characteristics of the cervical mucus in women suffering from polycystic ovary syndrome, and to compare these characteristics with those of normal control women. Cervical mucus samples were taken from 10 women, 4 control group women (with normal ovulatory menstrual cycles) and 6 suffering from polycystic ovary syndrome (2 with ovulatory and 4 with anovulatory cycles). This mucus was characterized according to its ultrastructure and crystallization. The type of mucus obtained was related to the levels of oestradiol and progesterone present when the samples were taken. As regards mucus ultrastructure, differences were found between the control women and those with polycystic ovary syndrome and anovulatory menstrual cycles. Such variations were evident in the type of mesh and the average diameter of the mucus pores. Mucus crystallization in control women showed the usual oestrogenic disposition: fern-like (L, P2), rectilinear (S) or a hexagonal structure (P6). On the other hand, in women with polycystic ovary syndrome, indefinite mucus crystallizations were found, as well as crystallization patches resembling oestrogenic and gestagenic-like mucus. This study shows that the ultrastructure and crystallization characteristics of the cervical mucus in polycystic ovary syndrome women are different from those of control women. The latter would be dependent on their levels of oestradiol and progesterone.
Male Endocrine and Genetic Factors · Male Hormonal Axis
The acrosome is a secretory vesicle located in the sperm head. The acrosome reaction consists in the fusion of the sperm plasma membrane with the external acrosomal membrane. It has been observed that this reaction does not take place in spermatozoa incubated in cervical mucus, hydrogel that contains high concentrations of oestradiol in the peri-ovulatory period. The objective of the present study was to analyse the influence of oestradiol on the acrosome reaction in human spermatozoa to evaluate the possible inhibitory effect of this hormone. Spermatozoa were incubated in progesterone (10.1 nmol l(-1)); oestradiol plus progesterone (oestradiol at 840 pmol l(-1) and progesterone at 10.1 nmol l(-1)), oestradiol (840 pmol l(-1)) and control (without steroidal hormones) for 30 min, 60 min, 240 min and 24 h. The acrosome reaction was evaluated by stain with Hoechst 33258 and fluorescein isothiocyanate-conjugated Pisum sativum agglutinin lectin. Progesterone-incubated spermatozoa showed the highest percentage of acrosome reaction (P < 0.05). Spermatozoa incubated with oestradiol and oestradiol plus progesterone showed the lowest percentage of acrosome reaction. The present study demonstrates the inhibitory role of oestradiol on the acrosome reaction, stimulated by progesterone in human spermatozoa under physiological conditions.
Thyroid and Metabolic Function · Insulin and Metabolism
Polycystic ovary syndrome (PCOS) is non-uniformly associated with insulin resistance (IR). We examined IR in women with PCOS. Sixty-nine PCOS women were subjected to the insulin suppression test (IST) to determine their steady-state plasma glucose (SSPG) as a direct measure of insulin sensitivity. SSPG exhibited a multimodal distribution suggesting the existence of subpopulations. The heterogeneous distribution of plasma glucose at 180 min (P = 0.011), with three modes, suggested differences in the plasma glucose level trajectories during the IST. Hence, the population was separated into three groups: (i) (n = 33), subjects with SSPG < or = 152.5 mg/dl, corresponding to the first to fifth deciles; (ii) (n = 29), subjects in the interval 152.5 mg/dl < SSPG < or = 300 mg/dl; (iii) (n = 7), subjects with SSPG > 300 mg/dl, corresponding to the tenth decile. Plasma glucose distributions at 180 min showed differences in their mean values and ranges among groups (P < 0.0001). The trajectories of the groups differed significantly during the IST (P < 0.0001). insulin sensitivity in our patients exhibited a discontinuous distribution, implying that PCOS is a heterogeneous disorder possessing subpopulations regarding IR.
The concept of the ovarian cycle as a continuum considers that all types of ovarian activity encountered during the reproductive life are responses to different environmental conditions in order to ensure the health of the woman. During the normal ovulatory cycle, a series of sequential events have to occur in a highly synchronized manner. Fertility awareness is useful in helping women to identify the different stages of their reproductive life cycle. Fertility awareness is also a valuable tool in helping women to identify gynecological disorders. Persistence of irregularities within the mucus patterns and the menstrual cycle should be of concern to women presenting with these problems. These irregularities may be due to obstetrical, endocrine, gynecological or iatrogenic disorders. Insight into early pregnancy complications, ovulatory dysfunction and pelvic inflammatory disease can be ascertained from abnormalities within the menstrual cycle and mucus pattern. Thus, fertility awareness will also enable the recognition and early treatment of several metabolic, endocrine and infectious diseases.
Urgent measures are required to stop the increase in the frequency of pregnancies and sexually transmitted diseases among teenagers. A means of facing this problem is promoting sexual abstinence among youngsters. There are studies that confirm the efficacy of this approach. To show the results of the application of a holistic sexuality program (TeenSTAR) among Chilean teenagers. Students attending basic or high school were divided into a control or study group. The control group (342 students) received the usual education on sexuality given by their schools and the study group (398 students) participated in twelve TeenSTAR sessions lasting 1.5 hours each, given by a trained professor. Assessment of achievements was made using an anonymous questionnaire answered at the start and end of the program. The rates of sexual initiation among control and study groups were 15 and 6.5%, respectively. Among sexually active students, 20% of those in the study group and 9% of those in the control group discontinued sexual activity. A higher proportion of students in the TeenSTAR program retarded their sexual initiation or discontinued sexual activity and found more reasons to maintain sexual abstinence than control students.
Estrogen and progestin combination in hormone replacement therapy (HRT) increases the incidence of breast cancer, but decreases the endometrial cancer risk of unopposed estrogen. Therefore, a SERM such as Tibolone, that delivers the beneficial, but not the adverse side effects, of steroid hormones would be clinically advantageous. However, data from the Million Women Study suggests that Tibolone increases the risk of both breast and endometrial cancer. Herein, we assessed the estrogenic and progestagenic actions of Tibolone using transvaginal sonography studies and an in vitro model of breast (ZR-75, MCF7) and endometrial cancer (Ishikawa). The known cancer associated proteins (ER, EGFR, STATS, tissue factor and Bcl-xL) were selected for study. Transvaginal sonography demonstrated that postmenopausal women treated with Tibolone displayed a thinner endometrium than in the late proliferative phase, but had a phenotype characteristic of the secretory phase, thus demonstrating the estrogenic and progestagenic actions of this SERM. In vitro, Tibolone acted as an estrogen in downregulating ER and upregulating Bcl-xL, yet as progesterone, increasing STAT5 and tissue factor in breast cancer cells. The increase in tissue factor by Tibolone correlated with its coagulative potential. Interestingly, EGFR was up-regulated by progesterone in the breast and by estrogen in endometrial cells, while Tibolone increased protein levels in both cell types. In conclusion, this study further demonstrates the estrogenic and progestagenic nature of Tibolone. The pattern of regulation of known oncogenes in cells of breast and endometrial origin dictates caution and vigilance in the prescription of Tibolone and subsequent patient monitoring.
Two main types of cervical mucus have been described during the menstrual cycle: oestrogenic and progestative. Each category shows diverse morphological and functional features from the reproductive point of view. Traditionally, this change has been approached by analysing morphological patterns. In fact, a mesh model has been described for cervical mucus, structurally composed of fibrillar subunits with a parallel orientation, together with another model in a characteristic network shape with canalicular units, but the real model is not clear. The objective of our work was to study the different morphological structures of the mucus, as related to the day of follicular rupture (considered as day 0) determined by ultrasound. Cervical mucus samples were obtained from the cervical canal with an ASPIRETTEtrade mark from day -4 to day +1 of the menstrual cycle. Samples were fixed and dried by critical point. The ultrastructure was examined with scanning electron microscopy. The presence of three types of oestrogenic and one type of progestative cervical mucus was confirmed in this period. Our paper shows different types of ultrastructure in the oestrogenic mucus in relation to ovulation, which would help to understand the interaction between male gametes and cervical mucus in migration through the female genital tract.
To evaluate the efficacy of an abstinence-centered sex education program in adolescent pregnancy prevention, the TeenSTAR Program was applied in a high school in Santiago, Chile. A total of 1259 girls from a Santiago high school were divided into three cohorts depending on the year they started high school: the 1996 cohort of 425 students, which received no intervention; the 1997 cohort, in which 210 students received an intervention and 213 (control group) did not; and the 1998 cohort, in which 328 students received an intervention and 83 (control group) did not. Students were randomly assigned to control and intervention groups in these cohorts, before starting with the program. We conducted a prospective, randomized study using the application of the TeenSTAR sex education program during the first year of high school to the intervention groups in the 1997 and 1998 cohorts. All cohorts were followed up for 4 years; pregnancy rates were recorded and subsequently contrasted in the intervention and control groups. Pregnancy rates were measured and Risk Ratio with 95% confidence interval were calculated for intervention and control groups in each cohort. Pregnancy rates for the intervention and control groups in the 1997 cohort were 3.3% and 18.9%, respectively (RR: 0.176, CI: 0.076-0.408). Pregnancy rates for the intervention and control groups in the 1998 cohort were 4.4% and 22.6%, respectively (RR 0.195, CI: 0.099-0.384). The abstinence-centered TeenSTAR sex education intervention was effective in the prevention of unintended adolescent pregnancy.
Measurement and Statistics · Instrument Development and Validation
A study was conducted to determine the accuracy and reliability of the Home Ovarian Monitor for measuring estrone glucuronide (E1G) and pregnanediol glucuronide (PdG) during ovulatory cycles as a means of monitoring ovarian activity. Approximately 60 ovulating women in three centres collected timed specimens of urine (3h or more) for a total of six cycles each. The women measured the E1G and PdG excretion per 24h in their urine specimens using the Monitor. A local laboratory using the Monitor also measured the excretion. Urine specimens from 18 to 19 cycles were sent frozen to the WHO Reference Laboratory in London where they were analysed for E1G and PdG by the Monitor and by radioimmunoassay (RIA). The correlation coefficients between the Monitor and radioimmunoassay results obtained in London were better than 0.84 in 80% of the cycles. A urine bias caused the Monitor E1G results to be higher than those obtained by radioimmunoassay but the daily patterns were the same. In 50% of the cycles, this bias caused a delay of up to 3 days in identifying the beginning of the E1G rise compared with radioimmunoassay. Timing of the preovulatory E1G peak and the postovulatory PdG rise agreed within the experimental errors of the two systems. The study confirmed that women using the Monitor at home obtained results that were as accurate as those obtained by laboratory procedures. Careful supervision was required to maintain laboratory levels of quality control and interpretation of results.
The incidence of Chlamydia trachomatis (Ct) infection and the possible correlation between couples presenting with first-trimester spontaneous abortions and active Ct infection was assessed. Additionally, the ability of Ct to infect zona-free hamster oocytes was explored by incubating the oocytes with spermatozoa from infected patients. A total of 961 women and 750 men consulting our reproductive medicine centre were screened for Ct using direct immunofluorescence. The general incidence of Ct infection was 9.4% in females (90 of 961) and 13.9% in males (104 of 750). In women with spontaneous abortions the incidence of Ct was 21.0% (14 of 66) compared with 8.9% (23 of 59) for women without spontaneous abortions and term pregnancies (chi-square, P < 0.05). When both partners of the couples were considered (one or both partners infected), the incidence rose to 68.8% (22 of 32) (chi-square, P < 0.001). In vitro studies using electron microscopy demonstrated the presence of Ct on the surface of and inside the oocyte. These results indicate a correlation between an active Ct infection and spontaneous abortion. Electron microscopy studies suggested the possibility of direct oocyte infection by Ct. Two models are proposed for the pathogenesis of Ct-related early abortions: (i) direct zygote infection, and (ii) immune response to heat shock proteins expressed by the zygote and triggered by previous Ct infections.
The mechanism by which GnRH increases sperm-zona pellucida binding in humans was investigated in this study. We tested whether GnRH increases sperm-zona binding in Ca(2+)-free medium and in the presence of Ca(2+) channel antagonists. We also examined the GnRH effect on the intracellular free Ca(2+) concentration ([Ca(2+)](i)). Sperm treatment with GnRH increased sperm-zona binding 300% but only when Ca(2+) was present in the medium. In Ca(2+)-free medium or in the presence of 400 nM nifedipine, 80 microM diltiazem, or 50 microM verapamil, GnRH did not influence sperm-zona binding. GnRH increased the [Ca(2+)](i) in the sperm in a dose-dependent manner. The maximum effect was reached with 75 nM GnRH. The GnRH-induced increase in [Ca(2+)](i) was fast and transient, from a basal [Ca(2+)](i) of 413 +/- 22 nM to a peak value of 797 +/- 24 nM. The GnRH-induced increase in [Ca(2+)](i) was entirely due to a Ca(2+) influx from the extracellular medium because the increase in [Ca(2+)](i) was blocked by the Ca(2+) chelator EGTA and by the Ca(2+) channel antagonists nifedipine and diltiazem. These antagonists, however, were not able to inhibit the progesterone-activated Ca(2+) influx. On the contrary, T-type calcium channel antagonists pimozide and mibefradil did not affect GnRH-activated Ca(2+) influx but inhibited the progesterone-activated Ca(2+) influx. Finally, the GnRH-induced Ca(2+) influx was blocked by two specific GnRH antagonists, Ac-D-Nal(1)-Cl-D-Phe(2)-3-Pyr-D-Ala(3)-Arg(5)-D-Glu(AA)(6)-GnRH and Ac-(3,4)-dehydro-Pro(1),-p-fluoro-D-Phe(2), D-Trp(3,6)-GnRH. These results suggest that GnRH increases sperm-zona binding via an elevation of [Ca(2+)](i) through T-type, voltage-operated calcium channels.
During lactational amenorrhea a special type of cervical mucus, similar to that found during the luteal phase, is produced. This mucus, however, is able to support sperm migration. In the study described, the ability of spermatozoa to bind to the human zona pellucida (hZP) after migration through periovulatory and post-partum mucus was studied. Mucus was obtained from exclusively breastfeeding women in amenorrhea at 30, 60, 120 and 180 days post-partum. Periovulatory mucus samples from normally cycling women were used as a control. Flat capillary tubes were filled with BWW culture medium at the top and cervical mucus at the bottom. The tubes were immersed in a semen reservoir and the spermatozoa allowed to migrate through the mucus for 3 h into the culture media. Then the spermatozoa were coincubated with 3-4 hZP for 30 min and the number of bound spermatozoa per zona was counted. Periovulatory cervical mucus had an average Insler score of 14 +/- 0.5 as compared to 4.6 +/- 0.4 for post-partum mucus. Spermatozoa recovered from periovulatory mucus were always able to bind to the hZP in only 68 +/- 7% of the cases. Moreover, spermatozoa recovered from post-partum mucus bound to the ZP in lower numbers than did spermatozoa recovered fro periovulatory mucus (p < 0.03). These results suggest a greater ability of sperm-hZP binding after migration through periovulatory mucus and they also indicate that sperm binding to the ZP is possible even after sperm migration through a low quality mucus.
The sperm function of fertile men (control), infertility patients (experimental), and men with varicocele were compared. The bioassays used were the follicular fluid-induced acrosome reaction, the binding to the zona pellucida, and the penetration of zona-free hamster oocytes. The percentage (mean +/- SEM) of reacted spermatozoa was 35 +/- 3 in the control, 22 +/- 1 in the experimental, and 22 +/- 3 in the varicocele. The minimum value of acrosome reaction in control men was 20%. The mean number of zona-bound spermatozoa was 250 +/- 30 in the control, 160 +/- 28 in the experimental, and 196 +/- 44 in the varicocele. The minimum number of zona bound spermatozoa in control men was 50. The mean number of hamster oocytes penetrated was 50 +/- 8 in the control, 19 +/- 3% in the experimental, and 10 +/- 3 in the varicocele. The minimum number of oocytes penetrated in control men was 6%. In the experimental group, 22 men had a normal sperm function, 58 had 1 or 2 bioassays below the minimum (relative dysfunction), and 10 had all bioassay below the minimum (abnormal sperm function). The results of these bioassays could help to reclassify the infertile men in several subgroups.
Cervical mucus is produced throughout the menstrual cycle. Sperm migration, however, is possible only during the periovulatory period of the cycle. Cervical mucus is also produced during the amenorrhoeic post-partum period. Post-partum mucus is very similar to luteal phase mucus except that it can allow sperm migration. In this study, mucus samples obtained from all these periods were classified according to their capacity to allow sperm migration. The biochemical characteristics of mucus samples that did (peri-ovulatory and 40% of post-partum samples) and did not (luteal and 60% of post-partum samples) allow sperm migration were then compared. Mucus samples with positive sperm migration showed the highest percentage of water and lowest protein and glycoprotein concentration (per ml of mucus). In addition, post-partum mucus samples with positive sperm migration showed lower concentrations of proteins and glycoproteins than post-partum mucus samples that did not allow sperm migration. However, the amount of glycoproteins per mg of protein was similar between post-partum samples that were positive and negative for sperm migration. These data suggest that the carbohydrate composition of the glycoproteins is playing a key role in the ability of cervical mucus to accept spermatozoa.
In this study we have evaluated the score, sperm migration and ultrastructural characteristics of cervical mucus present in amenorrhoeic women under exclusive breastfeeding at 30, 60, 90, 120, 150 and 180 days post-partum. Periovulatory mucus samples from seven normally cycling women were used as a control. The average scores of post-partum and periovulatory mucus were 4.6 +/- 0.4 and 14.1 +/- 0.5 respectively. Twenty-one (39%) of the 54 post-partum cervical mucus samples and all (100%) periovulatory mucus samples allowed sperm migration. Positive sperm migration into post-partum mucus was observed at all time intervals studied. The only parameter that correlated with sperm migration into post-partum mucus was ferning formation. Sperm migration was obtained in all post-partum mucus samples with a score greater than 8, but samples with scores between 2 and 7 also showed sperm penetration. Scanning electron microscopic studies showed the characteristic spongy appearance of periovulatory mucus. Post-partum mucus was formed by a dense mesh (rocky appearance), when samples were generally unable to sustain sperm migration, but samples where sperm migration occurred showed small areas of spongy mucus mixed with areas in which a dense mesh and high cellularity was observed.
Anti-Infective and Anti-Inflammatory Agents · Antibiotics in Reproductive Care
Mollicutes are frequently isolated from sperma of infertile men. The potential effect on the fertility of mollicute infection is controversial as is antibiotic therapy. In our andrological patients, the prevalence of mollicutes is approximately 10%. To evaluate the benefit of antibiotic therapy, we investigated two groups of group 1-patients with positive or negative mollicute cultures and normal spermiogram; morphological changes on spermatozoa were particularly evaluated (n = 40); group 2 - patients with positive mollicute cultures treated with doxycycline or erythromycin. Sperm parameters were analysed before and after treatment (n = 20). When infected and non-infected sperma from group 1 were compared, the only difference found was an alteration of the sperm tail (p less than 0.005). Light microscopy and electron microscopy (EM) often revealed coiled tails which were probably due to adhesion of mollicutes (EM). The most frequently observed pathology in group 2 was found in patients with teratoasthenozoospermia. Compared with the post-therapy spermiogram, a significant difference was only observed in spermatozoal morphology (p less than 0.005). Therefore, we conclude that mollicutes produce important alterations in the human spermatozoal morphology, especially in the tail which appears in a spiral form. Since teratozoospermia is considered to be an important factor of infertility in man, antibiotic therapy is recommended in cases of mollicute involvement.
Mammalian spermatozoa must undergo many changes to be able to fertilize the oocyte. One of these changes, the acrosome reaction, has been established as a requisite for gamete membrane fusion to occur; it consists of the fusion and vesiculation of the sperm plasma membrane with the outer acrosomal membrane of the principal segment of the acrosome. Reaction of the equatorial segment has occasionally been observed. The objective of the present work was to determine whether the presence of the sperm plasma membrane over the equatorial segment is necessary for gamete membrane fusion to occur. Golden hamster spermatozoa were capacitated in vitro in TAPL 10K, and the maximum possible percentage of acrosome reaction was determined at 82.79% + 1.69% SD (P = 0.27; r = 0.21). Ultrastructural studies showed that 93.6% of the reacted spermatozoa in this population had their principal and equatorial segments reacted. The fertilizing ability of these spermatozoa was assayed using zona-free hamster oocytes. The percentage of fertilized ova obtained was 98.8% (308/312). Ultrastructural studies showed the presence of spermatozoa with reacted equatorial segment inside the cytoplasm of immature oocytes. The evidence presented in this work demonstrates that the plasma membrane of spermatozoa with reacted equatorial segment retains its ability to fuse with the oocyte.
Samples of semen and cervical mucus were provided by 18 couples. Cervical mucus was obtained for each day possible and stored at 4 degrees C until all the samples were collected. Flat capillary tubes were loaded with the mucous samples and spermatozoa from the husband's semen sample were allowed to migrate through the cervical mucus (3 cm column) into culture medium. The spermatozoa recovered after migration through cervical mucus were assayed in vitro with zona-free hamster oocytes. Control experiments were carried out using spermatozoa from the same semen sample but prepared by the swimming-up technique. Altogether, 557 eggs in the control group and 1236 eggs in the experimental group were analysed, and the results demonstrated that the % of sperm penetration, the mean number of sperm decondensations per penetrated egg and the mean number of spermatozoa adhering per egg all had higher values (P less than 0.05) for the control samples than for the experimental samples. We suggest that cervical mucus modifies human spermatozoa, as measured by their interaction with zona-free hamster oocytes.
Human cervical mucus from women using Lippes Loop and T-Cu-200 IUDs was used to study sperm migration in vitro using flat capillary tubes. Cervical mucus from women bearing no IUD was used as the control. 100% of the control samples, 83% of the Lippes Loop users, and 88% of the T-Cu-200 users had more than 100 spermatozoa/field of 100x. In 17% and in 11% there were between 40 and 100 spermatozoa/field of 100x in the Lippes Loop and T-Cu-200 users. The presence of copper IUDs does not interfere with sperm migration in vitro through human cervical mucus.
The important role of cervical mucus from a reproduction standpoint is the transport and selection of spermatozoa. The study of the fertilizing ability of human spermatozoa by the use of zona-free hamster oocytes has shown that morphologically abnormal sperm can fuse with the zona-free hamster oocyte. The high proportion of morphologically abnormal spermatozoa present in human semen is significantly reduced after sperm migration through cervical mucus. The mucus, while a favorable environment for sperm survival, does not seem to contribute to the occurrence of sperm capacitation and acrosome reaction.