Sumigama, S., Mansell, S., Miller, M., Lishko, P. V., Cherr, G. N., Meyers, S. A., & Tollner, T. (2015). Progesterone Accelerates the Completion of Sperm Capacitation and Activates CatSper Channel in Spermatozoa from the Rhesus Macaque. Biology of reproduction. https://doi.org/10.1095/biolreprod.115.129783
Sumigama S, Mansell S, Miller M, Lishko PV, Cherr GN, Meyers SA, Tollner T. Progesterone Accelerates the Completion of Sperm Capacitation and Activates CatSper Channel in Spermatozoa from the Rhesus Macaque. Biology of reproduction. 2015. doi:10.1095/biolreprod.115.129783
Sumigama, S., et al. "Progesterone Accelerates the Completion of Sperm Capacitation and Activates CatSper Channel in Spermatozoa from the Rhesus Macaque." Biology of reproduction, 2015.
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RRM Academy Synopsis
Progesterone speeds up capacitation in macaque sperm in vitro
A lab study of sperm from five adult male rhesus macaques found that progesterone primes sperm to complete the acrosome reaction at the egg's outer coat. At the highest exposures, about 1 out of 10 sperm became fully hyperactive. The sperm carried a progesterone-sensitive CatSper calcium channel, as human sperm do.
Key Findings
Recordings from three macaque sperm cells showed CatSper currents that all three cells raised with progesterone: an average 2-fold rise in outward current, against a 2.7-fold rise reported for human sperm.
In dish experiments, progesterone significantly raised the share of sperm completing the zona pellucida-induced acrosome reaction. Sperm without a zona showed no progesterone-driven acrosome reaction at the levels tested.
Fully hyperactivated motility reached 8.7 ± 2.6% and 9.9 ± 2.5% of sperm at the two highest exposures. Lateral head displacement rose with dose; velocity differences were not significant pairwise.
Sperm protein tyrosine phosphorylation did not change with progesterone in these experiments, and the number of sperm binding the zona pellucida did not differ with treatment.
Interpretation
This is a basic-science experiment on washed macaque sperm in a dish, using five males and a medium built to resemble fluid around ovulation. The study had no women or men, no pregnancies and no fertility outcomes. Progesterone levels inside the living oviduct are hard to measure. The authors call their exposures physiologic estimates. Their account of how sperm behave near the egg is a proposal, and they say single-sperm calcium studies are needed to test it.
RRM Context
Progesterone reaches the egg's surroundings because ovulation occurred, so a healthy ovulatory event sends a signal that sperm respond to. The macaque work fits a couple-level view of fertility, where the male partner's sperm meet the woman's cycle. Restorative reproductive medicine treats both as part of one clinical question.
Our editorial summary of this paper, not the article's abstract.
Abstract
During transit through the female reproductive tract, mammalian spermatozoa are exposed to increasing concentrations of progesterone (P4) released by the cumulus oophorus. P4 triggers massive calcium influx into human sperm through activation of the sperm-specific calcium channel CatSper. These properties of human spermatozoa are thought to be unique since CatSper is not progesterone sensitive in rodent sperm. Here, by performing patch clamp recording from spermatozoa from rhesus macaque for the first time, we report that they express P4-sensitive CatSper channel identically to human sperm and react to P4 by inducing responsiveness to zona pellucida, unlike human sperm, which respond directly to P4. We have also determined the physiologic levels of P4 capable of inducing capacitation-associated changes in macaque sperm. Progesterone (1 μM) induced up to a 3-fold increase in the percentage of sperm undergoing the zona pellucida-induced acrosome reaction with the lowest threshold as low as 10 nM of P4. Submicromolar levels of P4 induced a dose-dependent increase in curvilinear velocity and lateral head displacement, while sperm protein tyrosine phosphorylation was not altered. Macaque spermatozoa exposed to 10 μM of P4 developed fully hyperactivated motility. Similar to human sperm, on approaching cumulus mass and binding to zona pellucida, macaque spermatozoa display hyperactivation and undergo an acrosome reaction that coincides with the rise in the sperm intracellular calcium. Taken together, these data indicate that P4 accelerates the completion of capacitation and provides evidence of spermatozoa "priming" as they move into a gradient of progesterone in search for the oocyte.
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.
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.
Dcunha R et al., 2022·Reproductive sciences (Thousand Oaks, Calif.)·Free full text on PubMed Central
Spermatozoon is a motile cell with a special ability to travel through the woman's reproductive tract and fertilize an oocyte. To reach and penetrate the oocyte, spermatozoa should possess progressive motility. Therefore, motility is an important parameter during both natural and assisted conception. The global trend of progressive reduction in the number and motility of healthy spermatozoa in the ejaculate is associated with increased risk of infertility. Therefore, developing approaches for maintaining or enhancing human sperm motility has been an important area of investigation. In this review we discuss the physiology of sperm, molecular pathways regulating sperm motility, risk factors affecting sperm motility, and the role of sperm motility in fertility outcomes. In addition, we discuss various pharmacological agents and biomolecules that can enhance sperm motility in vitro and in vivo conditions to improve assisted reproductive technology (ART) outcomes. This article opens dialogs to help toxicologists, clinicians, andrologists, and embryologists in understanding the mechanism of factors influencing sperm motility and various management strategies to improve treatment outcomes.
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.
Male Fertility › Male Endocrine and Genetic Factors › Male Hormonal Axis · Reproductive Endocrinology › Ovarian Hormones › Progesterone
Melissa Miller
M Miller
PMID 26490839 26490839 DOI 10.1095/biolreprod.115.129783 10.1095/biolreprod.115.129783 Sumigama et al. 2015, Sumigama 2015
Cite this article
Sumigama, S., Mansell, S., Miller, M., Lishko, P. V., Cherr, G. N., Meyers, S. A., & Tollner, T. (2015). Progesterone Accelerates the Completion of Sperm Capacitation and Activates CatSper Channel in Spermatozoa from the Rhesus Macaque. Biology of reproduction. https://doi.org/10.1095/biolreprod.115.129783
Sumigama S, Mansell S, Miller M, Lishko PV, Cherr GN, Meyers SA, Tollner T. Progesterone Accelerates the Completion of Sperm Capacitation and Activates CatSper Channel in Spermatozoa from the Rhesus Macaque. Biology of reproduction. 2015. doi:10.1095/biolreprod.115.129783
Sumigama, S., et al. "Progesterone Accelerates the Completion of Sperm Capacitation and Activates CatSper Channel in Spermatozoa from the Rhesus Macaque." Biology of reproduction, 2015.