Endometriosis is an estrogen-dependent condition that affects 5 million American women; however, its etiology is not fully understood. The development of the baboon model of endometriosis provides an extremely powerful tool to investigate the development and progression of endometriosis from the early invasive phase to the advanced established disease. The inflammatory reaction that occurs in the peritoneal cavity at the site of endometriotic lesions does not clear the refluxed endometrial fragments. Moreover, this reaction appears to promote the survival of the tissue and the development of the disease. Exploration of the interactions between peritoneal macrophages and cytotoxic T cells and endometrial cells will determine whether their ability to scavenge and induce apoptosis is altered. Determining the mechanism(s) that induces the expression of estrogen and its receptor (ERbeta) is crucial to our understanding of the progression of the disease. The effects of ERbeta activation in endometriotic lesions should be investigated. It is important to determine the effects of estrogen on the function of the immune cells, either directly or indirectly. Finally, determining the effect of events at sites of ectopic endometrium on the eutopic endometrium may elucidate the mechanism(s) of infertility associated with endometriosis.
PMID 12917794 12917794 DOI 10.1055/s-2003-41331 10.1055/s-2003-41331
Cite this article
Hastings, J. M., & Fazleabas, A. T. (2003). Future directions in endometriosis research. Seminars in reproductive medicine, 21(2), 255-262. https://doi.org/10.1055/s-2003-41331
Hastings, Julie M., and Asgerally T. Fazleabas. "Future directions in endometriosis research." Seminars in reproductive medicine, vol. 21, no. 2, 2003, pp. 255-262.
The role of natural killer (NK) cells in the decreased cellular immunity of women with endometriosis was investigated. DESIGN, SETTING, Thirty-four women were investigated prospectively before a CO2-laser laparoscopy for infertility and/or pain at the University Hospital Gasthuisberg. Endometriosis was scored blindly. The cytotoxicity, directed against the endometrium, was mediated by NK cells because this cytotoxicity could be removed by treating the effector cells with the NK-specific anti-Leu-11b monoclonal antibody. Consequently, we evaluated prospectively in those women the lymphocyte-mediated cytotoxicity toward NK sensitive (K562-assay) and autologous endometrial target cells. The NK activity (K562-assay) and the cytotoxicity against autologous endometrial cells were similarly decreased in women with endometriosis and correlated with the severity of the disease. Using heterologous effector cells, the decreased chromium release in women with endometriosis was less pronounced but still present. The decreased cytotoxicity to endometrial cells in women with endometriosis is mainly because of a defect in NK activity but is also partially because of a resistance of the endometrium to NK cytotoxicity.
EndometriosisImmune DysfunctionCellular Immunity DeficiencyAutoimmune Response in Endometriosis
Cell-mediated autoimmune responses were studied by means of in vivo and in vitro techniques in five rhesus monkeys with spontaneous endometriosis. The results were compared with similar data obtained from five normal rhesus monkeys without endometriosis. The in vivo studies included intrademal injection of autologous antigens prepared from uterine endometrium, ectopic endometrium, or peritoneum, or injection of the mitogen, phytohemagglutinin (PHA). Skin biopsies were obtained at 48 hours and evaluated under the light microscope for perivascular lymphocytic infiltration. The mean number of lymphocytes per high-power field after injection of the autologous endometrial antigen was significantly smaller in animals affected by endometriosis than in the control group. There was no significant difference in lymphocytic response to autologous peritoneal antigens between the groups. Animals of both groups responded readily to PHA with marked perivascular lymphocytic infiltration. Lymphocyte stimulation responses to the same autologous antigens or to PHA were evaluated by means of in vitro assays and micro-methods. Lymphocyte stimulation response to autologous endometrial antigens in the group with endometriosis was significantly less than in the control group. There was no significant difference in response to the peritoneal antigens between the groups, and the response to PHA was marked in all animals of both groups. The results of this study indicate that rhesus monkeys with spontaneous endometriosis have an altered cellular immune response to autologous antigens. Although the animals were immunologically competent, as judged by responses to PHA, both in vivo and in vitro studies indicated a decrease in the cell-mediated immune response to autologous endometrial antigens. These data suggest that endometrial cells translocated from their normal location may implant only in women with specific alteration in cell-mediated immunity. New light is thus shed on the cause of endometriosis.
InfertilityContaminant Exposure and FertilityBPA Phthalate Pesticide EffectsSemen Quality and Chemical Exposure
This review article summarizes the epidemiological findings published between 2011 and 2016 concerning bisphenol A (BPA), phthalates, dioxins, pesticides, air pollution, fracking chemicals, triclosan, and parabens and fertility parameters in men (i.e., semen volume, sperm concentration, sperm motility, and sperm morphology) as well as fertility parameters in women (i.e., cyclicity, fertility treatment outcomes), pregnancy outcomes (i.e., preterm birth,miscarriage), and reproductive disorders (i.e., polycystic ovary syndrome, endometriosis, and uterine fibroids). Overall, this review indicates that several environmental toxicants are significantly associated with reduced fertility parameters in men and women as well as several reproductive disorders in women. Although many studies reported that the selected exposures are associated with adverse fertility outcomes, several studies reported null associations. Thus, future studies are still needed to better elucidate the associations and potential mechanisms between these environmental chemicals and fertility outcomes in men and women.
Novak C et al., 2013·Seminars in Reproductive Medicine
Health disparities are observed in all fields of medicine and reproductive health is not immune to this phenomenon. The incidence of women using infertility treatments to conceive is increasing. Women undergoing assisted reproduction appear to be at increased risk of adverse outcomes, and minority women tend to be at even greater risk. This article examines several adverse obstetrical outcomes including preterm birth, congenital malformations, and preeclampsia among women receiving infertility treatments compared with those who conceive spontaneously. It will further examine societal costs associated with these procedures.