P-329 Endometrioma impairs oocyte development by extensive premature activation of primordial follicles in an experimental endometrioma mouse model

Abstract

Abstract Study question What are the pathological mechanisms of endometrioma-associated poor ovarian function? Summary answer Endometrioma prematurely activated primordial follicles and subsequently impaired ovarian functions through disrupting folliculogenesis and deteriorating oocyte quality. What is known already Endometrioma is the most common subtype of endometriosis, of which the endometriotic lesions implant in the ovary. Women with endometrioma are usually coupled with disrupted folliculogenesis, hampered ovulation, impaired oocyte quality and undesired infertility, presenting with reduced ovarian reserve, low oocyte retrieval rates and poor fertility outcomes. However the underlying mechanisms of the disrupted folliculogenesis, hampered ovulation and impaired oocyte quality in endometrioma-associated infertility are still unclear. Study design, size, duration An experimental mouse model of endometrioma (OMA) was established to study the effects of endometriosis in ovary on the development and functions of follicles. Four to eight mice were included in experimental and sham control groups each. Ovaries were collected 4 weeks after transplantation of endometrial fragments. Follicle counts and specific developmental markers were used to evaluate the development and functions of follicles. Oocyte quality was studied by meiotic competence, cortical distributions and ATP synthesis. Participants/materials, setting, methods Minced endometrial tissues from donor mice were inserted into ovarian bursa in recipient mice. Ovarian follicles in different stages were examined and counted manually with Periodic acid-Schiff staining. Protein expressions of FOXO3, AMH and FSHR were detected by immunohistochemistry to characterise the developing primordial, primary/secondary and antral follicles, respectively. Oocytes were collected from oviduct after superovulation and stained with a-tubulin, LCA-FITC to assess maturity. Main results and the role of chance Successful establishment of endometriotic lesions in ovarian tissues was confirmed morphologically and histologically with a success rate of 83.33% in recipient mice. In the OMA ovaries, absolute counts of the follicles in each developmental stage showed significant reduction when compared with sham controls. Percentage of primordial follicles was significantly reduced, but percentage of advanced-staged follicles was significantly increased. Expression of FOXO3 in primordial follicles, AMH in developing follicles (primary, secondary) and FSHR in antral follicles were all significantly decreased in OMA group. Oocytes isolated from OMA ovaries had lower number and size than controls. Large proportion of the oocytes had significantly higher abnormal spindle rates, indicating mitotic disruption. Moreover, a large proportion of the oocytes also had impaired cortical granule migration, indicating affected organelle organization. Limitations, reasons for caution Studies based on this animal model may not reflect the exact situation in human. Moreover, success rate of the OMA model cannot reach 100%. Other factors contributing to the endometrioma-associated infertility still undetermined in the OMA models. Wider implications of the findings The results demonstrated that endometrioma remarkably deteriorated follicular development, and subsequently impaired oocyte quality by premature activation primordial follicles. The underlying deteriorating effects and mechanism might help to develop novel therapeutic targets to improve fertility outcomes in women with endometrioma. Trial registration number N/A