Peritoneal endometriosis impairs ovarian reserve and function in a rat model

ANALÍA RICCI; ROSA INÉS BARAÑAO; BÁRBARA MC CORMACK; DANIELA MADANES; TATIANA BENGOCHEA; FRIDA SCHEFFER; MARIELA ANDREA BILOTAS; MARIANNE BIZZOZZERO; CARLA OLIVARES

Simposio; Frontiers in Reproduction 21th Annual Symposium.; 2018

Introduction:Endometriosis is a chronic gynecological disorder associated with pelvic painand infertility. It is characterized by the presence of endometrial glands andstroma outside the uterine cavity and is estimated to occur in up to 10% ofwomen of reproductive age. Different mechanisms have been proposed to explainendometriosis associated infertility including alterations in follicular andperitoneal environment, in folliculogenesis and in granulosa cells function. Alsoseveral studies have shown a decrease in ovarian reserve associated with the presenceof ovarian endometriomas although other works state that the reduction in ovarianreserve in endometriosis patients is due to the surgery performed to remove theendometriomas. Nevertheless little it?s known about the effect of peritonealendometriosis on ovarian reserve.  Objective:The objective of the present work was to evaluate the effect of peritoneal endometriosison ovarian reserve, ovulation and steroidogenesis in the ovary of rats withexperimentally induced endometriosis. Design:Endometriosis was surgically induced in Sprague Dawley two-month-old female ratsby autotransplantation of uterine horn pieces to the bowel mesothelium. Shamanimals were used as controls. Rats were sacrificed 45 days after surgery atdifferent stages of menstrual cycle (proestrus, estrous and diestrus).  One ovary was fixed and the other one wasused for protein extraction. Lesions were removed in order to histologicallyconfirm endometriosis.Materialsand Methods: Early follicles were counted in ovary sections stainedwith hematoxylin-eosin. AMH KL y GDF-9 expression was assessed in ovaries bywester blot. Estradiol and progesterone serum levels were evaluated by RIA. AromataseP450, P450scc, 3β-HSD, StAR, LHR and COX-2 expression was determined by westernblot in isolated follicles and corpora lutea (CL). PGF-2α was evaluated inserum by ELISA. Ovulated oocytes were counted in the ampulla in the morning ofestrous.    Results: Allanimals presented normal cycles. There were no differences in number of cyclesevaluated and the time of each cycle stage between sham and endometriosisgroups. Females with endometriosis showed a reduced number of primordial,primary and preantral follicles (p<0.05). Accordingly with these results,AMH protein levels were decreased in endometriosis rat ovaries(p<0.05) however KL expression was diminished (p<0.05).   Inaddition, the number of ovulated oocytes was diminished in rats withendometriosis compared to the sham ones (p<0.05). Serum levels of estradiolwere decreased (p<0.01) and progesterone serum levels were increased(p<0.01) in rats with endometriosis. StAR expression decreased in folliclesfrom rats with endometriosis (p<0.001) and increased in CL during estrus(p<0.05). P450scc expression decreased in follicles during proestrus(p<0.05) and increased in CL during estrus (p<0.001) in rats withendometriosis. 3β-HSD expression diminished in CL from rats with endometriosisduring proestrus (p<0.05). Aromatase P450 expression decreased in CL(p<0.001) and follicles (p<0.01) in diestrus and increased in CL duringestrus (p<0.01) in rats with endometriosis. LHR exrpression diminished infollicles (p<0.05) and CL (p<0.01) from rats with endometriosis inproestrus and increased in follicles from endometriosis rats in diestrus (p<0.05).COX-2 expression decreased in CL from endometriosis rats (p<0.05) and infollicles only in proestrus (p<0.05). No significant differences wereobserved in serum levels of PGF-2α between endometriosis andsham animals.  Conclusion:Our results suggest that 45 days of peritoneal endometriosis induction issufficient to diminish ovarian reserve in a rat model.  In addition experimental endometriosis in rats alters steroidogenic proteinsexpression in ovary leading to endocrine and ovulatory changes.