Dysregulation of follicle development in a mouse model of premature ovarian insufficiency

Abstract

Premature ovarian insufficiency (POI) occurs in 1% of reproductive-age women. The ovarian manifestation ranges from the presence of a variable population of follicles (follicular) to the absence of follicles (afollicular), and in the majority of cases the cause is unknown. A transgenic mouse model of follicular POI, the Double Mutant (DM), arises from oocyte-specific deletion of Mgat1 and C1galt1 required for the generation of O- and N-glycans. DM females are subfertile at 6 weeks, infertile by 9 weeks and exhibit POI by 12 weeks of age. In this study we investigate the cause of the reduced fertility at 6 weeks and infertility at 9 weeks of DM females. Ovary sections were used to analyse follicle and corpora lutea (CL) numbers, apoptosis, and levels of laminin and 3β-hydroxysteroid dehydrogenase using immunohistochemistry. After POI, DM females unexpectedly remained sexually receptive. At both 6 and 9 weeks, DM ovaries contained more primary follicles, however, at 9 weeks DM follicles were proportionally healthier, revealed by TUNEL analysis compared with Controls. In 9 week DM ovaries (collected post-mating), secondary follicles had theca and basal lamina structure abnormalities, whilst preovulatory follicles failed to ovulate resulting in the presence of numerous luteinised unruptured follicles, indicative of ovulation failure. Finally, DM ovaries contained more regressing CL with decreased luteal cell apoptosis indicative of a defect in CL regression. Identifying these follicular modifications have provided insight into the aetiology of a model of POI and highlight targets to investigate with the hope of developing new fertility treatments.

Mechanism of resveratrol in improving ovarian function in a rat model of premature ovarian insufficiency

“…Despite changes in mental and active status, vaginal epithelial cytology smears showing a normal estrous cycle (4–5 days and the estrus period, pre‐estrus, estrus and late‐estrus emerged alternately) were used as exclusion criteria for POI. Previous studies have shown that disordered estrous cycles indicate successful establishment of a POI model . The optimum concentration of tripterygium wilfordii polyglycoside tablets used in this study was based on the rat model of induced POI by Hao Juan…”

Ovulation and ovarian wound healing are impaired with advanced reproductive age

“…The first of these phenotypes was oocytes trapped within CLs, or luteinized but unruptured follicles. The presence of an oocyte in a CL indicates that the follicle luteinized before rupture and the oocyte was not ovulated [28] ( Figure 5AI). This could be due to follicles that luteinized prior to rupture or luteinization that occurred because follicles failed to rupture.…”

Essential role of Bone morphogenetic protein 15 in porcine ovarian and follicular development and ovulation

“…This excess expression of LHR suggested premature luteinization in TGF follicles, which was also demonstrated by the dramatically raised expression of 3βHSD (3β-hydroxysteroid dehydrogenase) in TGF SFs (Fig. 5B)(Grasa et al, 2016). In consideration of the striking features of reduced follicle number and degraded GCs in the TGF follicles, we then detected the expression levels of caspase 3 and Ki67 to assess the cell apoptosis and proliferation activity.…”