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Premature ovarian insufficiency (POI) occurs in 1% of women of reproductive age. 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 sub-fertile 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 3B-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 to 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 etiology of a model of POI and highlight targets to investigate with the hope of developing new fertility treatments.

Type

Journal article

Journal

Reproduction (Cambridge, England)

Publication Date

31/08/2016

Addresses

P Grasa, Nuffield Department of Obstetrics & Gynaecology, University of Oxford, Oxford, United Kingdom of Great Britain and Northern Ireland.