Rescue of follicle development after oocyte-induced ovary dysfunction and infertility in a model of POI

Journal article

The mechanisms and aetiology underlying the development of premature ovarian insufficiency (POI) are poorly understood. However, the oocyte clearly has a role as demonstrated by the Double Mutant (DM) mouse model where ovarian dysfunction (6 weeks) is followed by POI (3 months) due to oocyte-specific deletion of complex and hybrid N- and O-glycans. The ovaries of DM mice contain more primary follicles (3a stage) accompanied by fewer developing follicles, indicating a block in follicle development. To investigate this block, we first analysed early follicle development in postnatal (8-day), pre-pubertal (3-week) and post-pubertal (6-week and 3-month) DM (C1galt1F/FMgat1F/F:ZP3Cre) and Control (C1galt1F/FMgat1F/F) mice. Second, we investigated if transplantation of DM ovaries into a “normal” endocrine environment would restore follicle development. Third, we determined if replacing DM ovarian somatic cells would rescue development of DM oocytes. At 3-week, DM primary 3a follicles contain large oocytes accompanied by early development of a second GC layer and increased GC proliferation. At 6-week, DM primary 3a follicles contain abnormally large oocytes, accompanied with decreased GC proliferation. Transplantation of DM ovaries into a ‘normal’ endocrine environment did not restore normal follicle development. However, replacing somatic cells by generating reaggregated ovaries (ROs) did enable follicle development to progress and thus highlighted intra-ovarian factors were responsible for the onset of POI in DM females. Thus, these studies demonstrate oocyte-initiated altered communication between GCs and oocytes results in abnormal primary follicles which fail to progress and leads to POI.

Authors: Sheikh, S; Lo, BKM; Kaune, H; Bansal, J; Deleva, A

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Frontiers Media
• Journal: Frontiers in Cell and Developmental Biology
• Volume: 11
• Pages: 1202411-1202411
• Article number: 1202411
• Publication date: 2023-08-08
• DOI: 10.3389/fcell.2023.1202411
• EISSN: 2296-634X
• ISSN: 2296-634X
• Language: English
• Keywords: Andrology; Ovarian reserve; Gynecology; Genetics; Oocyte; Biology; Infertility; Ovary; Internal medicine; Female infertility; Ovarian follicle; Follicle; Medicine; Pregnancy; Cell biology; Embryo