Rescue of follicle development after oocyte-induced ovary dysfunction and infertility in a model of POI
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-specifi...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2023.1202411/full |
| _version_ | 1827874076986703872 |
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| author | Sairah Sheikh Belinda K. M. Lo Heidy Kaune Jassimran Bansal Anna Deleva Suzannah A. Williams |
| author_facet | Sairah Sheikh Belinda K. M. Lo Heidy Kaune Jassimran Bansal Anna Deleva Suzannah A. Williams |
| author_sort | Sairah Sheikh |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T16:46:07Z |
| format | Article |
| id | doaj.art-ff7701fc5fd648f78e1476ba73dcb62b |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-03-12T16:46:07Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-ff7701fc5fd648f78e1476ba73dcb62b2023-08-08T12:25:45ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-08-011110.3389/fcell.2023.12024111202411Rescue of follicle development after oocyte-induced ovary dysfunction and infertility in a model of POISairah SheikhBelinda K. M. LoHeidy KauneJassimran BansalAnna DelevaSuzannah A. WilliamsThe 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.https://www.frontiersin.org/articles/10.3389/fcell.2023.1202411/fulloocytefollicle developmentprimary folliclegranulosa cellsprimary ovarian insufficiencypremature ovarian failure |
| spellingShingle | Sairah Sheikh Belinda K. M. Lo Heidy Kaune Jassimran Bansal Anna Deleva Suzannah A. Williams Rescue of follicle development after oocyte-induced ovary dysfunction and infertility in a model of POI Frontiers in Cell and Developmental Biology oocyte follicle development primary follicle granulosa cells primary ovarian insufficiency premature ovarian failure |
| title | Rescue of follicle development after oocyte-induced ovary dysfunction and infertility in a model of POI |
| title_full | Rescue of follicle development after oocyte-induced ovary dysfunction and infertility in a model of POI |
| title_fullStr | Rescue of follicle development after oocyte-induced ovary dysfunction and infertility in a model of POI |
| title_full_unstemmed | Rescue of follicle development after oocyte-induced ovary dysfunction and infertility in a model of POI |
| title_short | Rescue of follicle development after oocyte-induced ovary dysfunction and infertility in a model of POI |
| title_sort | rescue of follicle development after oocyte induced ovary dysfunction and infertility in a model of poi |
| topic | oocyte follicle development primary follicle granulosa cells primary ovarian insufficiency premature ovarian failure |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2023.1202411/full |
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