Epigenetic programming in the ovarian reserve

Hu, Mei‐Chen; Schultz, Richard M.; Namekawa, Satoshi H.

doi:10.1002/bies.202300069

Cited by 3 publications

References 59 publications

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In vitro gametogenesis: Towards competent oocytes

Aizawa,

Peters,

Wutz

2024

BioEssays

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Production of oocytes from pluripotent cell cultures in a dish represents a new paradigm in stem cell and developmental biology and has implications for how we think about life. The spark of life for the next generation occurs at fertilization when sperm and oocyte fuse. In animals, gametes are the only cells that transmit their genomes to the next generation. Oocytes contain in addition a large cytoplasm with factors that direct embryonic development. Reconstitution of mouse oocyte and embryonic development in culture provides experimental opportunities and facilitates an unprecedented understanding of molecular mechanisms. However, the application of in vitro gametogenesis to reproductive medicine or infertility treatment remains challenging. One significant concern is the quality of in vitro‐derived oocytes. Here, we review the current understanding and identify limitations in generating oocytes in vitro. From this basis, we explore opportunities for future improvements of the in vitro approach to generating high‐quality oocytes.

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In vitro gametogenesis: Towards competent oocytes

Aizawa,

Peters,

Wutz

2024

BioEssays

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Epigenetic priming in the male germline

Kitamura,

Namekawa

2024

Current Opinion in Genetics & Development

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Chromatin remodeler CHD4 establishes chromatin states required for ovarian reserve formation, maintenance, and germ cell survival

Munakata,

Hu,

Kitamura

et al. 2024

Preprint

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The ovarian reserve defines female reproductive lifespan, which in humans spans decades due to the maintenance of meiotic arrest in non-growing oocytes (NGO) residing in primordial follicles. Unknown is how the chromatin state of NGOs is established to enable long-term maintenance of the ovarian reserve. Here, we show that a chromatin remodeler, CHD4, a member of the Nucleosome Remodeling and Deacetylase (NuRD) complex, establishes chromatin states required for formation and maintenance of the ovarian reserve. Conditional loss of CHD4 in perinatal mouse oocytes results in acute death of NGOs and depletion of the ovarian reserve. CHD4 establishes closed chromatin at regulatory elements of pro-apoptotic genes to prevent cell death and at specific genes required for meiotic prophase I to facilitate the transition from meiotic prophase I oocytes to meiotic arrested NGOs. In addition, CHD4 establishes closed chromatin at the regulatory elements of pro-apoptotic genes in male germ cells, allowing male germ cell survival. These results demonstrate a role for CHD4 in defining a chromatin state that ensures germ cell survival, thereby enabling the long-term maintenance of both female and male germ cells.

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Epigenetic programming in the ovarian reserve

Cited by 3 publications

References 59 publications

In vitro gametogenesis: Towards competent oocytes

In vitro gametogenesis: Towards competent oocytes

Epigenetic priming in the male germline

Chromatin remodeler CHD4 establishes chromatin states required for ovarian reserve formation, maintenance, and germ cell survival

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