Chromatin remodeler CHD4 establishes chromatin states required for ovarian reserve formation, maintenance, and germ cell survival DOI Creative Commons
Yasuhisa Munakata, Mengwen Hu, Yuka Kitamura

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 13, 2024

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

Language: Английский

Epigenetic priming in the male germline DOI Creative Commons
Yuka Kitamura, Satoshi H. Namekawa

Current Opinion in Genetics & Development, Journal Year: 2024, Volume and Issue: 86, P. 102190 - 102190

Published: April 11, 2024

Language: Английский

Citations

4
Transcriptional Integration of Meiotic Prophase I Progression and Early Oocyte Differentiation DOI Creative Commons
Kimberly M. Abt,

Myles A. Bartholomew,

Alan J. Nixon

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 6, 2025

Female reproductive senescence results from the regulated depletion of a finite pool oocytes called ovarian reserve. This is initially established during fetal development, but that comprise it must remain quiescent for decades until they are activated maturation in adulthood. In order developmentally competent to populate reserve successfully initiate both meiosis and oogenesis. As factors regulate timing fidelity these early events elusive, we assessed precise function transcriptional regulator TAF4b meiotic prophase I progression mouse oocytes. Compared matched controls, E14.5 Taf4b -deficient enter timely manner however, their subsequent through pachytene-to-diplotene transition compromised. Moreover, this disruption associated with reduced ability repair double-strand DNA breaks. Transcriptional profiling reveals between E16.5 E18.5 fail coordinate reduction gene expression induction oocyte differentiation genes. These studies reveal promotes formation part by orchestrating arrest differentiation, which often perceived as separate events.

Language: Английский

Citations

0
Chromatin remodeler CHD4 establishes chromatin states required for ovarian reserve formation, maintenance and male germ cell survival DOI Creative Commons
Yasuhisa Munakata, Mengwen Hu, Yuka Kitamura

et al.

Nucleic Acids Research, Journal Year: 2025, Volume and Issue: 53(3)

Published: Jan. 24, 2025

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

Language: Английский

Citations

0
Clinical efficacy and pharmacological mechanism of Er Zhi Tian Gui formula in enhancing IVF-ET outcomes for diminished ovarian reserve DOI Creative Commons
Wen Chen, Fang Lian, Jing‐Yan Song

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 21, 2025

Objective To investigate the efficacy of Er Zhi Tian Gui Formula (EZTGF) in diminished ovarian reserve (DOR) patients undergoing vitro fertilization-embryo transfer (IVF-ET); to examine pharmacological mechanism EZTGF inhibiting granulosa cell (OGC) apoptosis. Methods A total 120 DOR IVF-ET Affiliated Hospital Shandong University TCM from March December 2021 were randomly assigned (n = 60) or Placebo groups. All participants followed a gonadotropin-releasing hormone antagonist protocol for controlled stimulation, with interventions starting on days 2–3 preceding menstrual cycle and continuing until trigger day. outcomes measured included number oocytes retrieved, embryo quality, pregnancy rates. NEAT1, miR-10b-3p, FOXO3a OGCs expression was analyzed via qRT-PCR. Mechanistic studies conducted using KGN cells, dual-luciferase reporter assays confirming regulatory relationship between FOXO3a. Results 116 completed trial (58 each group). The group showed significant increase both (especially at cleavage stage) rate high-quality embryos, compared (P < 0.05). No statistically differences observed > Cellular experiments that miR-10b-3p inhibits proliferation promotes apoptosis oocyte cells (OGCs). Dual luciferase gene assay confirms target-regulatory NEAT1 treatment partially reversed low FOXO3a, high patients. Conclusion Treatment enhances quality women IVF-ET, which can be attributed modulation NEAT1/miR-10b-3p/FOXO3a pathway. Trial registration: ChiCTR2100052522.

Language: Английский

Citations

0
In vitro gametogenesis: Towards competent oocytes DOI Creative Commons
Eishi Aizawa, Antoine H.F.M. Peters, Anton Wutz

et al.

BioEssays, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 5, 2024

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

Language: Английский

Citations

0
Chromatin remodeler CHD4 establishes chromatin states required for ovarian reserve formation, maintenance, and germ cell survival DOI Creative Commons
Yasuhisa Munakata, Mengwen Hu, Yuka Kitamura

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 13, 2024

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

Language: Английский

Citations

0