A Spatiotemporal Molecular Atlas of the Ovulating Mouse Ovary DOI Creative Commons
Madhav Mantri,

Hanxue Hannah Zhang,

E. Spanos

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 22, 2023

Ovulation is essential for reproductive success, yet the underlying cellular and molecular mechanisms are far from clear. Here, we applied high-resolution spatiotemporal transcriptomics to map out cell-type- ovulation-stage-specific programs as function of time during follicle maturation ovulation in mice. Our analysis revealed dynamic transitions within granulosa cell types that occur tight coordination with mesenchymal proliferation. We identified new markers emerging cumulus fate preantral-to-antral transition. describe transcriptional respond rapidly stimulation those associated rupture, highlighting prominent roles apoptotic metabolic pathways final stages maturation. further report stage-specific oocyte-cumulus interactions diverging differentiation follicles approaching ovulation. Collectively, this study provides insights into processes regulate mouse ovarian important implications advancing therapeutic strategies medicine.

Language: Английский

The Continued Absence of Functional Germline Stem Cells in Adult Ovaries DOI Creative Commons
Masahito Yoshihara, Magdalena Wagner, Anastasios Damdimopoulos

et al.

Stem Cells, Journal Year: 2022, Volume and Issue: 41(2), P. 105 - 110

Published: Sept. 25, 2022

Ovaries are central to development, fertility, and reproduction of women. A particularly interesting feature ovaries is their accelerated aging compared other tissues, leading loss function far before organs senesce. The limited pool ovarian follicles generated birth once exhausted, menopause will inevitably commence around the age 50 years marking end fertility. Yet, there reports suggesting presence germline stem cells neo-oogenesis in adult human ovaries. These observations have fueled a long debate, created experimental fertility treatments, opened business opportunities. Our recent analysis cell types cortex women fertile could not find evidence cells. Like before, our work has been met with critique methodological shortcomings. We agree that excellence starts methods welcome discussion on pros cons different protocols. In this commentary, we discuss re-interpretation work.

Language: Английский

Citations

12

Deleterious variants in RNF111 impair female fertility and induce premature ovarian insufficiency in humans and mice DOI
Chengcheng Song, Yingying Qin, Yan Li

et al.

Science China Life Sciences, Journal Year: 2024, Volume and Issue: 67(7), P. 1325 - 1337

Published: June 11, 2024

Language: Английский

Citations

2

Nur77 improves ovarian function in reproductive aging mice by activating mitophagy and inhibiting apoptosis DOI Creative Commons
Ying Yao, Bin Wang,

Kaihua Yu

et al.

Reproductive Biology and Endocrinology, Journal Year: 2024, Volume and Issue: 22(1)

Published: July 23, 2024

Abstract Reproductive aging not only affects the fertility and physical mental health of women but also accelerates process other organs. There is an urgent need newfor novel mechanisms, targets, drugs to break vicious cycle mitochondrial dysfunction, redox imbalance, germ cell apoptosis associated with ovarian aging. Autophagy, recognized as a longevity mechanism, has recently become focal point in anti-aging research. Although mitophagy type autophagy, its role regulatory mechanisms aging, particularly age-related function decline, remain unclear. Nerve growth factor inducible gene B (Nur77) early response that can be stimulated by oxidative stress, DNA damage, metabolism, inflammation. Recent evidence recommends decreased expression Nur77 myocardial fibrosis, renal Parkinson's disease; however, association been studied yet. We herein identified regulator senescence, apoptosis, found overexpression activate mitophagy, improve reduce ultimately enhance reserve aged mice ovaries. Furthermore, we discovered between AKT pathway through String molecular docking analyses. Experimental confirmation revealed AKT/mTOR signaling involved regulation function. In conclusion, our results suggest promising target for preventing treating decline related reproductive

Language: Английский

Citations

2

Transcriptomic signatures of WNT-driven pathways and granulosa cell-oocyte interactions during primordial follicle activation DOI Creative Commons
Hinako M. Takase, Tappei Mishina, Tetsutaro Hayashi

et al.

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(10), P. e0311978 - e0311978

Published: Oct. 23, 2024

Primordial follicle activation (PFA) is a pivotal event in female reproductive biology, coordinating the transition from quiescent to growing follicles. This study employed comprehensive single-cell RNA sequencing gain insights into detailed regulatory mechanisms governing synchronized dormancy and between granulosa cells (GCs) oocytes with progression of PFA process. Wntless ( Wls ) conditional knockout (cKO) mice served as unique model, suppressing pre-GCs GCs, disrupting somatic cell-derived WNT signaling ovary. Our data revealed immediate transcriptomic changes GCs post-PFA cKO mice, leading divergent trajectory, while exhibited modest alterations. Subpopulation analysis identified molecular pathways affected by on GC maturation, along specific gene signatures linked dormant activated oocytes. Despite minimal evidence continuous up-regulation dormancy-related genes oocytes, loss (pre-)GCs impacted expression even before PFA, subsequently influencing them globally. The infertility observed was attributed compromised GC-oocyte crosstalk microenvironment for highlights role WNT-signaling pathway its signature, emphasizing importance intercellular orchestrating folliculogenesis.

Language: Английский

Citations

2

A Spatiotemporal Molecular Atlas of the Ovulating Mouse Ovary DOI Creative Commons
Madhav Mantri,

Hanxue Hannah Zhang,

E. Spanos

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 22, 2023

Ovulation is essential for reproductive success, yet the underlying cellular and molecular mechanisms are far from clear. Here, we applied high-resolution spatiotemporal transcriptomics to map out cell-type- ovulation-stage-specific programs as function of time during follicle maturation ovulation in mice. Our analysis revealed dynamic transitions within granulosa cell types that occur tight coordination with mesenchymal proliferation. We identified new markers emerging cumulus fate preantral-to-antral transition. describe transcriptional respond rapidly stimulation those associated rupture, highlighting prominent roles apoptotic metabolic pathways final stages maturation. further report stage-specific oocyte-cumulus interactions diverging differentiation follicles approaching ovulation. Collectively, this study provides insights into processes regulate mouse ovarian important implications advancing therapeutic strategies medicine.

Language: Английский

Citations

6