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

A single-cell atlas of the aging mouse ovary DOI Creative Commons

José V. V. Isola,

Sarah R. Ocañas,

Chase R. Hubbart

et al.

Nature Aging, Journal Year: 2024, Volume and Issue: 4(1), P. 145 - 162

Published: Jan. 10, 2024

Abstract Ovarian aging leads to diminished fertility, dysregulated endocrine signaling and increased chronic disease burden. These effects begin emerge long before follicular exhaustion. Female humans experience a sharp decline in fertility around 35 years of age, which corresponds declines oocyte quality. Despite growing body work, the field lacks comprehensive cellular map transcriptomic changes mouse ovary identify early drivers ovarian decline. To fill this gap we performed single-cell RNA sequencing on tissue from young (3-month-old) reproductively aged (9-month-old) mice. Our analysis revealed doubling immune cells ovary, with lymphocyte proportions increasing most, was confirmed by flow cytometry. We also found an age-related downregulation collagenase pathways stromal fibroblasts, rises fibrosis. Follicular displayed stress-response, immunogenic fibrotic pathway inductions aging. This report provides critical insights into mechanisms responsible for phenotypes. The data can be explored interactively via Shiny-based web application.

Language: Английский

Citations

60
Cellular atlas of the human ovary using morphologically guided spatial transcriptomics and single-cell sequencing DOI Creative Commons
Andrea Jones, D. Ford Hannum, Jordan H. Machlin

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(14)

Published: April 5, 2024

The reproductive and endocrine functions of the ovary involve spatially defined interactions among specialized cell populations. Despite ovary’s importance in fertility health, functional attributes ovarian cells are largely uncharacterized. Here, we profiled >18,000 genes 257 regions from ovaries two premenopausal donors to examine units ovary. We also generated single-cell RNA sequencing data for 21,198 three additional identified four major types immune subtypes. Custom selection sampling areas revealed distinct gene activities oocytes, theca, granulosa cells. These contributed panels oocyte-, theca-, granulosa-specific genes, thus expanding knowledge molecular programs driving follicle development. Serial samples around oocytes across cortex medulla uncovered previously unappreciated variation hormone extracellular matrix remodeling activities. This combined spatial atlas serves as a resource future studies rare pathological states

Language: Английский

Citations

18
NADase CD38 is a key determinant of ovarian aging DOI Creative Commons
Qingling Yang, Wenhui Chen, Luping Cong

et al.

Nature Aging, Journal Year: 2023, Volume and Issue: 4(1), P. 110 - 128

Published: Dec. 21, 2023

Abstract The ovary ages earlier than most other tissues, yet the underlying mechanisms remain elusive. Here a comprehensive analysis of transcriptomic landscapes in different organs young and middle-aged mice revealed that ovaries showed expression age-associated genes, identifying increased NADase CD38 decreased NAD + levels mice. Bulk single-cell RNA sequencing deletion mitigated ovarian aging, preserving fertility follicle reserve aged by countering age-related gene changes intercellular communication alterations. Mechanistically, onset inflammation induced higher ovary, thereby accelerating aging. Consistently, pharmacological inhibition enhanced Our findings aging relative to organs, providing potential therapeutic target for ameliorating female infertility.

Language: Английский

Citations

33
A spatiotemporal molecular atlas of the ovulating mouse ovary DOI Creative Commons
Madhav Mantri, H. Zhang, E. Spanos

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(5)

Published: Jan. 22, 2024

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 in mice. Our analysis revealed dynamic transitions within granulosa types that occur tight coordination with mesenchymal proliferation. We identified 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 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

16
A multi-omic single-cell landscape of the aging mouse ovary DOI
Jian Zhang,

Shunze Jia,

Zehua Zheng

et al.

GeroScience, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 11, 2025

Language: Английский

Citations

1
CD38 regulates ovarian function and fecundity via NAD+ metabolism DOI Creative Commons
Rosalba Perrone,

Prasanna Vadhana Ashok Kumaar,

Lauren Haky

et al.

iScience, Journal Year: 2023, Volume and Issue: 26(10), P. 107949 - 107949

Published: Sept. 16, 2023

Language: Английский

Citations

22
Bulk and single-cell transcriptome datasets of the mouse fetal and adult rete ovarii and surrounding tissues DOI Creative Commons
Dilara N. Anbarci,

Rebecca O’Rourke,

Yu Xiang

et al.

Scientific Data, Journal Year: 2024, Volume and Issue: 11(1)

Published: April 13, 2024

Abstract The rete ovarii (RO) is an epithelial structure that arises during development in close proximity to the ovary and persists throughout adulthood. However, functional significance of RO remains elusive, it absent from recent discussions female reproductive anatomy. comprises three regions: intraovarian within ovary, extraovarian periovarian tissue, connecting linking two. We hypothesize plays a pivotal role ovarian homeostasis responses physiological changes. To begin uncover nature function cells, we conducted transcriptomic profiling RO. This study presents datasets, reports our analysis quality control approaches for bulk, single-cell, nucleus-level transcriptomics fetal adult tissues using Pax8-rtTA; Tre-H2B-GFP mouse line, where all regions express nuclear GFP. integration rigorous validation these datasets will advance understanding RO’s roles development, maturation, fertility.

Language: Английский

Citations

7
FOXL2 interaction with different binding partners regulates the dynamics of ovarian development DOI Creative Commons
Roberta Migale, Michelle Neumann, Richard Mitter

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(12)

Published: March 22, 2024

The transcription factor FOXL2 is required in ovarian somatic cells for female fertility. Differential timing of

Language: Английский

Citations

6
Durable contraception in the female domestic cat using viral-vectored delivery of a feline anti-Müllerian hormone transgene DOI Creative Commons

Lindsey M. Vansandt,

Marie-Charlotte Meinsohn, Philippe Godin

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: June 6, 2023

Abstract Eighty percent of the estimated 600 million domestic cats in world are free-roaming. These typically experience suboptimal welfare and inflict high levels predation on wildlife. Additionally, euthanasia healthy animals overpopulated shelters raises ethical considerations. While surgical sterilization is mainstay pet population control, there a need for efficient, safe, cost-effective permanent contraception alternatives. Herein, we report evidence that single intramuscular treatment with an adeno-associated viral vector delivering anti-Müllerian hormone transgene produces long-term cat. Treated females followed over two years, during which expression, anti-transgene antibodies, reproductive hormones monitored. Mating behavior success measured mating studies. Here show ectopic expression does not impair sex steroids nor estrous cycling, but prevents breeding-induced ovulation, resulting safe durable female

Language: Английский

Citations

15
Cellular atlases of ovarian microenvironment alterations by diet and genetically-induced obesity DOI
Yonghui Jiang, Xueying Gao, Yue Liu

et al.

Science China Life Sciences, Journal Year: 2023, Volume and Issue: 67(1), P. 51 - 66

Published: Sept. 15, 2023

Language: Английский

Citations

14