Analyzing the cellular and molecular atlas of ovarian mesenchymal cells provides a strategy against female reproductive aging

Jia, Longzhong; Liang, Jing; Niu, Shudong; Wang, Yibo; Yang, Jinqiang; Li, Lingyu; Wang, Ge; Xu, Xueqiang; Mu, Lu; Cheng, Kaixin; Yang, Xuebing; Wang, Yijing; Luo, Hanpeng; Xia, Guoliang; Ke, Youqi; Zhang, Yan; Zhang, Hua

doi:10.1007/s11427-022-2335-6

Cited by 5 publications

(1 citation statement)

References 84 publications

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“…The application of emerging single-cell sequencing technologies has advanced our understanding of transcriptional profiles of various tissues and organs at diverse physiological and pathological conditions and at a high resolution and high accuracy ( Cheng et al, 2021 ; He et al, 2020a , 2020b ; Huang et al, 2022 ; Jing et al, 2023 ; Lehallier et al, 2019 ; Leng and Pawelec, 2022 ; Ma et al, 2023 ; Sun et al, 2023 ; Tang et al, 2009 ; Zhou et al, 2022 ). Taking advantage of single-cell transcriptomics, pioneering studies have revealed the cell compositions, and cell type-specific transcriptional features of ovarian development and aging in both rodents and primates ( Isola et al, 2023 ; Jia et al, 2023 ; Lengyel et al, 2022 ; Wagner et al, 2020 ; Wang et al, 2020 ). However, due to high cell heterogeneity of the ovary and its intricate geographical distribution ( Fan and Chuva de Sousa Lopes, 2021 ), progress toward understanding the cellular and molecular programs underlying ovarian degeneration from a spatial perspective, and particularly in primates, has remained limited.…”

Section: Introductionmentioning

confidence: 99%

Aging hallmarks of the primate ovary revealed by spatiotemporal transcriptomics

Lu,

Jing,

Zhang

et al. 2023

Protein &Amp; Cell

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The ovary is indispensable for female reproduction, and its age-dependent functional decline is the primary cause of infertility. However, the molecular basis of ovarian aging in higher vertebrates remains poorly understood. Herein, we apply spatiotemporal transcriptomics to benchmark architecture organization as well as cellular and molecular determinants in young primate ovaries and compare these to aged primate ovaries. From a global view, somatic cells within the non-follicle region undergo more pronounced transcriptional fluctuation relative to those in the follicle region, likely constituting a hostile microenvironment that facilitates ovarian aging. Further, we uncovered that inflammation, the senescent associated secretory phenotype (SASP), senescence and fibrosis are the likely primary contributors to ovarian aging (PCOA). Of note, we identified spatial co-localization between a PCOA-featured spot and an unappreciated MT2 (Metallothionein 2) highly expressing spot (MT2high) characterized by high levels of inflammation, potentially serving as an aging hotspot in the primate ovary. Moreover, with advanced age, a subpopulation of MT2high accumulates, likely disseminating and amplifying the senescent signal outward. Our study establishes the first primate spatiotemporal transcriptomic atlas, advancing our understanding of mechanistic determinants underpinning primate ovarian aging and unraveling potential biomarkers and therapeutic targets for aging and age-associated human ovarian disorders.

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Section: Introductionmentioning

confidence: 99%

Aging hallmarks of the primate ovary revealed by spatiotemporal transcriptomics

Lu,

Jing,

Zhang

et al. 2023

Protein &Amp; Cell

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Deleterious variants in RNF111 impair female fertility and induce premature ovarian insufficiency in humans and mice

Song,

Qin,

et al. 2024

Sci. China Life Sci.

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Single‐cell sequencing reveals the transcriptional alternations of 17β‐estradiol suppressing primordial follicle formation in neonatal mouse ovaries

Yan,

Zhang,

et al. 2024

Cell Proliferation

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Estrogen has been implicated in multiple biological processes, but the variation underlying estrogen‐mediated primordial follicle (PF) formation remains unclear. Here, we show that 17β‐estradiol (E2) treatment of neonatal mice led to the inhibition of PF formation and cell proliferation. Single‐cell RNA sequencing (scRNA‐seq) revealed that E2 treatment caused significant changes in the transcriptome of oocytes and somatic cells. E2 treatment disrupted the synchronised development of oocytes, pre‐granulosa (PG) cells and stromal cells. Mechanistically, E2 treatment disrupted several signalling pathways critical to PF formation, especially down‐regulating the Kitl and Smad1/3/4/5/7 expression, reducing the frequency and number of cell communication. In addition, E2 treatment influenced key gene expression, mitochondrial function of oocytes, the recruitment and maintenance of PG cells, the cell proliferation of somatic cells, as well as disordered the ovarian microenvironment. This study not only revealed insights into the regulatory role of estrogen during PF formation, but also filled in knowledge of dramatic changes in perinatal hormones, which are critical for the physiological significance of understanding hormone changes and reproductive protection.

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Analyzing the cellular and molecular atlas of ovarian mesenchymal cells provides a strategy against female reproductive aging

Cited by 5 publications

References 84 publications

Aging hallmarks of the primate ovary revealed by spatiotemporal transcriptomics

Aging hallmarks of the primate ovary revealed by spatiotemporal transcriptomics

Deleterious variants in RNF111 impair female fertility and induce premature ovarian insufficiency in humans and mice

Single‐cell sequencing reveals the transcriptional alternations of 17β‐estradiol suppressing primordial follicle formation in neonatal mouse ovaries

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