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Macrophage activation drives ovarian failure and masculinization.

ABSTRACT: In humans, premature ovarian insufficiency (POI) is caused by autoimmunity and genetic factors, such as mutation of BMP15, a key ovarian determining gene. The cellular mechanisms associated with ovarian failure caused by BMP15 mutation and immune contributions to the disorder are not understood. BMP15â€™s role in ovarian follicle development is conserved in vertebrates, including zebrafish. Using zebrafish, we established a causal link between macrophage activation and ovarian failure. We identified a germline-somatic gonadal cell-macrophage axis underlying ovarian atresia. Germline loss of Bmp15 triggers this axis that single-cell RNA sequencing and genetic analyses indicate involves activation of ovarian somatic cells that express conserved macrophage-activating ligands. Genetic ablation of macrophages blocks premature oocyte loss. Thus, the axis identified here represents potential therapeutic targets to preserve female fertility.

One-sentence summary

Sex reversal due to Bmp15 deficiency requires macrophage activation by Csf1a, which is expressed by specialized pre-follicle cells in zebrafish.

SUBMITTER: Bravo P

PROVIDER: S-EPMC9881905 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Macrophage activation drives ovarian failure and masculinization.

Bravo Paloma P Liu Yulong Y Draper Bruce W BW Marlow Florence L FL

bioRxiv : the preprint server for biology 20230103

In humans, premature ovarian insufficiency (POI) is caused by autoimmunity and genetic factors, such as mutation of BMP15, a key ovarian determining gene. The cellular mechanisms associated with ovarian failure caused by BMP15 mutation and immune contributions to the disorder are not understood. BMP15's role in ovarian follicle development is conserved in vertebrates, including zebrafish. Using zebrafish, we established a causal link between macrophage activation and ovarian failure. We identifi ...[more]

PMID: 36711702

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Dataset Information

Macrophage activation drives ovarian failure and masculinization.

One-sentence summary

Publications

Macrophage activation drives ovarian failure and masculinization.

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