PUBLICATION
Macrophage activation drives ovarian failure and masculinization in zebrafish
- Authors
- Bravo, P., Liu, Y., Draper, B.W., Marlow, F.L.
- ID
- ZDB-PUB-231123-4
- Date
- 2023
- Source
- Science advances 9: eadg7488eadg7488 (Journal)
- Registered Authors
- Draper, Bruce, Liu, Yulong, Marlow, Florence
- Keywords
- none
- MeSH Terms
-
- Animals
- Female
- Humans
- Macrophage Activation/genetics
- Male
- Oocytes/physiology
- Primary Ovarian Insufficiency*/genetics
- Zebrafish*
- PubMed
- 37992158 Full text @ Sci Adv
Citation
Bravo, P., Liu, Y., Draper, B.W., Marlow, F.L. (2023) Macrophage activation drives ovarian failure and masculinization in zebrafish. Science advances. 9:eadg7488eadg7488.
Abstract
BMP15 is a conserved regulator of ovarian development and maintenance in vertebrates. In humans, premature ovarian insufficiency is caused by autoimmunity and genetic factors, including mutation of BMP15. The cellular mechanisms underlying ovarian failure caused by BMP15 mutation and immune contributions are not understood. Using zebrafish, we established a causal link between macrophage activation and ovarian failure, which, in zebrafish, causes sex reversal. We define a germline-soma signaling axis that activates macrophages and drives ovarian failure and female-to-male sex reversal. Germline loss of zebrafish Bmp15 impairs oogenesis and initiates this cascade. Single-cell RNA sequencing and genetic analyses implicate ovarian somatic cells that express conserved macrophage-activating ligands as mediators of ovarian failure and sex reversal. Genetic ablation of macrophages or elimination of Csf1Rb ligands, Il34 or Csf1a, delays or blocks premature oocyte loss and sex reversal. The axis identified here provides insight into the cells and pathways governing oocyte and ovary maintenance and potential therapeutic targets to preserve female fertility.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping