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CD38 regulates ovarian function and fecundity via NAD + metabolism

CD38 regulates ovarian function and fecundity via NAD + metabolism

来源:bioRxiv_logobioRxiv
英文摘要

Summary Mammalian female reproductive lifespan is typically significantly shorter than life expectancy and is associated with a decrease in ovarian NAD+ levels. However, the mechanisms underlying this loss of ovarian NAD+ are unclear. Here, we show that CD38, a NAD+ consuming enzyme, is expressed in the ovarian extrafollicular space, primarily in immune cells, and its levels increase with reproductive age. Reproductively young mice lacking CD38 exhibit larger primordial follicle pools, elevated ovarian NAD+ levels, and increased fecundity relative to wild type controls. This larger ovarian reserve results from a prolonged window of follicle formation during early development. However, the beneficial effect of CD38 loss on reproductive function is not maintained at advanced age. Our results demonstrate a novel role of CD38 in regulating ovarian NAD+ metabolism and establishing the ovarian reserve, a critical process that dictates a female’s reproductive lifespan.

Ashok Kumaar Prasanna Vadhana、Zaza Giuliana、Haky Lauren、Hahn Cosmo、Tiwari Ritesh、Verdin Eric、Kasler Herbert G.、Duncan Francesca Elizabeth、Soygur Bikem、Hung Kaitlyn、Hormazabal Genesis Vega、Balough Julia、Prado Leandro、Riley Rebeccah、Matsui Hiroyuki、Perrone Rosalba

Buck Institute For Research on AgingBuck Institute For Research on AgingBuck Institute For Research on Aging||The Dominican University of CaliforniaBuck Institute For Research on AgingBuck Institute For Research on AgingBuck Institute For Research on AgingBuck Institute For Research on AgingBuck Institute For Research on Aging||Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern UniversityBuck Institute For Research on AgingBuck Institute For Research on AgingBuck Institute For Research on AgingBuck Institute For Research on AgingBuck Institute For Research on AgingBuck Institute For Research on AgingBuck Institute For Research on AgingBuck Institute For Research on Aging

10.1101/2023.05.08.539779

基础医学生理学生物化学

Female reproductive agingNAD+ MetabolismCD38Fertility

Ashok Kumaar Prasanna Vadhana,Zaza Giuliana,Haky Lauren,Hahn Cosmo,Tiwari Ritesh,Verdin Eric,Kasler Herbert G.,Duncan Francesca Elizabeth,Soygur Bikem,Hung Kaitlyn,Hormazabal Genesis Vega,Balough Julia,Prado Leandro,Riley Rebeccah,Matsui Hiroyuki,Perrone Rosalba.CD38 regulates ovarian function and fecundity via NAD + metabolism[EB/OL].(2025-03-28)[2025-05-01].https://www.biorxiv.org/content/10.1101/2023.05.08.539779.点此复制

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