Portal de Periódicos da CAPES

CD38 regulates ovarian function and fecundity via NAD+ metabolism

2023; Cell Press; Volume: 26; Issue: 10 Linguagem: Inglês

10.1016/j.isci.2023.107949

2589-0042

Rosalba Perrone, Prasanna Vadhana Ashok Kumaar, Lauren Haky, Cosmo Hahn, Rebeccah Riley, Julia L. Balough, Giuliana Zaza, Bikem Soygur, Kaitlyn Hung, Leandro Prado, Herbert G. Kasler, Ritesh Tiwari, Hiroyuki Matsui, Genesis Vega Hormazabal, Indra Heckenbach, Morten Scheibye‐Knudsen, Francesca E. Duncan, Eric Verdin,

Adenosine and Purinergic Signaling

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, an 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.