CD38 regulates ovarian function and fecundity via NAD+ metabolism

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  • Rosalba Perrone
  • Prasanna Vadhana Ashok Kumaar
  • Lauren Haky
  • Cosmo Hahn
  • Rebeccah Riley
  • Julia Balough
  • Giuliana Zaza
  • Bikem Soygur
  • Kaitlyn Hung
  • Leandro Prado
  • Herbert G. Kasler
  • Ritesh Tiwari
  • Hiroyuki Matsui
  • Genesis Vega Hormazabal
  • Heckenbach, Indra John
  • Scheibye-Knudsen, Morten
  • Francesca E. Duncan
  • Eric Verdin
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.
OriginalsprogEngelsk
Artikelnummer107949
TidsskriftiScience
Vol/bind26
Udgave nummer10
Antal sider27
ISSN2589-0042
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
We thank Dr. Elena Silva, Kaitlyn Vitangcol, Stella Breslin, and Harris Ingle for technical assistance and useful discussion. This study was supported by the Bia-Echo Foundation, the Sergey Brin Family Foundation and the Buck Institute For Research on Aging Institutional fundings. Conceptualization, R.P. P.V.A.K. L.H. F.E.D. E.V.; Methodology, P.V.A.K. L.H. C.H, J.B. B.S.K. K.H.; Formal analysis, R.P. P.V.A.K. L.H. C.H, B.S.K. K.H. H.M. I.H. M.S-K.; Investigation, P.V.A.K. L.H. C.H, R.R. G.Z. B.S.K. K.H. L.P. R.T. G.V.H.; Writing—original draft preparation, R.P. P.V.A.K. L.H. C.H. Writing—review and editing, R.P. P.V.A.K. F.E.D.; Supervision, R.P. F.E.D. E.V.; Funding acquisition, E.V. All authors have read and agreed to the published version of the manuscript. E.V. is a scientific co-founder, shareholder and advisors of Napa Therapeutics, Ltd. E.V. R.P. and P.V.A.K. receive research support from Napa Therapeutics, Ltd. We support inclusive, diverse, and equitable conduct of research.

Funding Information:
We thank Dr. Elena Silva, Kaitlyn Vitangcol, Stella Breslin, and Harris Ingle for technical assistance and useful discussion. This study was supported by the Bia-Echo Foundation , the Sergey Brin Family Foundation and the Buck Institute For Research on Aging Institutional fundings .

Publisher Copyright:
© 2023 The Authors

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