CD38 regulates ovarian function and fecundity via NAD+ metabolism

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; Indra Heckenbach; Morten Scheibye-Knudsen; Francesca E. Duncan; Eric Verdin

doi:10.1016/j.isci.2023.107949

CD38 regulates ovarian function and fecundity via NAD⁺ metabolism

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, Indra Heckenbach, Morten Scheibye-Knudsen, Francesca E. Duncan^*, Eric Verdin

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › peer-review

14 Citations (Scopus)

27 Downloads (Pure)

Abstract

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.

Original language	English
Article number	107949
Journal	iScience
Volume	26
Issue number	10
Number of pages	27
ISSN	2589-0042
DOIs	https://doi.org/10.1016/j.isci.2023.107949
Publication status	Published - 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors

Keywords

Biochemistry
Biological sciences
Physiology

Access to Document

10.1016/j.isci.2023.107949Licence: CC BY-NC-ND

FulltextFinal published version, 8.4 MBLicence: CC BY-NC-ND

Cite this

Perrone, R., Ashok Kumaar, P. V., Haky, L., Hahn, C., Riley, R., Balough, J., Zaza, G., Soygur, B., Hung, K., Prado, L., Kasler, H. G., Tiwari, R., Matsui, H., Hormazabal, G. V., Heckenbach, I., Scheibye-Knudsen, M., Duncan, F. E., & Verdin, E. (2023). CD38 regulates ovarian function and fecundity via NAD⁺ metabolism. iScience, 26(10), [107949]. https://doi.org/10.1016/j.isci.2023.107949

CD38 regulates ovarian function and fecundity via NAD⁺ metabolism. / Perrone, Rosalba; Ashok Kumaar, Prasanna Vadhana; Haky, Lauren; Hahn, Cosmo; Riley, Rebeccah; Balough, Julia; Zaza, Giuliana; Soygur, Bikem; Hung, Kaitlyn; Prado, Leandro; Kasler, Herbert G.; Tiwari, Ritesh; Matsui, Hiroyuki; Hormazabal, Genesis Vega; Heckenbach, Indra ; Scheibye-Knudsen, Morten; Duncan, Francesca E.; Verdin, Eric.

In: iScience, Vol. 26, No. 10, 107949, 2023.

Research output: Contribution to journal › Journal article › peer-review

Perrone, R, Ashok Kumaar, PV, Haky, L, Hahn, C, Riley, R, Balough, J, Zaza, G, Soygur, B, Hung, K, Prado, L, Kasler, HG, Tiwari, R, Matsui, H, Hormazabal, GV, Heckenbach, I , Scheibye-Knudsen, M, Duncan, FE & Verdin, E 2023, 'CD38 regulates ovarian function and fecundity via NAD⁺ metabolism', iScience, vol. 26, no. 10, 107949. https://doi.org/10.1016/j.isci.2023.107949

Perrone, Rosalba ; Ashok Kumaar, Prasanna Vadhana ; Haky, Lauren ; Hahn, Cosmo ; Riley, Rebeccah ; Balough, Julia ; Zaza, Giuliana ; Soygur, Bikem ; Hung, Kaitlyn ; Prado, Leandro ; Kasler, Herbert G. ; Tiwari, Ritesh ; Matsui, Hiroyuki ; Hormazabal, Genesis Vega ; Heckenbach, Indra ; Scheibye-Knudsen, Morten ; Duncan, Francesca E. ; Verdin, Eric. / CD38 regulates ovarian function and fecundity via NAD⁺ metabolism. In: iScience. 2023 ; Vol. 26, No. 10.

@article{3f82d96ac25f420a96b6a429f828d404,

title = "CD38 regulates ovarian function and fecundity via NAD+ metabolism",

abstract = "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.",

keywords = "Biochemistry, Biological sciences, Physiology",

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

note = "Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

doi = "10.1016/j.isci.2023.107949",

language = "English",

volume = "26",

journal = "iScience",

issn = "2589-0042",

publisher = "Elsevier",

number = "10",

}

TY - JOUR

T1 - CD38 regulates ovarian function and fecundity via NAD+ metabolism

AU - Perrone, Rosalba

AU - Ashok Kumaar, Prasanna Vadhana

AU - Haky, Lauren

AU - Hahn, Cosmo

AU - Riley, Rebeccah

AU - Balough, Julia

AU - Zaza, Giuliana

AU - Soygur, Bikem

AU - Hung, Kaitlyn

AU - Prado, Leandro

AU - Kasler, Herbert G.

AU - Tiwari, Ritesh

AU - Matsui, Hiroyuki

AU - Hormazabal, Genesis Vega

AU - Heckenbach, Indra

AU - Scheibye-Knudsen, Morten

AU - Duncan, Francesca E.

AU - Verdin, Eric

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - Biochemistry

KW - Biological sciences

KW - Physiology

U2 - 10.1016/j.isci.2023.107949

DO - 10.1016/j.isci.2023.107949

M3 - Journal article

C2 - 37822499

AN - SCOPUS:85172884910

VL - 26

JO - iScience

JF - iScience

SN - 2589-0042

IS - 10

M1 - 107949

ER -