CD38 regulates ovarian function and fecundity via NAD+ metabolism
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, an NAD+ consuming enzyme, is expressed...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-10-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223020266 |
| _version_ | 1797647842601336832 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Rosalba Perrone |
| collection | DOAJ |
| description | 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, 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. |
| first_indexed | 2024-03-11T15:22:21Z |
| format | Article |
| id | doaj.art-b684e354f37142c3801059b7ca25046d |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-11T15:22:21Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-b684e354f37142c3801059b7ca25046d2023-10-28T05:09:05ZengElsevieriScience2589-00422023-10-012610107949CD38 regulates ovarian function and fecundity via NAD+ metabolismRosalba Perrone0Prasanna Vadhana Ashok Kumaar1Lauren Haky2Cosmo Hahn3Rebeccah Riley4Julia Balough5Giuliana Zaza6Bikem Soygur7Kaitlyn Hung8Leandro Prado9Herbert G. Kasler10Ritesh Tiwari11Hiroyuki Matsui12Genesis Vega Hormazabal13Indra Heckenbach14Morten Scheibye-Knudsen15Francesca E. Duncan16Eric Verdin17Buck Institute for Research on Aging, Novato, CA, USABuck Institute for Research on Aging, Novato, CA, USABuck Institute for Research on Aging, Novato, CA, USA; The Dominican University of California, San Rafael, CA, USABuck Institute for Research on Aging, Novato, CA, USABuck Institute for Research on Aging, Novato, CA, USABuck Institute for Research on Aging, Novato, CA, USABuck Institute for Research on Aging, Novato, CA, USABuck Institute for Research on Aging, Novato, CA, USABuck Institute for Research on Aging, Novato, CA, USABuck Institute for Research on Aging, Novato, CA, USABuck Institute for Research on Aging, Novato, CA, USABuck Institute for Research on Aging, Novato, CA, USABuck Institute for Research on Aging, Novato, CA, USABuck Institute for Research on Aging, Novato, CA, USACenter for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, DenmarkCenter for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, DenmarkBuck Institute for Research on Aging, Novato, CA, USA; Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Corresponding authorBuck Institute for Research on Aging, Novato, CA, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004223020266Biological sciencesBiochemistryPhysiology |
| spellingShingle | 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 CD38 regulates ovarian function and fecundity via NAD+ metabolism iScience Biological sciences Biochemistry Physiology |
| title | CD38 regulates ovarian function and fecundity via NAD+ metabolism |
| title_full | CD38 regulates ovarian function and fecundity via NAD+ metabolism |
| title_fullStr | CD38 regulates ovarian function and fecundity via NAD+ metabolism |
| title_full_unstemmed | CD38 regulates ovarian function and fecundity via NAD+ metabolism |
| title_short | CD38 regulates ovarian function and fecundity via NAD+ metabolism |
| title_sort | cd38 regulates ovarian function and fecundity via nad metabolism |
| topic | Biological sciences Biochemistry Physiology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223020266 |
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