AI Article Synopsis
- Mammalian female reproductive lifespan is shorter than overall life expectancy, linked to declining ovarian NAD+ levels, but the reasons for this decline are unclear.
- Research reveals that the enzyme CD38, which consumes NAD+, is found in ovarian immune cells and its levels increase with age.
- Mice without CD38 show larger pools of primordial follicles and higher NAD+ levels, enhancing fertility in youth, but these benefits diminish as they age, highlighting CD38's role in controlling ovarian NAD+ and reproductive longevity.
Article 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.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10562803 | PMC |
| http://dx.doi.org/10.1016/j.isci.2023.107949 | DOI Listing |
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