Fig. 3: CD38 deletion increased ovarian NAD+ levels and improved ovarian follicle reserve, increased reproductive ability of aging mice and shifted the ovarian transcriptome toward a more youthful profile.
a, Ovarian NAD+ levels in WT and Cd38−/− mice at different ages (n = 6 mice for each group). b, Ovarian weight changes during aging in WT and Cd38−/− mice (n = 7 mice for each group). c, Mean serum AMH levels assessed by an ELISA in ovaries from 8-month-old and 12-month-old WT and Cd38−/− mice (n = 4 or 5 mice for each group). d, Mean litter size from WT and Cd38−/− mice (n = 25 mice for 2–6 months in each group, n = 18 for 7–9 months in WT group, n = 8 for 7–9 months in Cd38−/− group, n = 9 for 10–12 months in WT group, n = 12 for 10–12 months in Cd38−/− group). e, Representative hematoxylin-and-eosin-stained ovarian sections from 2-month-old, 8-month-old and 12-month-old WT and Cd38−/− mice. Scale bar, 100 μm. f–h, Numbers of ovarian follicles at different stages, including the primordial follicle (PMF), the primary follicle (PF), the secondary follicle (SF) and the antral follicle (AF), were monitored in WT and Cd38−/− mice at different ages (2 months (f), 8 months (g), 12 months (h)) (n = 5 or 6 mice for each group). i, Heat map of ovarian DEGs between 2-month-old and 8-month-old mice, together with those genes expressed in 8-month-old Cd38−/− mice. Genes with log2FC > 1 and adjusted P value (by the Benjamini–Hochberg method) < 0.05 were considered DEGs (n = 5 ovaries for each group). j,k, GO analysis identified downregulated (j) and upregulated (k) genes in different pathways between 8-month-old WT and Cd38−/− mice. P values were calculated by Fisher’s exact test. l, Heat map showing the DEGs in the ‘cell cycle’, ‘DNA repair’, ‘inflammation’ and ‘SASP’ pathways in ovaries from 2-month-old WT as well as 8-month-old WT and Cd38−/− mice. Data are presented as the mean ± s.e.m. P value was determined by the unpaired, two-tailed t-test between the two groups.
