K. Selesniemi, H-J. Lee, A. Muhlhauser, P. Hunt, J.L. Tilly

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Introduction: The decline in ovarian function and female fertility with age are driven by depletion of the oocyte (germ cell)-containing follicle reserve as well as a marked increase in chromosomal abnormalities that arise due to meiotic errors. This latter issue elevates the risk for aneuploid conception in women in the late 30s and early 40s, resulting in embryonic failure, miscarriage and birth defects. As more women are having children later in life, strategies to safely maintain ovarian function and oocyte quality with age are needed. While little at present can be done in this regard in women, our previous studies with mice showed that adult-onset caloric restriction (CR) sustains female fertility well past the age at which ad libitum (AL)-fed females became infertile (Aging Cell 2008 7:622-629). Fecundity and postnatal offspring survival were also maintained by CR, suggesting that CR may offset the age-related decline in oocyte quantity and quality. Objective: To directly assess the effects of adult-onset CR on oocyte quantity and quality in aged female mice. Methods: Female C57BL/6 mice were kept on AL or 40% CR diets from 4 to 11 months of age, at which time AL-feeding was resumed in CR cohorts. At 12 months (12-mo), ovarian stimulation with exogenous hormones was performed to induce superovulation (in effect, mimicking clinical in vitro fertilization procedures) and oocytes were collected from the oviducts. For each female, the total number of oocytes ovulated and the maturational stage of each oocyte was recorded, and in vitro fertilization was performed to assess developmental competency. In parallel experiments, chromosome spreads from individual oocytes were analyzed for evidence of aneuploidy. Young AL-fed females at peak reproductive age (3 months, 3-mo) were analyzed in parallel for comparison. Results: Fewer oocytes were obtained from 12-mo AL-fed mice (n = 12) than from 3-mo females (n = 6) (6.5 ± 2.1 versus 26.3 ± 4.6 per female, respectively; P

Keywords (Optional): 
caloric restriction