Obesity alters the ovarian DNA damage response and apoptotic proteins

in Reproduction
Authors:
Kendra L Clark Department of Animal Science, Iowa State University, Ames, Iowa, USA

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Crystal M Roach Department of Animal Science, Iowa State University, Ames, Iowa, USA

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, and
Aileen F Keating Department of Animal Science, Iowa State University, Ames, Iowa, USA

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Correspondence should be addressed to A F Keating; Email: akeating@iastate.edu
DOI:
https://doi.org/10.1530/REP-20-0070
Volume/Issue:
Volume 160: Issue 5
Page Range:
751–760
Article Type:
Research Article
Online Publication Date:
Nov 2020
Copyright:
© 2020 Society for Reproduction and Fertility 2020
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In the overweight or obese female, reproductive complications include poor oocyte quality, decreased fecundity, gestational diabetes, and higher risk of reproductive cancers. Using lean and hyperphagia-induced obese female mice aged 10 weeks, we determined that the ovary from obese female mice had elevated (P < 0.10) levels of ataxia telangiectasia mutated (ATM) protein in oocytes of both small and large follicles. Phosphorylated ATM at serine 1981 was greater (P < 0.05) in large relative to small follicles with no additional impact of obesity. Obesity increased (P < 0.05) γH2AX in small follicles in obese relative to lean ovaries, while large follicles of both lean and obese mice had detectable levels of γH2AX. Cleaved caspase 3 was reduced (P < 0.05) in the small follicles of obese relative to lean ovaries. In large follicles of lean mice, cleaved caspase 3 was increased in large compared to small follicles (P < 0.05) but this pattern was absent in obese mice. Breast cancer type 1 susceptibility protein (BRCA1) or the phosphorylated BRCA1 proteins were observably altered by obesity. These data demonstrate that markers of DNA damage and repair have a follicle-dependent stage location and that obesity alters ATM and cleaved caspase 3 in a follicular stage dependent manner.

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Print ISSN:
1470-1626
Online ISSN:
1741-7899

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