PFOA-induced ovotoxicity differs between lean and obese mice with impacts on ovarian reproductive and DNA damage sensing and repair proteins
Date
2022-10-10
Authors
Major Professor
Advisor
Committee Member
Journal Title
Journal ISSN
Volume Title
Publisher
Oxford University Press
Abstract
Perfluorooctanoic acid (PFOA) is an environmentally persistent perfluoroalkyl substance that is widely used in consumer products. Exposure to PFOA is associated with reproductive and developmental effects including endocrine disruption, delayed puberty in girls, and decreased fetal growth. In the US, obesity affects 40% of women and 20% of girls, with higher rates in minority females. Obesity causes infertility, poor oocyte quality, miscarriage, and offspring defects. This study proposed that PFOA exposure would impact estrous cyclicity, ovarian steroid hormones and the ovarian proteome and further hypothesized that obesity would impact PFOA-induced ovotoxicity. Female wild type (KK.Cg-a/a; lean) or KK.Cg-Ay/J mice (obese) received saline (CT) or PFOA (2.5 mg/Kg) per os for 15 days beginning at 7 weeks of age. There were no effects on food intake, body weight, estrous cyclicity, serum progesterone, and heart, spleen, kidney, or uterus weight (P > 0.05). Ovary weight was decreased (P < 0.05) by PFOA exposure relative to vehicle control-treated mice in lean but not obese mice. LC-MS/MS was performed on isolated ovarian protein and PFOA exposure altered the ovarian abundance of proteins involved in DNA damage sensing and repair pathways and reproduction pathways (P < 0.05) differentially in lean and obese mice. The data suggest that PFOA exposure alters ovary weight and differentially targets ovarian proteins in lean and obese females in ways that might reduce female fecundity.
Series Number
Journal Issue
Is Version Of
Versions
Series
Academic or Administrative Unit
Type
article
Comments
This is a pre-copyedited, author-produced version of an article accepted for publication in Toxicological Sciences following peer review.
The version of record: González-Alvarez, M. Estefanía, Andrew Severin, Maryam Sayadi, and Aileen F. Keating. "PFOA-induced ovotoxicity differs between lean and obese mice with impacts on ovarian reproductive and DNA damage sensing and repair proteins." Toxicological Sciences (2022): kfac104 is available online at DOI: 10.1093/toxsci/kfac104.
Copyright 2022 The Author(s).
Posted with permission.