Oxidative and Endoplasmic Reticulum Stress in Response to Reproduction in the Female Mouse Brain

Abstract

Reproduction is associated with a significant increase in energetic demand, particularly among small female mammals. When these demands are high, or an animal is under stress, the cost of reproduction can reduce future reproductive performance and longevity. An increase in reactive oxygen species (ROS) levels during reproduction has been proposed to drive this relationship. While empirical tests of this theory have been equivocal, relatively few studies have evaluated changes in oxidative stress within the brain and its impact on longevity. Prolonged exposure to excessive levels of ROS has been shown to impair cognitive ability, and correlations have also been found in humans between the number of offspring women have produced and the risk of developing neurological disorders. Endoplasmic reticulum stress has also been linked to oxidative stress and neurodegenerative disorders. These correlations suggest that there is a link between parity and brain damage over a lifetime. The goal of this study was to determine how reproductive experience impacted the brain by comparing mitochondrial density, oxidative damage, antioxidants and the linked, endoplasmic reticulum stress in the cerebrum, brainstem, and cerebellum of 3 groups of ICR lab mice. These age-matched mice include 1) a group of non-reproductive mice, 2) a group of mice that had one reproductive event, and 3) a group of mice that had four reproductive events. There were no significant differences found with oxidative damage markers or markers of endoplasmic reticulum induced apoptosis between reproductive groups in all brain regions, suggesting that the brain is highly resistant to oxidative stress, even under conditions of high reproductive demand. However, there was a decrease in mitochondrial density in the cerebrum of all animals that reproduced and a reduction in GPX1 levels in four-bout versus one-bout females in the cerebrum and cerebellum.