Effects of early life adversity on male reproductive behavior and the medial preoptic area transcriptome.

Abstract

Early life adversity can alter reproductive development in humans, changing the timing of pubertal onset and sexual activity. One common form of early adversity is limited access to resources. This adversity can be modeled in rats using the limited bedding/nesting model (LBN), in which dams and pups are placed in a low resource environment from pups'postnatal days 2-9. Our laboratory previously found that adult male rats raised in LBN conditions have elevated levels of plasma estradiol compared to control males. In females, LBN had no effect on plasma hormone levels, pubertal timing, or estrous cycle duration. Estradiol mediates male reproductive behaviors. Thus, here we compared reproductive behaviors in adult males exposed to LBN vs. control housing. LBN males acquired the suite of reproductive behaviors (mounts, intromissions, and ejaculations) more quickly than their control counterparts over 3 weeks of testing. However, there was no effect of LBN in males on puberty onset or masculinization of certain brain regions, suggesting LBN effects on estradiol and reproductive behaviors manifest after puberty. In male and female rats, we next used RNA sequencing to characterize LBN-induced transcriptional changes in the medial preoptic area (mPOA), which underlies male reproductive behaviors. LBN produced sex-specific alterations in gene expression, with many transcripts showing changes in opposite directions. Numerous transcripts altered by LBN in males are regulated by estradiol, linking hormonal changes to molecular changes in the mPOA. Pathway analysis revealed that LBN induced changes in neurosignaling and immune signaling in males and females, respectively. Collectively, these studies reveal novel neurobiological mechanisms by which early life adversity can alter reproductive strategies.