Molecular Analysis of a Paternally Transmitted Placental Phenotype in a Mouse Model of Paternal Alcohol Exposure

Abstract

This project investigates the reason why the placentas of mice sired by males exposed to alcohol prior to conception are larger and less efficient than placentas of control mice. This research question is important because it will help explain how preconception paternal alcohol exposure (PAE) influences the health and development of offspring, including symptoms such as low birth weight and metabolic irregularities. Research in the Golding lab has demonstrated that preconception paternal alcohol exposure is associated with a reduction in placental efficiency, however, the mechanism behind the enlargement of the placenta and reduction in placental efficiency is still unknown. To address this question, we assayed the impact of paternal drinking on an outbred cross and followed these experiments with an analysis of placental gene expression. Here, we find that differences in placental efficiency after preconception PAE are sex-specific as well as maternal-strain specific. Interestingly, the male offspring of alcohol-exposed males mated to C57BL6/J dams exhibited decreased placental efficiency, while in contrast, male offspring of alcohol-exposed males mated to ICR dams displayed increased placental efficiency. This suggests that the maternal uterine environment or fetal genetics play a role in how the placenta develops in response to preconception PAE. Additionally, RT-qPCR was performed on placental samples in order to identify differentially expressed genes hypothesized to be involved with the observed placental phenotype. The genes encoding retinoid X receptor α (RXRα) and farnesoid X-activated receptor (FXR) were significantly upregulated in the placentas of female offspring sired by alcohol-exposed males mated to C57BL6/J dams. Since these genes are involved in placental development and lipid metabolism, it is possible that the upregulation of these genes allowed these alcohol-sired females to avoid decreased placental efficiency as seen in their male counterparts.