Expression of the placental transcriptome in fetal growth restriction in the Baboon is Dependent on Fetal Sex

Fetal growth restriction (FGR) develops when fetal nutrient availability is compromised and increases the risk for perinatal complications and predisposes for offspring obesity, diabetes and cardiovascular disease later in life. Emerging evidence implicates changes in placental function in altered fetal growth and the subsequent development of adult disease. The susceptibility for disease in response to an adverse intrauterine environment differs distinctly between boys and girls, with girls typically having better outcomes. Here, we test the hypothesis that regulation of the placental transcriptome by moderate nutrient reduction is dependent on fetal sex. We used a non-human primate model of FGR in which maternal global food intake is reduced by 30% starting at gestational day (GD) 30. At GD 165 (term = GD 183) placental genome expression profiling was carried out followed by bioinformatics including pathway and network analysis. Surprisingly, there was no coordinated placental molecular response to decreased nutrient availability when analyzing the data without accounting for fetal sex. In contrast, female placentas exhibited a highly coordinated response that included up-regulation of genes in networks, pathways and functional groups related to programmed cell death and down-regulation of genes in networks, pathways and functional groups associated with cell proliferation. These changes were not apparent in the male placentas. Our data support the concept that female placentas initiate complex adaptive responses to an adverse intrauterine environment, which may contribute to increased survival and better pregnancy outcomes in girls. Total RNA obtained from 165dGA control female (n=3), control male (n=3), nutrient restricted female (n=3), and nutrient restricted male (n=3) pregnancies.