Abstract
Glucocorticoid exposure during pregnancy have multigenerational effects on neuroendocrine function and behaviours in offspring. Importantly, effects are transmitted through the paternal lineage. Altered phenotypes are associated with profound differences in transcription and DNA methylation in the brain. In the present study, we hypothesized that maternal prenatal synthetic glucocorticoid (sGC) exposure in the F0 pregnancy will result in differences in miRNA levels in testicular germ cells and sperm across multiple generations, and that these changes will associate with modified miRNA profiles and gene expression in the prefrontal cortex of subsequent generations. Pregnant female guinea pigs (F0) were treated multiple courses of sGC in late gestation. miRNA levels were assessed in testes germ cells using the miRNA Array, and candidate miRNA measured in epididymal sperm by qRT-PCR. Maternal sGC exposure did not alter miRNA levels in germ cells derived from the testes of adult male offspring. However, there were significant differences in the levels four candidate miRNAs in the sperm of F1 and F2 adult males. This study has identified that maternal sGC exposure leads to altered miRNA levels in sperm that are apparent for at least two generations.
