Glucocorticoid exposure modifies the miRNA profile of sperm in the guinea pig: Implications for intergenerational transmission

Abstract

Approximately 1%-3% of the adult population are treated with synthetic glucocorticoids (sGCs) for a variety of conditions. Studies have demonstrated that adversities experienced by males prior to conception may lead to abnormal neuroendocrine function and behaviors in offspring and that epigenetic factors including microRNA (miRNA) within sperm may be responsible for driving these effects. However, it remains unclear where in the epididymis sperm miRNA changes are occurring. Here, we hypothesized that sGC exposure will alter the miRNA profile of sperm in the epididymis in a region-specific manner. Adult male guinea pigs were exposed to regular drinking water (Ctrl) or water with the sGC dexamethasone (Dex; 3mg/kg) (n = 6/group) every other day for 48 days.Sperms were collected from epididymal seminal fluid in the caput and cauda regions of the epididymis and total RNA was extracted. miRNAs were assessed by miRNA 4.0 microarray; data were processed by TAC 4.0.1 and R. miRNA analysis revealed one miRNA in the caput that was significantly decreased by Dex in sperm. In the cauda, 31 miRNAs were reduced in sperm following Dex-exposure.The findings of this study demonstrate that Dex-exposure influences miRNA profile of sperm in the cauda but not the caput of the epididymis. This suggests that glucocorticoids target the epididymis to modify sperm miRNA and do not modify the miRNA content during spermiation in the testes.

Prenatal maternal glucocorticoid exposure modifies sperm miRNA profiles across multiple generations in the guinea‐pig

“…Our studies suggest that the intergenerational effects of prenatal Beta (F0 pregnancy) on sperm miRNA levels may be mediated primarily in the epididymis and involve alterations in the epididymal epithelial cells and epididymosomes. In this regard, we have recently shown that the miRNA profile of cauda sperm in the epididymis is influenced following sGC exposure in adult males (Casciaro et al., 2023). These findings suggest that sGCs target the GR in the epididymis during sperm maturation rather than the testes during spermatogenesis.…”

Sowing the seeds of stress: maternal exposure to synthetic glucocorticoids impacts sperm miRNA for generations

“…The Matthews research team recently demonstrated in another study that glucocorticoids can indeed impact sperm miRNA directly. Casciaro et al (2023) provided adult male guineapigs sGC daily throughout the period of spermatogenesis and demonstrated altered miRNA profiles within sperm from the cauda of the epididymis. Hamada et al also highlighted an important association between miR-125b, which was altered across generations in the sperm, and its target gene, Itga8, in the prefrontal cortex of F 1 and F 2 female offspring.…”

“…Casciaro et al. (2023) provided adult male guineapigs sGC daily throughout the period of spermatogenesis and demonstrated altered miRNA profiles within sperm from the cauda of the epididymis.…”