Casciaro Christopher, Hamada Hirotaka, Kostaki Alisa, Matthews Stephen G
Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Department of Gynecology and Obstetrics, Tohoku University Graduate School of Medicine, Sendai, Japan.
FASEB J. 2023 Apr;37(4):e22879. doi: 10.1096/fj.202201784R.
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.
大约1%-3%的成年人口因各种病症接受合成糖皮质激素（sGCs）治疗。研究表明，雄性在受孕前经历的逆境可能导致后代神经内分泌功能和行为异常，精子内包括微小RNA（miRNA）在内的表观遗传因素可能是造成这些影响的原因。然而，附睾中精子miRNA变化发生的具体位置仍不清楚。在此，我们假设sGC暴露将以区域特异性方式改变附睾中精子的miRNA谱。成年雄性豚鼠每隔一天饮用普通饮用水（对照组）或含sGC地塞米松（Dex；3mg/kg）的水（每组n = 6），持续48天。从附睾头和附睾尾区域的附睾精液中收集精子并提取总RNA。通过miRNA 4.0微阵列评估miRNA；数据由TAC 4.0.1和R处理。miRNA分析显示，附睾头中的一种miRNA在精子中被Dex显著降低。在附睾尾，Dex暴露后精子中有31种miRNA减少。本研究结果表明，Dex暴露影响附睾尾而非附睾头中精子的miRNA谱。这表明糖皮质激素靶向附睾以改变精子miRNA，而不改变睾丸精子形成过程中的miRNA含量。
