Developmental Origins of Transgenerational Sperm DNA Methylation Epimutations Following Ancestral Vinclozolin Exposure

Previously the agricultural fungicide vinclozolin was found to promote the transgenerational inheritance of sperm differential DNA methylation regions (DMRs) termed epimutations that help mediate this epigenetic inheritance. The current study was designed to investigate the developmental origins of the transgenerational DMRs during gametogenesis. Male control and vinclozolin lineage F3 generation rats were used as a source of embryonic day 16 (E16) prospermatogonia, postnatal day 10 (P10) spermatogonia, and adult pachytene spermatocytes, round spermatids, caput epididymal sperm, and caudal sperm. The DMRs between the control versus vinclozolin lineage samples were determined for each developmental stage. The top 100 statistically significant DMRs for each stage were compared and the developmental origins of the caudal epididymal sperm DMRs were assessed.此前研究发现，农用杀菌剂乙烯菌核利（vinclozolin）可诱导精子差异DNA甲基化区域（differential DNA methylation regions, DMRs，即表观突变）的跨代遗传，此类表观突变参与介导该表观遗传过程。本研究旨在探究配子发生过程中跨代DMRs的发育起源。实验采用对照组与乙烯菌核利谱系的F3代雄性大鼠为实验材料，分别获取其胚胎第16天（E16）的前精原细胞、出生后第10天（P10）的精原细胞，以及成年个体的粗线期精母细胞、圆形精子细胞、附睾头精子与附睾尾精子。针对每个发育阶段，鉴定对照组与处理组样本间的差异DMRs；对各阶段排名前100的统计学显著DMRs进行比对分析，并评估附睾尾精子DMRs的发育起源。