Developmental exposure to endocrine disrupting chemicals (EDCs), e.g., bisphenol A (BPA) or genistein (GEN), causes longstanding epigenome effects. MicroRNAs (miRs) regulate which mRNAs will be translated to proteins and thereby serve as the final checkpoint in epigenetic control. Scant amount is known, however, whether EDCs affect neural miRNA (miR) patterns. We aimed to test the hypothesis that developmental exposure of California mice (Peromyscus californicus) to GEN, BPA, or both chemicals influences hypothalamic miR/small RNA profiles and ascertain the extent such biomolecular alterations correlate with behavioral and metabolic changes. California mice were developmentally exposed to GEN (250 mg/kg feed weight, FW), GEN (250 mg/kg FW)+BPA (5 mg/kg FW), low dose (LD) BPA (5 mg/kg FW), or upper dose (UD) BPA (50 mg/kg FW). Adult offspring were tested in a battery of behavioral and metabolic tests; whereupon, mice were euthanized, brains were collected and frozen, small RNAs were isolated from hypothalamic punches, and subsequently sequenced. California mice exposed to one or both EDCs engaged in one or more repetitive behaviors. GEN, LD BPA, and UD BPA altered aspects of ultrasonic and audible vocalizations. Each EDC exposure led to sex-dependent differences in differentially expressed miR/small RNAs with miR7–2, miR146, and miR148a being increased in all female and male EDC exposed groups. Current findings reveal that developmental exposure to GEN and/or BPA affects hypothalamic miR/small RNA expression patterns, and such changes correlate with EDC-induced behavioral and metabolic alterations. miR146 is likely an important mediator and biomarker of EDC exposure in mammals, including humans.

发育暴露于内分泌干扰化学品 (EDC)，例如双酚 A (BPA) 或染料木黄酮 (GEN)，会导致长期的表观基因组效应。MicroRNAs (miRs) 调节哪些 mRNAs 将被翻译成蛋白质，从而作为表观遗传控制的最终检查点。然而，EDCs 是否影响神经 miRNA (miR) 模式的数量很少。我们的目的是检验加利福尼亚小鼠 ( Peromyscus californicus ) 发育暴露的假设) 到 GEN、BPA 或这两种化学物质都会影响下丘脑 miR/小 RNA 谱，并确定这种生物分子改变与行为和代谢变化相关的程度。加利福尼亚小鼠发育性暴露于 GEN（250 mg/kg 饲料重量，FW）、GEN（250 mg/kg FW）+BPA（5 mg/kg FW）、低剂量（LD）BPA（5 mg/kg FW）、或高剂量 (UD) BPA (50 mg/kg FW)。成年后代接受了一系列行为和代谢测试；随后，对小鼠实施安乐死，收集并冷冻大脑，从下丘脑穿孔中分离出小 RNA，然后对其进行测序。暴露于一种或两种 EDC 的加利福尼亚小鼠从事一种或多种重复行为。GEN、LD BPA 和 UD BPA 改变了超声波和可听发声的各个方面。每次 EDC 暴露导致差异表达的 miR/小 RNA 的性别依赖性差异，其中 miR7-2、miR146 和 miR148a 在所有女性和男性 EDC 暴露组中均增加。目前的研究结果表明，发育暴露于 GEN 和/或 BPA 会影响下丘脑 miR/small RNA 表达模式，并且这些变化与 EDC 诱导的行为和代谢改变相关。miR146 可能是哺乳动物（包括人类）中 EDC 暴露的重要介质和生物标志物。