Melin Vanessa E, Hrubec Terry C
Department of Biomedical Sciences and Pathobiology, VA-MD College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
Edward Via College of Osteopathic Medicine Virginia Campus, Blacksburg, VA 24060, USA.
Toxics. 2025 Aug 23;13(9):709. doi: 10.3390/toxics13090709.
Quaternary ammonium compounds (QACs) are a class of chemicals used for their antimicrobial, surfactant, and antistatic properties. QACs are present in many consumer products, and people are regularly exposed to them. We have previously shown reproductive toxicity in mice exposed to the disinfectants alkyl dimethyl benzyl ammonium chloride (ADBAC) and dodecyl dimethyl ammonium chloride (DDAC). To assess the long-term reproductive impacts, a generational reproductive study was conducted. Sperm parameters were determined by CASA and epigenetic enzyme mRNA expression was determined by pathway-focused RT-PCR. Mice ambiently exposed to ADBAC+DDAC exhibited decreases in reproductive indices that persisted through the F1 generation. Male mice (F0) dosed with 120 mg/kg/day of ADBAC+DDAC exhibited decreased sperm concentration and motility that persisted through the F1 generation. Changes in the mRNA expression of chromatin-modifying enzymes in the testes were seen. Two histone acetyltransferases (Hat1 and Kat2b) were upregulated, and one lysine-specific demethylase (Kdm6b) was downregulated in the F0 generation. The DNA methyltransferase Dnmt1 was downregulated in F1 males. These changes in chromatin-modifying enzymes are known to decrease fertility and could be a mechanism for ADBAC+DDAC reproductive toxicity. In all experiments, the F2 generation was similar to the controls, showing multi-generational but not trans-generational epigenetic inheritance.
季铵化合物（QACs）是一类因其抗菌、表面活性剂和抗静电特性而被使用的化学品。QACs存在于许多消费品中，人们经常接触到它们。我们之前已表明，暴露于消毒剂烷基二甲基苄基氯化铵（ADBAC）和十二烷基二甲基氯化铵（DDAC）的小鼠具有生殖毒性。为了评估长期生殖影响，我们进行了一项多代生殖研究。通过计算机辅助精子分析（CASA）测定精子参数，并通过靶向通路的逆转录聚合酶链反应（RT-PCR）测定表观遗传酶mRNA表达。环境暴露于ADBAC + DDAC的小鼠生殖指数下降，这种情况持续到F1代。以120 mg/kg/天的剂量给予ADBAC + DDAC的雄性小鼠（F0）精子浓度和活力下降，这种情况持续到F1代。在睾丸中观察到染色质修饰酶的mRNA表达发生变化。在F0代中，两种组蛋白乙酰转移酶（Hat1和Kat2b）上调，一种赖氨酸特异性去甲基化酶（Kdm6b）下调。DNA甲基转移酶Dnmt1在F1代雄性小鼠中下调。已知这些染色质修饰酶的变化会降低生育能力，并且可能是ADBAC + DDAC生殖毒性的一种机制。在所有实验中，F2代与对照组相似，显示出多代而非跨代的表观遗传遗传。
