Kirkpatrick Zachary A, Melin Vanessa E, Hrubec Terry C
VA-MD Regional College of Veterinary Medicine, VA Tech, Blacksburg, VA 24061, USA.
VA-MD Regional College of Veterinary Medicine, VA Tech, Blacksburg, VA 24061, USA; E. Via College of Osteopathic Medicine Virginia Campus, Blacksburg, VA 24060, USA.
Reprod Toxicol. 2025 Mar;132:108817. doi: 10.1016/j.reprotox.2024.108817. Epub 2024 Dec 7.
Quaternary ammonium compounds (QACs) are common substances utilized in cleaners, ophthalmic solutions, swimming pool treatments, cosmetics, and other consumer goods. Previous studies have shown that QAC exposure causes infertility in both male and female mice. Based on these studies, we hypothesized that oral QAC exposure negatively impacts male and female reproduction through changes in physiologic and endocrine mechanisms rather than direct toxicity to gametes. Endocrine disruption was assessed by evaluating luteinizing hormone (LH) and follicle stimulating hormone (FSH) concentrations in male and female mice exposed orally throughout gestation and lactation, and by changes in estrogen and progesterone in in orally exposed females throughout pregnancy. Sperm functionality and spermatogenesis were assessed by in vitro fertilization; while Sertoli cell homeostasis was evaluated by determining cellular metabolism, cell cycle progression and blood-testes barrier (BTB) permeability. QAC exposure decreased LH, and FSH concentrations in both males and females, and decreased progesterone and estrogen concentrations during pregnancy. QACs significantly decreased Sertoli cell metabolism at 0.0005 % ADBAC+DDAC well before disruption of the BTB at 0.01 %. Fertilization was not affected 24 h after exposure but was decreased after a 10 day rest period suggesting a disruption in spermatogenesis rather than direct toxicity to sperm. Lastly, QAC exposure altered Sertoli cell cycling with a G2/M cycle arrest. While the effect of QAC exposure on humans is unknown, implications from the in vivo and in vitro studies are concerning given the rise in infertility rates and increased reliance on assisted reproductive technologies along with ubiquitous exposure to QACs.
季铵化合物（QACs）是清洁用品、眼科溶液、泳池处理剂、化妆品及其他消费品中常用的物质。先前的研究表明，接触QACs会导致雄性和雌性小鼠不育。基于这些研究，我们推测口服QACs通过生理和内分泌机制的改变对雄性和雌性生殖产生负面影响，而非对配子的直接毒性。通过评估在整个妊娠期和哺乳期口服暴露的雄性和雌性小鼠中促黄体生成素（LH）和促卵泡生成素（FSH）的浓度，以及在整个孕期口服暴露的雌性小鼠中雌激素和孕酮的变化来评估内分泌干扰情况。通过体外受精评估精子功能和精子发生；通过测定细胞代谢、细胞周期进程和血睾屏障（BTB）通透性来评估支持细胞的内环境稳定。QACs暴露降低了雄性和雌性小鼠的LH和FSH浓度，并降低了孕期的孕酮和雌激素浓度。在0.01%时BTB破坏之前，0.0005%的十二烷基二甲基苄基氯化铵+二癸基二甲基氯化铵（ADBAC+DDAC）就显著降低了支持细胞的代谢。暴露24小时后受精未受影响，但在休息10天后受精率下降，这表明精子发生受到干扰，而非对精子的直接毒性。最后，QACs暴露使支持细胞周期改变，出现G2/M期阻滞。虽然QACs暴露对人类的影响尚不清楚，但鉴于不孕率上升、对辅助生殖技术的依赖增加以及QACs无处不在的暴露，体内和体外研究的结果令人担忧。
