VCOM Research Day Program Book 2023

Graduate Student Research Biomedical

04 QAC Exposure Causes Infertility by Altering Endocrine Signaling and Gametogenesis

Zachary Kirkpatrick 1 , Vanessa E. Melin 1 , Terry C Hrubec 1,2 Corresponding author: zachk18@vt.edu

Virginia-Maryland College of Veterinary Medicine, Blacksburg, VA 1 Edward Via College of Osteopathic Medicine-Virginia Campus 2

Quaternary ammonium compounds (QACs) are common substances utilized throughout various industries for their antimicrobial, antistatic, and surfactant properties. QACs can be found in cleaners and disinfectants, ophthalmic solutions, swimming pool treatments, cosmetics, and a multitude of other consumer goods including hair and laundry products. Previous studies have shown that chronic QAC exposure causes infertility in both male and female mice, lowering sperm production and function in males; and reducing ovulation and implantation in females. Based on these studies, it was hypothesized that QAC exposure would negatively impact reproduction through changes in endocrine function rather than direct toxicity to gametes. To evaluate this, reproductive hormone concentrations were determined, and direct toxicity was evaluated in males through Sertoli cell function and in-vitro fertilization. Estrogen and progesterone was evaluated in dosed and un-dosed pregnant females throughout

gestation. Luteinizing hormone (LH) and follicle stimulating hormone (FSH)concentrations were determined in pre-pubertal males and females after exposure to QACs throughout gestation and lactation. Mechanisms of male reproductive ability was assessed using metabolism and viability assays, blood-testes barrier (BTB) permeability, and in-vitro fertilization capability. QAC exposure had a negative impact on endocrine hormones in both males and females. Progesterone, estrogen, LH, and FSH were lower in dosed mice compared to controls. Additionally, it was determined that QAC’s cytotoxicity at concentrations above 0.001% correlated with changes in BTB integrity indicating direct damage to the BTB. Fertilization was decreased in males only after one passage of a complete spermatogenic cycle. This suggests a direct effect on spermatogonia in the testis or disruption of spermatogenesis from endocrine dysfunction, but little direct on spermatozoa.

QACs implications on endocrine signaling and gametogenesis is an important factor to consider in rising infertility rates and increased use of assisted reproductive technologies. Due to the ubiquitous nature of QACs, it is important to investigate the effects these compounds have on health and reproduction.

This project was funded by the Summer Veterinary Student Research Program and the Passport Foundation

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