Prenatal exposure to atrazine induces cryptorchidism and hypospadias in F1 male mouse offspring

Abstract

The main objective of the present study was to determine whether prenatal exposure to atrazine could affect testicle descent and penile masculinization. Atrazine has been demonstrated with a variety of endocrine disrupting activities and reproductive toxicities. However, the effects of prenatal atrazine exposure on male offspring's genital malformation, such as hypospadias and cryptorchidism, remain poorly understood. In this study, pregnant ICR mice were gavaged from gestational day 12.5–16.5 with different doses of atrazine. Although no sign of systemic toxicity was observed in F1 male pups, prenatal exposure to 100 mg/kg/day atrazine affected penile morphology, urethral meatus position and descent of testis, and reduced anogenital distance and penile size in postnatal day 21 F1 male pups. The comparative study with an androgen receptor (AR) antagonist vinclozolin suggested that these effects of atrazine on male genital development may not be through antagonism of AR. The results also revealed that atrazine exposure significantly reduced maternal serum testosterone levels, decreased AR nuclear translocation, and altered the expression levels of developmental gene networks in developing penis of mice. Atrazine exposure also affected the expression of insulin‐like 3 (Insl3) and steroidogenic gene expression in developing reproductive tract. Therefore, our data indicate that prenatal atrazine exposure can induce hypospadias in F1 mice, likely through disruption of testosterone production, decreasing genomic androgen action, and then altering expression of developmental genes during sexual differentiation. Our data also suggest that prenatal atrazine exposure can induce cryptorchidism in F1 mice, possibly through down regulation of Insl3.

Prolonged exposure to the herbicide atrazine promotes kidney fibrosis by activating Wnt/β‐catenin signaling in rats

“…Epidemiological studies have found an increased incidence of benign or malignant diseases among workers with long‐term exposure to ATR 12 . In addition, ATR is significantly associated with morphological abnormalities of the uterus 13 and testis, 14 as well as an increased incidence of breast tumors and ovarian cancer 15 . Moreover, studies have shown that ATR causes neuroendocrine changes, 16 thus affecting the central nervous system 17 and endocrine system functions 18 …”

Integrative Review Verification of the Influence of Atrazine Exposure on Behavioral, Neurochemical and Parkinsons Disease Disorders

“…It was shown that this exposure culminated in a decrease in liver weight and changes in gene expression in the liver and testis, specifi cally in genes involved in lipid uptake and fatty acid metabolism in the liver, as well as in the conversion of androgens in the testis, exposure to atrazine decreased the concentration of epididymal sperm and the number of embryonic cells generated. In a study by Tan [82], pregnant female mice received orally diff erent doses of atrazine from DGs 12.5 to 16.5. Although no signs of systemic toxicity were seen in their male off spring, prenatal exposure to 100 mg/kg/day of atrazine aff ected penile morphology, urethral meatus position and testis descent reduced anogenital distance and penis size on Postnatal Day (DPN) 21.…”

The adverse role of endocrine disrupting chemicals in the reproductive system

“…Furthermore, prenatal exposure to environmentally relevant levels of PBDEs leads to testicular dysgenesis in male offspring, which is characterized by decreased anogenital index and testicular organ coefficient, increased incidence of cryptorchidism ( 346 ). Moreover, prenatal exposure to atrazine (ATZ), an herbicide used for preventing broadleaf weeds in crops and turf grasses, was shown to induce cryptorchidism and hypospadias in male mouse offspring, potentially through the downregulation of insulin-like 3 ( 347 ). In the Norwegian HUMIS study, exposure to PCB-74, PCB-114, PCB-194, and the estrogenic organochlorine pesticide β-hexachlorocyclohexane (β-HCH) may also increase the risk of cryptorchidism ( 348 ).…”