Maternal exposure to imazalil disrupts the endocrine system in F₁ generation mice

The fungicide imazalil (IMZ), an AR antagonist, has been linked to endocrine disruption in animals. Here, adult female C57BL/6 mice were administered IMZ through their drinking water at levels of 0, 0.025‰ and 0.25‰ during the gestation and lactation periods (the exposed females are marked as F₀, and the offspring are marked as F₁). Then, we evaluated the physiological, biochemical and gene expression levels in mice after maternal IMZ exposure. The genes involved in sex hormone receptors, cholesterol synthesis and T synthesis were generally inhibited, and the serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels were also decreased in the F₀ generation female mice. In addition, after F₀ IMZ exposure, ovarian androgen receptor (AR) expression was significantly inhibited, and the androgen levels in the serum increased significantly. This may lead to the appearance of progressive virilization during pregnancy. This phenomenon leads to an aromatase deficiency in the F₁ generation mice, which results in a decrease in androgen conversion into estrogen and androgen accumulation. In addition, the mRNA expression of key genes and the serum TC, HDL-C, and LDL-C levels increased in the F₁ generation after maternal exposure to IMZ. In addition, testicular TC and LDL-C levels also decreased in the F₁ generation male mice. Molecular docking analysis revealed that key hydrogen bonds were formed by nitrogen atoms of the imidazole bonds with Trp751 of the ARs. Our data suggests that maternal IMZ exposure could induce endocrine disruption in the next generation of mice.