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

Copyright © 2019 Elsevier B.V. All rights reserved..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2019

Erschienen:

2019

Enthalten in:

Zur Gesamtaufnahme - volume:486

Enthalten in:

Molecular and cellular endocrinology - 486(2019) vom: 15. Apr., Seite 105-112

Sprache:

Englisch

Beteiligte Personen:

Jin, Cuiyuan [VerfasserIn]
Zhang, Rui [VerfasserIn]
Fu, Zhengwei [VerfasserIn]
Jin, Yuanxiang [VerfasserIn]

Links:

Volltext

Themen:

6K0NOF3XQ6
AR antagonist
Androgens
Aromatase
Aromatase deficiency
EC 1.14.14.1
Endocrine Disruptors
Enilconazole
Estrogens
Imazalil
Imidazoles
Journal Article
Lipids
Mice
Receptors, Androgen
Receptors, Estrogen
Research Support, Non-U.S. Gov't
Transgenerational endocrine disruption

Anmerkungen:

Date Completed 17.01.2020

Date Revised 17.01.2020

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.mce.2019.03.002

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM294773150