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  3. The effect of 3-Methyl-4-Nitrophenol on the early ovarian follicle development in mice by disrupting the clock genes expression

The effect of 3-Methyl-4-Nitrophenol on the early ovarian follicle development in mice by disrupting the clock genes expression

  • Chem Biol Interact. 2022 Aug 25:363:110001. doi: 10.1016/j.cbi.2022.110001.
Sijie Fan 1,  Xinyu Zhao 1,  Wenqian Xie 1,  Xiaoying Yang 1,  Wenyang Yu 1,  Zeqi Tang 1,  Yuan Chen 1,  Zhengrong Yuan 1,  Yingying Han 1,  Xia Sheng 2,  Haolin Zhang 3,  Qiang Weng 1
Affiliations

Affiliations

  • 1 College of Biological Science and Technology, Beijing Forestry University, Beijing, 100083, China.
  • 2 Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, And State Key Laboratory of Environmental Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
  • 3 College of Biological Science and Technology, Beijing Forestry University, Beijing, 100083, China. Electronic address: haolinzhang@bjfu.edu.cn.
PMID: 35654127 DOI: 10.1016/j.cbi.2022.110001
Abstract

3-Methyl-4-Nitrophenol (PNMC) is the main degradation product of organophosphate insecticide fenitrothion and a major component of diesel exhaust particles, which is now becoming a widely spread environmental endocrine disruptor. Previous reports showed PNMC exposure can affect the female reproductive system and ovarian function; however, the mechanism remains unclear. The main purpose of this study is to clarify the mechanism underlying the adverse effects of neonatal PNMC treatment on ovarian functions. The neonatal female mice were exposed to 10 mg/kg PNMC and the ovaries were collected on the 7th day after birth. The changes of follicular composition in mice ovaries were analyzed by histological staining, which showed that the proportion of primordial follicles in the ovaries treated by PNMC decreased, while the proportion of secondary follicles increased. The ovarian function was also investigated by detecting the expressions of steroidogenic Enzymes (Star, Cyp11a1, Hsd3b1, CYP17A1, Cyp19a1), gonadotropin receptors (Fshr and Lhr), Androgen Receptor (Ar), and estrogen receptors (Esr1 and Esr2) by immunohistochemistry or/and real-time quantitative PCR. The expression of Hsd3b1, CYP17A1 and Esr2 were increased significantly in the PNMC exposed ovaries. Moreover, the expression patterns of clock genes (Bmal1, Clock, Per1, Per2, Cry1, Cry2 and Nr1d1) were disrupted in the ovaries after PNMC exposure. Furthermore, either the expression of DNA Methyltransferase Dnmt3b, or the methylation ratio of CpG islands in the upstream of Cry1 promoter regions were significantly decreased in PNMC exposed ovaries. Altogether, these results indicate that PNMC exposure affects follicle development and ovarian function by interfering with the epigenetic modification and disrupting the expression of clock genes.

Keywords

3-Methyl-4-nitrophenol; Clock genes; Environmental endocrine disruptors; Methylation; Ovarian function.

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