PUBLICATION

Transcriptome and in silico approaches provide new insights into the mechanism of male reproductive toxicity induced by chronic exposure to DEHP

Authors
Ma, Y.B., Manzoor, R., Jia, P.P., Bian, W.P., Hamid, N., Xie, Z.Y., Pei, D.S.
ID
ZDB-PUB-210815-6
Date
2021
Source
Environmental pollution (Barking, Essex : 1987)   289: 117944 (Journal)
Registered Authors
Bian, Wanping, Ma, Yanbo, Pei, Desheng
Keywords
Chronic exposure, DEHP, Male zebrafish, Progesterone receptor, Reproductive toxicity
MeSH Terms
  • Animals
  • Diethylhexyl Phthalate*/toxicity
  • Male
  • Molecular Docking Simulation
  • Reproduction
  • Transcriptome
  • Zebrafish/genetics
PubMed
34391046 Full text @ Environ. Pollut.
Abstract
Di-(2-ethylhexyl) phthalate (DEHP) can affect the male reproductive system in vertebrates, but the underlying molecular mechanism is still elusive. Therefore, in this study, we aimed to dig the in-depth mechanism of DEHP-induced reproductive toxicity on male zebrafish via testicular transcriptome using embryo exposed at the environmentally relevant concentration (ERC) of 100 μg/L for 111 days. Moreover, our results were further confirmed via in silico technique and bioassay experimental in vitro (cell lines) and in vivo (zebrafish). The results showed DEHP exposure could affect male spermatogenesis, altered gonad histology, and reduced egg fertilization rate. Transcriptome analysis identified 1879 significant differentially expressed genes enriched in the exposure group. Twenty-seven genes related to three pathways of reproduction behavior were further validated by qPCR. In silico molecular docking revealed that DEHP and its metabolism bind to the zebrafish progesterone receptor (Pgr), suggesting the potential disruption of DEHP to the normal Pgr signaling. To further validate it, a wild-type Pgr plasmid and its mutants on specific binding sites were constructed. The transfection and microinjection experiment demonstrated that these binding sites mutations of Pgr affected the expression levels of male reproductive toxicity. Taken together, our study provided new insight into the molecular mechanisms of male reproductive toxicity induced by DEHP, and Pgr may serve as an important target binding by DEHP pollution, which needs further study in the future.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping