Bisphenol A affects ovarian development in adolescent mice caused by genes expression change

Gene. 2020 May 25:740:144535. doi: 10.1016/j.gene.2020.144535. Epub 2020 Mar 7.


Many human epidemiology and animal model studies have reported that bisphenol A (BPA) exerts adverse effects on reproduction through different regulatory mechanisms and signaling pathways in adults. In recent years, the exposure risk has increased for the general population, and little is known about how BPA affects ovarian development in adolescent animals and humans. In the present study, we aimed to investigate the effects of BPA exposure on ovarian development and the transcriptome in adolescent mice. Four-week-old ICR female mice were randomly divided into two groups and orally administered BPA (200 ng/kg/day) by gavage for 4 weeks. The BPA and estrogen (E2) levels in sera from the two groups were subsequently determined by using enzyme-linked immunosorbent assays (ELISAs). An immunohistochemical study showed that several obvious ovarian structural and developmental abnormalities were observed in the treatment group with changes in the E2 receptor gene and protein expression levels. A total of 4266 differentially expressed genes (DEGs) were identified, and the possible functions of these DEGs were explored by bioinformatics analyses based on the RNA-Seq data. The two most significant expression profiles were identified by Short Time-series Expression Miner (STEM) software, and the genes in these two profiles were enriched in actin filament-based processes, behaviour and membrane potential regulation according to Gene Ontology (GO) enrichment analysis. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that these DEGs are particularly involved in the endocrine system, the calcium and cAMP signaling pathways.

Keywords: Adolescent mice; BPA exposure; Immunohistochemical observation; Ovarian development; RNA-Seq.

MeSH terms

  • Animals
  • Benzhydryl Compounds* / blood
  • Benzhydryl Compounds* / metabolism
  • Benzhydryl Compounds* / toxicity
  • Estrogen Receptor beta / genetics
  • Estrogen Receptor beta / metabolism
  • Estrogens / blood
  • Estrogens / metabolism
  • Female
  • Gene Expression Profiling
  • Immunohistochemistry
  • Mice
  • Ovary / drug effects*
  • Ovary / growth & development*
  • Ovary / ultrastructure
  • Phenols* / blood
  • Phenols* / metabolism
  • Phenols* / toxicity
  • Sexual Maturation / drug effects*


  • Benzhydryl Compounds
  • Estrogen Receptor beta
  • Estrogens
  • Phenols
  • bisphenol A