2,3',4,4',5-Pentachlorobiphenyl induces mitochondria-dependent apoptosis mediated by AhR/Cyp1a1 in mouse germ cells

J Hazard Mater. 2023 Mar 5:445:130547. doi: 10.1016/j.jhazmat.2022.130547. Epub 2022 Dec 5.

Abstract

Polychlorinated biphenyls (PCBs) are environmental organic pollutants widely used in industry that can bioaccumulate and affect the reproductive systems of male animals of different species. 2,3',4,4',5-Pentachlorobiphenyl (PCB118) is a representative of the 209 toxic PCB congeners. In this study, male mice were exposed to PCB118 at 0, 50, and 500 μg/kg/day for 35 days beginning 3-4 weeks after birth. The results of the study showed that PCB118 exposure during puberty reduced testicular quality, caused tissue damage, decreased sperm motility and sperm count, and increased malformation and testicular cell apoptosis in mice. Moreover, PCB118 increased the oxidative stress levels in sperm and testicular tissue and the expression of aryl hydrocarbon receptor (AhR) and Cyp1a1 and siginificantly decreased the level of nuclear factor-erythroid 2-related factor 2 (Nrf2). The results indicate that PCB118 can activate the AhR/Cyp1a1 pathway and inhibit Nrf2 expression to aggravate testicular oxidative stress and induce cell apoptosis, resulting in testicular and sperm quality damage.

Keywords: ICR mice; Male reproductive toxicity; PCB118; ROS; Testis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cytochrome P-450 CYP1A1 / genetics
  • Cytochrome P-450 CYP1A1 / metabolism
  • Environmental Pollutants* / metabolism
  • Environmental Pollutants* / toxicity
  • Germ Cells / metabolism
  • Male
  • Mice
  • Mitochondria / metabolism
  • NF-E2-Related Factor 2 / metabolism
  • Polychlorinated Biphenyls* / metabolism
  • Polychlorinated Biphenyls* / toxicity
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / metabolism
  • Semen
  • Sperm Motility

Substances

  • 2,3',4,4',5-pentachlorobiphenyl
  • Receptors, Aryl Hydrocarbon
  • Cytochrome P-450 CYP1A1
  • NF-E2-Related Factor 2
  • Polychlorinated Biphenyls
  • Environmental Pollutants