Chlorothalonil inhibits mouse ovarian development through endocrine disruption

Toxicol Lett. 2019 Mar 15:303:38-47. doi: 10.1016/j.toxlet.2018.12.011. Epub 2018 Dec 23.

Abstract

Although many studies have investigated the toxic effects and even the reproductive toxicity of chlorothalonil, almost no studies have focused on the ovary, the organ of oocyte development. Puberty is a critical window for development of the female reproductive system. Therefore, this investigation aimed to explore the effects and underlying mechanisms of chlorothalonil at low doses on peripubertal mouse ovarian development. Chlorothalonil is frequently used in horticulture with short intervals between applications, therefore, vegetables and fruits may be potential sources of chlorothalonil contamination. For the first time, this study demonstrated that chlorothalonil inhibited ovarian development during puberty in mice, and at levels currently assumed to have no adverse health consequences for humans. Chlorothalonil exposure inhibited mouse ovarian development by increasing the number of primary follicles and decreasing the number of mature follicles. It acted by decreasing the levels of hormone production proteins, such as FSH receptor and estrogen receptor alpha, while increasing the levels of DNA repairing marker RAD51 and cell apoptosis. These results suggest that chlorothalonil may disrupt endocrine function and inhibit murine ovarian development. Therefore it may pose a potential health risk to female reproductive systems in other species, especially to the ovary.

Keywords: Chlorothalonil; Development; Endocrine disrupting; Ovary; Pubertal.

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Apoptosis / drug effects
  • Aspartate Aminotransferases / blood
  • DNA Damage
  • DNA Repair
  • ERRalpha Estrogen-Related Receptor
  • Endocrine Disruptors / toxicity*
  • Female
  • Genetic Markers
  • Gonadal Steroid Hormones / blood
  • Mice
  • Mice, Inbred ICR
  • Nitriles / toxicity*
  • Oogenesis / drug effects*
  • Ovarian Follicle / cytology
  • Ovarian Follicle / drug effects*
  • Ovarian Follicle / metabolism
  • Rad51 Recombinase / genetics
  • Rad51 Recombinase / metabolism
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism
  • Receptors, FSH / genetics
  • Receptors, FSH / metabolism
  • Reproduction / drug effects

Substances

  • Endocrine Disruptors
  • Genetic Markers
  • Gonadal Steroid Hormones
  • Nitriles
  • Receptors, Estrogen
  • Receptors, FSH
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Rad51 Recombinase
  • Rad51 protein, mouse
  • tetrachloroisophthalonitrile