Exposure to first line anti-tuberculosis drugs in prepubertal age reduces the quality and functional competence of spermatozoa and oocytes in Swiss albino mice

Environ Toxicol Pharmacol. 2020 Jan;73:103292. doi: 10.1016/j.etap.2019.103292. Epub 2019 Nov 6.

Abstract

Prepubertal Swiss albino mice of both sex were administered with first-line anti-tuberculosis drugs (ATDs) viz; rifampicin, isoniazid, pyrazinamide, streptomycin and ethambutol intraperitoneally, for 4 weeks. Two weeks after the completion of treatment, male mice were sacrificed to collect caudal spermatozoa and female mice were superovulated with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) to collect metaphase II (MII) oocytes from oviduct. Administration of ATDs not only decreased the count, motility and, nuclear maturity and also, increased the head abnormalities, mitochondrial damage and DNA damage in epididymal spermatozoa. Reduction in number of ovulated oocytes, increased degeneration rate and altered distribution pattern of cytoplasmic organelles was observed in oocytes of female mice. Presence of ATDs in in vitro maturation (IVM) medium increased abnormalities in meiotic resulted in abnormal spindle organization (except ethambutol) without affecting nuclear maturation. In conclusion, the result of this study indicates that ATDs have considerable adverse effects on the functional competence of male and female gametes, however, with varied degree of toxicity.

Keywords: Anti-tuberculosis drugs; Oocyte; Ovarian toxicity; Spermatozoa; Spindle damage; Testicular toxicity.

MeSH terms

  • Animals
  • Antitubercular Agents / toxicity*
  • Cell Nucleus
  • Ethambutol / toxicity
  • Female
  • Isoniazid / toxicity
  • Male
  • Metaphase
  • Mice
  • Oocytes / drug effects*
  • Pharmaceutical Preparations
  • Pregnancy
  • Pyrazinamide / toxicity
  • Rifampin / toxicity
  • Spermatozoa / drug effects*
  • Streptomycin / toxicity

Substances

  • Antitubercular Agents
  • Pharmaceutical Preparations
  • Pyrazinamide
  • Ethambutol
  • Isoniazid
  • Rifampin
  • Streptomycin