Tributyltin and the Female Hypothalamic-Pituitary-Gonadal Disruption

Kayke L. Barbosa, Raquel S. Dettogni, Charles S. Da Costa, Eduardo L. Gastal, Lori T. Raetzman, Jodi A. Flaws, Jones B. Graceli

Research output: Contribution to journalReview articlepeer-review


The hypothalamic-pituitary-gonadal (HPG) axis is the principal modulator of reproductive function. Proper control of this system relies on several hormonal pathways, which make the female reproductive components susceptible to disruption by endocrine-disrupting chemicals such as tributyltin (TBT). Here, we review the relevant research on the associations between TBT exposure and dysfunction of the female HPG axis components. Specifically, TBT reduced hypothalamic gonadotropin-releasing hormone (GnRH) expression and gonadotropin release, and impaired ovarian folliculogenesis, steroidogenesis, and ovulation, at least in part, by causing abnormal sensitivity to steroid feedback mechanisms and deleterious ovarian effects. This review covers studies using environmentally relevant doses of TBT in vitro (1 ng - 20 ng/ml) and in vivo (10 ng - 20 mg/kg) in mammals. The review also includes discussion of important gaps in the literature and suggests new avenue of research to evaluate the possible mechanisms underlying TBT-induced toxicity in the HPG axis. Overall, the evidence indicates that TBT exposure is associated with toxicity to the components of the female reproductive axis. Further studies are needed to better elucidate the mechanisms through which TBT impairs the ability of the HPG axis to control reproduction.

Original languageEnglish (US)
Pages (from-to)179-189
Number of pages11
JournalToxicological Sciences
Issue number2
StatePublished - Apr 1 2022


  • endocrine-disrupting chemicals
  • female
  • hypothalamic-pituitary-gonadal axis
  • ovary
  • tributyltin

ASJC Scopus subject areas

  • Toxicology


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