Developmental exposure to the endocrine disruptor tolylfluanid induces sex-specific later-life metabolic dysfunction

Reprod Toxicol. 2019 Oct;89:74-82. doi: 10.1016/j.reprotox.2019.06.010. Epub 2019 Jun 28.

Abstract

Endocrine-disrupting chemicals (EDCs) are implicated in the developmental mis-programming of energy metabolism. This study examined the impact of combined gestational and lactational exposure to the fungicide tolylfluanid (TF) on metabolic physiology in adult offspring. C57BL/6 J dams received standard rodent chow or the same diet containing 67 mg/kg TF. Offspring growth and metabolism were assessed up to 22 weeks of age. TF-exposed offspring exhibited reduced weaning weight. Body weight among female offspring remained low throughout the study, while male offspring matched controls by 17 weeks of age. Female offspring exhibited reduced glucose tolerance, markedly enhanced systemic insulin sensitivity, reduced adiposity, and normal gluconeogenic capacity during adulthood. In contrast, male offspring exhibited impaired glucose tolerance with unchanged insulin sensitivity, no differences in adiposity, and increased gluconeogenic capacity. These data indicate that developmental exposure to TF induces sex-specific metabolic disruptions that recapitulate key aspects of other in utero growth restriction models.

Keywords: Adipose; Endocrine disruptor; Glucocorticoid; Gluconeogenesis; Glucose tolerance; Insulin sensitivity; Perinatal; Sex differences; Tolylfluanid.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adiposity / drug effects*
  • Animals
  • Endocrine Disruptors / toxicity*
  • Female
  • Insulin Resistance
  • Maternal Exposure / adverse effects*
  • Metabolic Diseases / chemically induced*
  • Metabolic Diseases / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Pregnancy
  • Prenatal Exposure Delayed Effects / chemically induced*
  • Prenatal Exposure Delayed Effects / metabolism
  • Receptors, Glucocorticoid / metabolism
  • Sex Characteristics
  • Sulfonamides / toxicity*
  • Toluidines / toxicity*

Substances

  • Endocrine Disruptors
  • Receptors, Glucocorticoid
  • Sulfonamides
  • Toluidines
  • N-dichlorofluoromethylthio-N',N'-dimethyl-N-p-tolylsulfamide