Prenatal Testosterone Programming of Insulin Resistance in the Female Sheep

Adv Exp Med Biol. 2017;1043:575-596. doi: 10.1007/978-3-319-70178-3_25.


Insulin resistance, a common feature of metabolic disorders such as obesity, nonalcoholic fatty liver disease, metabolic syndrome, and polycystic ovary syndrome, is a risk factor for development of diabetes. Because sex hormones orchestrate the establishment of sex-specific behavioral, reproductive, and metabolic differences, a role for them in the developmental origin of insulin resistance is also to be expected. Female sheep exposed to male levels of testosterone during fetal life serve as an excellent translational model for delineating programming of insulin resistance. This chapter summarizes the ontogeny of insulin resistance, the tissue-specific changes in insulin sensitivity, and the various factors that are involved in the programming and maintenance of the insulin resistance in adult female sheep that were developmentally exposed to fetal male levels of testosterone during the sexual-differentiation window.

Keywords: Adiponectin; Developmental Programming; Inflammation; Insulin Resistance; Lipotoxicity; Oxidative Stress; Sheep; Testosterone.

Publication types

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

MeSH terms

  • Animals
  • Biomarkers / blood
  • Blood Glucose / metabolism
  • Disease Models, Animal
  • Female
  • Gestational Age
  • Insulin / blood*
  • Insulin Resistance*
  • Male
  • Maternal Exposure*
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Sex Determination Processes
  • Sex Differentiation
  • Sex Factors
  • Sheep, Domestic
  • Testosterone*


  • Biomarkers
  • Blood Glucose
  • Insulin
  • Testosterone