Elevated maternal cortisol leads to relative maternal hyperglycemia and increased stillbirth in ovine pregnancy

Am J Physiol Regul Integr Comp Physiol. 2014 Aug 15;307(4):R405-13. doi: 10.1152/ajpregu.00530.2013. Epub 2014 Jun 11.

Abstract

In normal pregnancy, cortisol increases; however, further pathological increases in cortisol are associated with maternal and fetal morbidities. These experiments were designed to test the hypothesis that increased maternal cortisol would increase maternal glucose concentrations, suppress fetal growth, and impair neonatal glucose homeostasis. Ewes were infused with cortisol (1 mg·kg(-1)·day(-1)) from day 115 of gestation to term; maternal glucose, insulin, ovine placental lactogen, estrone, progesterone, nonesterified free fatty acids (NEFA), β-hydroxybutyrate (BHB), and electrolytes were measured. Infusion of cortisol increased maternal glucose concentration and slowed the glucose disappearance after injection of glucose; maternal infusion of cortisol also increased the incidence of fetal death at or near parturition. The design of the study was altered to terminate the study prior to delivery, and post hoc analysis of the data was performed to test the hypothesis that maternal metabolic factors predict the fetal outcome. In cortisol-infused ewes that had stillborn lambs, plasma insulin was increased relative to control ewes or cortisol-infused ewes with live lambs. Maternal cortisol infusion did not alter maternal food intake or plasma NEFA, BHB, estrone, progesterone or placental lactogen concentrations, and it did not alter fetal body weight, ponderal index, or fetal organ weights. Our study suggests that the adverse effect of elevated maternal cortisol on pregnancy outcome may be related to the effects of cortisol on maternal glucose homeostasis, and that chronic maternal stress or adrenal hypersecretion of cortisol may create fetal pathophysiology paralleling some aspects of maternal gestational diabetes.

Keywords: cortisol; glucose; insulin; pregnancy.

Publication types

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

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Cushing Syndrome / blood
  • Cushing Syndrome / chemically induced*
  • Cushing Syndrome / complications
  • Diabetes, Gestational / blood
  • Diabetes, Gestational / etiology*
  • Disease Models, Animal
  • Energy Metabolism
  • Female
  • Fetal Blood / metabolism
  • Fetal Death / blood
  • Fetal Death / etiology*
  • Gestational Age
  • Homeostasis
  • Hydrocortisone* / administration & dosage
  • Hyperglycemia / blood
  • Hyperglycemia / etiology*
  • Infusions, Intravenous
  • Insulin / blood
  • Maternal Exposure*
  • Placenta / metabolism
  • Pregnancy
  • Sheep
  • Stillbirth*
  • Time Factors

Substances

  • Blood Glucose
  • Insulin
  • Hydrocortisone