Hypoglycemia, hyperglucagonemia, and fetoplacental defects in glucagon receptor knockout mice: A role for glucagon action in pregnancy maintenance

Sophia Ouhilal, Patricia Vuguin, Lingguang Cui, Xiu Quan Du, Richard W. Gelling, Sandra E. Reznik, Robert Russell, Albert F. Parlow, Clara Karpovsky, Nanette Santoro, Maureen J. Charron

Research output: Contribution to journalArticle

14 Scopus citations


Alterations in insulin signaling as well as insulin action predispose to infertility as well as adverse pregnancy outcomes; however, little is known about the role of glucagon signaling in reproduction. The glucagon receptor knockout (Gcgr -/-) mouse created by our laboratory was used to define the role of glucagon signaling in maintaining normal reproduction. In this mouse model, lack of glucagon signaling did not alter the hypothalamic- pituitary-ovarian axis. Pregnant Gcgr -/- female mice displayed persistent hypoglycemia and hyperglucagonemia. Gcgr -/- pregnancies were associated with decreased fetal weight, increased late-gestation fetal demise, and significant abnormalities of placentation. Gcgr -/- placentas contained areas of extensive mineralization, fibrinoid necrosis, narrowing of the vascular channels, and a thickened interstitium associated with trophoblast hyperplasia. Absent glucagon signaling did not alter glycogen content in Gcgr -/- placentas but significantly downregulated genes that control growth, adrenergic signaling, vascularization, oxidative stress, and G protein-coupled receptors. Our data suggest that, similarly to insulin, glucagon action contributes to normal female reproductive function.

Original languageEnglish (US)
Pages (from-to)E522-E531
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number5
StatePublished - Mar 1 2012



  • Fetal growth
  • Placenta

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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