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

12 Citations (Scopus)

Abstract

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)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume302
Issue number5
DOIs
StatePublished - Mar 2012
Externally publishedYes

Fingerprint

Glucagon Receptors
Pregnancy Maintenance
Glucagon
Hypoglycemia
Knockout Mice
Insulin
Placenta
Reproduction
Placentation
Pregnancy
Fetal Weight
Fetal Death
Trophoblasts
Pregnancy Outcome
G-Protein-Coupled Receptors
Heat-Shock Proteins
Glycogen
Adrenergic Agents
Infertility
Hyperplasia

Keywords

  • Fetal growth
  • Placenta

ASJC Scopus subject areas

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

Cite this

Hypoglycemia, hyperglucagonemia, and fetoplacental defects in glucagon receptor knockout mice : A role for glucagon action in pregnancy maintenance. / Ouhilal, Sophia; Vuguin, Patricia; Cui, Lingguang; Du, Xiu Quan; Gelling, Richard W.; Reznik, Sandra E.; Russell, Robert; Parlow, Albert F.; Karpovsky, Clara; Santoro, Nanette; Charron, Maureen J.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 302, No. 5, 03.2012.

Research output: Contribution to journalArticle

Ouhilal, Sophia ; Vuguin, Patricia ; Cui, Lingguang ; Du, Xiu Quan ; Gelling, Richard W. ; Reznik, Sandra E. ; Russell, Robert ; Parlow, Albert F. ; Karpovsky, Clara ; Santoro, Nanette ; Charron, Maureen J. / Hypoglycemia, hyperglucagonemia, and fetoplacental defects in glucagon receptor knockout mice : A role for glucagon action in pregnancy maintenance. In: American Journal of Physiology - Endocrinology and Metabolism. 2012 ; Vol. 302, No. 5.
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