TY - JOUR
T1 - Hypoglycemia, hyperglucagonemia, and fetoplacental defects in glucagon receptor knockout mice
T2 - A role for glucagon action in pregnancy maintenance
AU - Ouhilal, Sophia
AU - Vuguin, Patricia
AU - Cui, Lingguang
AU - Du, Xiu Quan
AU - Gelling, Richard W.
AU - Reznik, Sandra E.
AU - Russell, Robert
AU - Parlow, Albert F.
AU - Karpovsky, Clara
AU - Santoro, Nanette
AU - Charron, Maureen J.
PY - 2012/3
Y1 - 2012/3
N2 - 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.
AB - 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.
KW - Fetal growth
KW - Placenta
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U2 - 10.1152/ajpendo.00420.2011
DO - 10.1152/ajpendo.00420.2011
M3 - Article
C2 - 22167521
AN - SCOPUS:84857280811
SN - 0193-1849
VL - 302
SP - E522-E531
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
IS - 5
ER -