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Hypoglycemia, hyperglucagonemia, and fetoplacental defects in glucagon receptor knockout mice: a role for glucagon action in pregnancy maintenance.
- Source :
-
American journal of physiology. Endocrinology and metabolism [Am J Physiol Endocrinol Metab] 2012 Mar 01; Vol. 302 (5), pp. E522-31. Date of Electronic Publication: 2011 Dec 13. - Publication Year :
- 2012
-
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.
- Subjects :
- Animals
Female
Fetal Death etiology
Fetal Diseases metabolism
Fetal Growth Retardation etiology
Gene Expression Regulation, Developmental
Glucagon blood
Heterozygote
Hypoglycemia metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Ovary drug effects
Ovary physiology
Pituitary Gland, Anterior metabolism
Pituitary Gland, Anterior pathology
Placenta metabolism
Placenta pathology
Placenta Diseases metabolism
Placenta Diseases pathology
Placentation
Pregnancy Proteins genetics
Pregnancy Proteins metabolism
Receptors, Glucagon genetics
Signal Transduction
Superovulation drug effects
Fetal Diseases etiology
Glucagon physiology
Hypoglycemia etiology
Placenta Diseases etiology
Pregnancy physiology
Receptors, Glucagon physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1555
- Volume :
- 302
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Endocrinology and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 22167521
- Full Text :
- https://doi.org/10.1152/ajpendo.00420.2011