Hyperglycemia induces embryopathy, even in the absence of systemic maternal diabetes: an in vivo test of the fuel mediated teratogenesis hypothesis

Michelle L Baack; Chunlin Wang; Shanming Hu; Jeffrey L Segar; Andrew W Norris

doi:10.1016/j.reprotox.2014.03.013

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Hyperglycemia induces embryopathy, even in the absence of systemic maternal diabetes: an in vivo test of the fuel mediated teratogenesis hypothesis

Journal article

Open access

Peer reviewed

Hyperglycemia induces embryopathy, even in the absence of systemic maternal diabetes: an in vivo test of the fuel mediated teratogenesis hypothesis

Michelle L Baack, Chunlin Wang, Shanming Hu, Jeffrey L Segar and Andrew W Norris

Reproductive toxicology (Elmsford, N.Y.), Vol.46, pp.129-136

07/2014

DOI: 10.1016/j.reprotox.2014.03.013

PMCID: PMC4067982

PMID: 24721120

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Abstract

Embryonic exposure to excess circulating fuels is proposed to underlie diabetic embryopathy. To isolate the effects of hyperglycemia from the many systemic anomalies of diabetes, we infused 4 mg/min glucose into the left uterine artery of non-diabetic pregnant rats on gestation days (GD) 7-9. Right-sided embryos and dams exhibited no glucose elevation. Embryos were assessed on GD13, comparing the left versus right uterine horns. Hyperglycemic exposure increased rates of embryopathy, resorptions, and worsened embryopathy severity. By contrast, saline infusion did not affect any of these parameters. To assess for possible embryopathy susceptibility bias between uterine horns, separate dams were given retinoic acid (25mg/kg, a mildly embryopathic dose) systemically on GD7.5. The resultant embryopathy rates were equivalent between uterine horns. We conclude that hyperglycemia, even in the absence of systemic maternal diabetes, is sufficient to produce in vivo embryopathy during organogenesis.

Fetal Diseases - etiology

Hyperglycemia - complications

Rats

Glucose - pharmacology

Rats, Sprague-Dawley

Organogenesis

Pregnancy

Teratogenesis

Animals

Diabetes Mellitus, Experimental

Fetal Diseases - pathology

Female

Pregnancy Outcome

Tretinoin - pharmacology

Details

Title: Subtitle: Hyperglycemia induces embryopathy, even in the absence of systemic maternal diabetes: an in vivo test of the fuel mediated teratogenesis hypothesis
Creators: Michelle L Baack - University of Iowa Children's Hospital, Department of Pediatrics, Iowa City, IA, USA
Chunlin Wang - University of Iowa Children's Hospital, Department of Pediatrics, Iowa City, IA, USA
Shanming Hu - University of Iowa Children's Hospital, Department of Pediatrics, Iowa City, IA, USA
Jeffrey L Segar - University of Iowa Children's Hospital, Department of Pediatrics, Iowa City, IA, USA
Andrew W Norris - University of Iowa Children's Hospital, Department of Pediatrics, Iowa City, IA, USA. Electronic address: andrew-norris@uiowa.edu
Resource Type: Journal article
Publication Details: Reproductive toxicology (Elmsford, N.Y.), Vol.46, pp.129-136
DOI: 10.1016/j.reprotox.2014.03.013
PMID: 24721120
PMCID: PMC4067982
NLM abbreviation: Reprod Toxicol
ISSN: 0890-6238
eISSN: 1873-1708
Publisher: United States
Grant note: R01 DK081548 / NIDDK NIH HHS R01 DK097820 / NIDDK NIH HHS K08 HL077344 / NHLBI NIH HHS T32 HL007344 / NHLBI NIH HHS T32 HL077344 / NHLBI NIH HHS K08 HD078504 / NICHD NIH HHS
Language: English
Date published: 07/2014
Academic Unit: Endocrinology and Diabetes; Stead Family Department of Pediatrics; Biochemistry and Molecular Biology
Record Identifier: 9984024510902771

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