Maternal diabetes impairs gastrulation and insulin and IGF-I receptor expression in rabbit blastocysts.

Abstract:

:Women with type 1 diabetes are subfertile. Diabetes negatively affects pregnancy by causing early miscarriage and poor prenatal outcomes. In this study we examine consequences of maternal type 1 diabetes on early embryo development, metabolic gene expression, and the pattern of insulin receptor (IR) and IGF-I receptor (IGF-IR) distribution in rabbit blastocysts. In female rabbits, type 1 diabetes was induced by alloxan treatment. Six-day-old blastocysts were recovered and assessed for receptor distribution and metabolic gene expression. In vitro culture of blastocysts was performed in medium containing 1 mm, 10 mm, or 25 mm glucose, simulating normo- and hyperglycemic developmental condition in vitro. The fertility rate of the diabetic rabbits clearly mirrored subfertility with a drop in blastocyst numbers by 40% (13.3 blastocysts in diabetic vs. 21.9 in control females). In blastocysts onset and progression of gastrulation was delayed and expression of IR and IGF-IR and their metabolic target genes (hexokinase, phosphoenolpyruvate carboxykinase), both in vivo and in vitro, was down-regulated. The amount of apoptotic cells in the embryonic disc was increased, correlating closely with the reduced transcription of the bcl-x(L) gene. Blastocyst development is clearly impaired by type 1 diabetes during early pregnancy. Insulin-stimulated metabolic genes and IR and IGF-IR are down-regulated, resulting in reduced insulin and IGF sensitivity and a delay in development. Dysregulation of the IGF system and embryonic glucose metabolism are potential reasons for diabetogenous subfertility and embryopathies and start as soon as during the first days of life.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Ramin N,Thieme R,Fischer S,Schindler M,Schmidt T,Fischer B,Navarrete Santos A

doi

10.1210/en.2010-0187

subject

Has Abstract

pub_date

2010-09-01 00:00:00

pages

4158-67

issue

9

eissn

0013-7227

issn

1945-7170

pii

en.2010-0187

journal_volume

151

pub_type

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