Elsevier

Placenta

Volume 34, Issue 12, December 2013, Pages 1128-1135
Placenta

Long-term type 1 diabetes impairs decidualization and extracellular matrix remodeling during early embryonic development in mice

On occasion of the 30th anniversary of the Laboratory of Reproductive and Extracellular Matrix Biology we dedicate this article to its founder, Professor Paulo Abrahamsohn.
https://doi.org/10.1016/j.placenta.2013.09.012Get rights and content
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Abstract

Introduction

Endometrial decidualization and associated extracellular matrix (ECM) remodeling are critical events to the establishment of the maternal–fetal interface and successful pregnancy. Here, we investigated the impact of type 1 diabetes on these processes during early embryonic development, in order to contribute to the understanding of the maternal factors associated to diabetic embryopathies.

Methods

Alloxan-induced diabetic Swiss female mice were bred after different periods of time to determine the effects of diabetes progression on the development of gestational complications. Furthermore, the analyses focused on decidual development as well as mRNA expression, protein deposition and ultrastructural organization of decidual ECM.

Results

Decreased number of implantation sites and decidual dimensions were observed in the group mated 90–110 days after diabetes induction (D), but not in the 50–70D group. Picrosirius staining showed augmentation in the fibrillar collagen network in the 90–110D group and, following immunohistochemical examination, that this was associated with increase in types I and V collagens and decrease in type III collagen and collagen-associated proteoglycans biglycan and lumican. qPCR, however, demonstrated that only type I collagen mRNA levels were increased in the diabetic group. Alterations in the molecular ratio among distinct collagen types and proteoglycans were associated with abnormal collagen fibrillogenesis, analyzed by transmission electron microscopy.

Conclusions

Our results support the concept that the development of pregnancy complications is directly related with duration of diabetes (progression of the disease), and that this is a consequence of both systemic factors (i.e. disturbed maternal endocrine–metabolic profile) and uterine factors, including impaired decidualization and ECM remodeling.

Keywords

Decidua
Extracellular matrix
Maternal–fetal interface
Mouse
Early embryonic development
Pregnancy
Type 1 diabetes

Abbreviations

D
days after diabetes induction
ECM
extracellular matrix
ELISA
enzyme-linked immunosorbent assay
GAPDH
glyceraldehyde-3-phosphate dehydrogenase
hp
hours of pregnancy
IL11
interleukin 11
MMP
matrix metalloproteinase
PBS
phosphate buffered saline
qPCR
quantitative real time PCR
SLRPs
small leucine rich proteoglycans

Cited by (0)

This study was conducted as partial fulfillment of the requirements for a PhD degree by Rodolfo Favaro (advisor, Telma Zorn). Fellowship (04/14442-6) and grants were provided by FAPESP (07/55277-6) and CNPq (306336/2006-5).