Aberrant endometrial features of pregnancy in diabetic NOD mice.
OBJECTIVE
Pregnant diabetic women are at a 4-12 times higher risk for preeclampsia, an urgent acute-onset complication of mid- to late gestation, than normal pregnant women. Hallmarks of preeclampsia are hypertension, proteinuria, and incomplete modification of endometrial spiral arteries. Transient proangiogenic lymphocytes called uterine natural killer (uNK) cells are implicated in human and rodent spiral artery modification. We studied mid- to late gestations in spontaneously type 1 diabetic NOD mice to investigate whether diabetes alters uNK cell homing and/or function.


METHODS
Normoglycemic, pre-diabetic, and diabetic NOD mice and controls were mated. Lymphocytes and endometrial endothelium and decidua were studied histologically and in functional assays.


RESULTS
Conception accelerated progression to overt diabetes in NOD females who had limited spiral artery development, heavier placentas, and lighter fetuses displaying numerous birth defects compared with controls. UNK cell numbers were reduced in the decidua basalis of diabetic females, whereas interferon-gamma production was elevated. In diabetic NOD mice, decidual expression of the mucosal vascular addressin cell adhesion molecule (MAdCAM)-1 was aberrant in position, whereas vascular cell adhesion molecule (VCAM)-1 expression was reduced. Assays of lymphocyte adhesion to tissue sections under shear forces indicated that diabetes compromises the potential homing functions of both endometrial endothelium and peripheral NK cells.


CONCLUSIONS
In diabetes, gestational endometrium has immune and vascular defects that likely contribute to murine fetal loss and birth defects. Analogous problems and preeclampsia in diabetic women may involve similar mechanisms.
Burke
Suzanne D
SD
Department of Anatomy and Cell Biology, Queen's University, Kingston, Ontario, Canada. 5sb28@queensu.ca
Dong
Hongmei
H
Hazan
Aleah D
AD
Croy
B Anne
BA
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications*; D004195:Disease Models, Animal; D010064:Embryo Implantation; D004717:Endometrium / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011225:Pre-Eclampsia / Q000473:pathology; D011236:Prediabetic State / Q000150:complications / Q000473:pathology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000473:pathology*