Abstract
IntroductionDespite tight glycemic control, pregnancy complication rate in type 1 diabetes patients is higher than in normal pregnancy. Other etiological factors may be responsible for the development of adverse pregnancy outcome. Acceptance of the semi-allogeneic fetus is accompanied by adaptations in the maternal immune-response. Maladaptations of the immune-response has been shown to contribute to pregnancy complications. We hypothesized that type 1 diabetes, as an autoimmune disease, may be associated with maladaptations of the immune-response to pregnancy, possibly resulting in pregnancy complications.MethodsWe studied pregnancy outcome and pregnancy-induced immunological adaptations in a normoglycemic rat-model of type 1 diabetes, i.e. biobreeding diabetes-prone rats (BBDP; 5 non-pregnant rats, 7 pregnant day 10 rats and 6 pregnant day 18 rats) , versus non-diabetic control rats (i.e. congenic non-diabetic biobreeding diabetes-resistant (BBDR; 6 non-pregnant rats, 6 pregnant day 10 rats and 6 pregnant day 18 rats) and Wistar-rats (6 non-pregnant, 6 pregnant day 10 rats and 5 pregnant day 18 rats)).ResultsWe observed reduced litter size, lower fetal weight of viable fetuses and increased numbers of resorptions versus control rats. These complications are accompanied by various differences in the immune-response between BBDP and control rats in both pregnant and non-pregnant animals. The immune-response in non-pregnant BBDP-rats was characterized by decreased percentages of lymphocytes, increased percentages of effector T-cells, regulatory T-cells and natural killer cells, an increased Th1/Th2-ratio and activated monocytes versus Wistar and BBDR-rats. Furthermore, pregnancy-induced adaptations in BBDP-rats coincided with an increased Th1/Th2-ratio, a decreased mean fluorescence intensity CD161a/NKR-P1b ratio and no further activation of monocytes versus non-diabetic control rats.ConclusionThis study suggests that even in the face of strict normoglycemia, pregnancy complications still occur in type 1 diabetic pregnancies. This adverse pregnancy outcome may be related to the aberrant immunological adaptations to pregnancy in diabetic rats.
Highlights
Despite tight glycemic control, pregnancy complication rate in type 1 diabetes patients is higher than in normal pregnancy
This study suggests that even in the face of strict normoglycemia, pregnancy complications still occur in type 1 diabetic pregnancies
This adverse pregnancy outcome may be related to the aberrant immunological adaptations to pregnancy in diabetic rats
Summary
Pregnancy complication rate in type 1 diabetes patients is higher than in normal pregnancy. Type 1 diabetes mellitus (T1D) during pregnancy is associated with adverse pregnancy outcome, such as pre-eclampsia, prematurity, macrosomia and perinatal death [1,2]. Up to now, this has been attributed to frequent episodes of hyperglycemia [3,4]. Macrophages infiltrate the decidua as well and differentiate towards the M2 phenotype, which have immunosuppressive properties [12,13] Altered adaptations in these immune-responses to pregnancy may induce maternal and perinatal complications, like pre-eclampsia, pregnancy-induced hypertension, intrauterine growth retardation, preterm delivery and/or abortion [14,15,16,17,18]. Disorders of the immune response at the peripheral level are linked to the development of (cardio)vascular diseases, such as hypertension [20]
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