Women with type 1 and 2 diabetes mellitus (DM) have increased risk of adverse perinatal outcomes, including carrying a fetus with congenital malformation, intrauterine fetal demise, intrauterine growth restriction, macrosomia, and postnatal metabolic disturbances. Early glycemic control in pregnancy is crucial for decreasing adverse outcomes. However, it is unclear whether preconception hyperglycemia also contributes to adverse perinatal outcomes in diabetes. We examined preconception versus intrauterine effects of hyperglycemia on perinatal outcomes using a mouse model of reciprocal embryo transfer, in which embryos produced with oocytes from diabetic (DMOD) or non-diabetic (COD) oocyte donors are transferred to diabetic (DMS) or non-diabetic (CS) surrogate mothers.
Diabetes was induced by intraperitoneal injection of streptozotocin 200mg/kg into 5 weeks old CD-1 mice. Upon reaching sexual maturity diabetic and control females were used as oocyte donors for in vitro fertilization (IVF) and as surrogate mothers for embryo transfer. Caesarian section was performed at term. One-way ANOVA was used to compare embryo ability to develop (implantation, fetal and abortion rates), fetal and placental weights, and incidence of congenital anomalies.
The diabetic and non-diabetic surrogate mothers had similar ability to carry pregnancy, evidenced as rate of live fetuses (%, DMOD-DMS: 49 ± 7; COD-DMS: 51± 9; DMOD-CS: 66 ± 6; COD-CS: 60 ± 8; P=0.43). Implantation and abortion rates also did not differ among the four groups (P=0.81 and P=0.14). Fetal weights were significantly decreased in offspring from diabetic surrogate mothers, (g, DMOD-DMS: 0.9 ± 0.03; COD-DMS: 0.77± 0.04; DMOD- CS: 1.37 ± 0.02; COD-CS: 1.35 ± 0.02; P=0.0012) while placental weights were similar (P=0.43). Fetuses with major congenital anomalies (anencephaly, myelomenigocele, abdominal wall defect) were observed only with diabetic surrogate mothers (%, DMOD-DMS: 15 ± 6; COD-DMS: 35 ± 15; P=0.003).
Diabetic status does not interfere with ability to carry pregnancy. However, adverse perinatal outcomes result when pregnancy is carried by diabetic surrogate mothers regardless whether oocytes are from diabetic or non-diabetic donor. This suggests that pregnancy environment is causative of adverse perinatal outcomes associated with diabetes, which underlines the importance of glycemic control in pregnancy.
© 2018 Published by Elsevier Inc.