Fetal sex and maternal fasting glucose affect neonatal cord blood-derived endothelial progenitor cells

BACKGROUND: Maternal cardiovascular risk factors (CVRF) in pregnancy, i.e., obesity and hyperglycemia, transmit to the fetus and affect placental and fetal endothelial function. Moreover, a sex dimorphism in endothelial function and susceptibility towards CVRF exists already in utero. Endothelial colony-forming cells (ECFC) are circulating endothelial progenitors highly present in neonatal cord blood and sensitive to CVRF. This study investigated whether fetal sex or subtle maternal metabolic changes within healthy range alter fetal ECFC outgrowth. METHODS; Outgrowth of ECFC from cord blood of male (n = 31) and female (n = 26) neonates was analyzed after healthy pregnancies and related to fetal sex and maternal metabolic parameters. RESULTS: Male ECFC grew out earlier (-20.57% days; p = 0.031) than female. Although all women were non-diabetic, higher levels of fasting plasma glucose (FPG) at midpregnancy increased the time required for colony outgrowth (OR: 1.019; p = 0.030), which, after stratifying for fetal sex, was significant only in the males. Gestational weight gain and BMI did not affect outgrowth. Colony number was unchanged by all parameters. CONCLUSIONS: Fetal sex and maternal FPG within normal range alter ECFC function in utero. A role of ECFC in postnatal angiogenesis and vasculogenesis has been suggested, which may be affected by altered outgrowth dynamics. Impact This study is the first to report that a sexual dimorphism exists in ECFC function, as cells of female progeny require a longer period of time until colony outgrowth than ECFC of male progeny. Our data show that ECFC function is highly sensitive and affected by maternal glucose levels even in a normal, non-diabetic range. Our data raise the question of whether maternal plasma glucose in pregnancy should be considered to play a critical role even in the non-diabetic setting.

Automated summary

The study found that there is a sexual dimorphism in the function of endothelial colony-forming cells (ECFC), with female progeny cells requiring a longer period of time for colony outgrowth compared to male progeny cells. Additionally, even within a normal, non-diabetic range, maternal glucose levels can significantly affect ECFC function in utero.