The balance between human maternal plasma angiotensin II and angiotensin 1-7 levels in early gestation pregnancy is influenced by fetal sex

Abstract

Hypothesis: There are fetal sex-associated differences in the circulating maternal renin-angiotensin system (RAS) in early pregnancy. Methods: Plasma prorenin, angiotensin (Ang) II, Ang 1-7 and angiotensin-converting enzyme (ACE) concentrations were measured at 15 weeks' gestation in 131 women with uncomplicated pregnancies from the Adelaide SCOPE cohort. Uterine and umbilical artery Doppler sonography was performed at 20 weeks' gestation. Results: At 15 weeks, women bearing female fetuses had higher maternal Ang II concentrations (p = 0.017) and lower Ang 1-7 to Ang II ratios (p = 0.016) than women bearing males. In women with male fetuses, Ang II positively correlated with birth weight (p = 0.028) and prorenin negatively correlated with placental weight (p = 0.014). Female fetuses had higher umbilical artery resistance indices (p = 0.019) that were related to maternal prorenin concentrations (p = 0.007). Conclusions: In early human pregnancy, the maternal RAS is influenced by fetal sex. The lower Ang 1-7 to Ang II ratios in women with female fetuses may contribute to the lower maternal peripheral microvascular flow as described previously and the lack of any positive effect of Ang II on fetal growth, as seen in women with male fetuses.

Microvascular circulatory dysregulation driven in part by cystathionine gamma‐lyase: A new paradigm for cardiovascular compromise in the preterm newborn

“…Instead of postnatal vasoconstriction, peripheral dilation persists, driven by a number of mechanisms, one of which may be H 2 S. This hypothesis of persistent dilatory status following preterm birth is also supported by a growing body of work on the renin angiotensin system. Studies in a range of species, including humans, suggest that the balance of vasoactive renin angiotensin system peptides and their receptors favors vasodilatation during gestation and fetal life, particularly in males, and that this rapidly switches following birth—similar to the profile observed in the present study, with vasodilatation favored prenatally, and rapidly downregulated postnatally in term neonates. This, however, fails in preterm neonates who are unprepared for the extrauterine environment.…”

Sex differences in umbilical artery Doppler indices: a longitudinal study

“…However, it has been shown that male fetuses born at 24–28 weeks of gestation have more peripheral vasodilatation compared to female fetuses [ 44 ]. Furthermore, pregnant women carrying male fetuses are reported to have higher angiotensin (Ang) 1–7 to Ang II ratio in the second trimester [ 45 ]. As Ang II is a potent vasoconstrictor and Ang 1–7 is a known vasodilator, relative vasodilatation of placental vessels could be responsible for lower UA PI, RI, and S/D ratio observed in male fetuses.…”

Roles of the circulating renin-angiotensin-aldosterone system in human pregnancy

“…Of these peptides, ANG II and ANG (1-7) have been most studied in human pregnancy. At 15 wk gestation, ANG II levels are lower and the ANG (1-7)/ANG II ratio higher in women carrying male fetuses than in women carrying female fetuses (75). Baker et al (4) found that plasma ANG II levels were elevated by the second trimester.…”