Abstract
BackgroundPlasma and urine levels of the potent vasodilator Ang-(1–7) are elevated in mid and late pregnancy and are correlated with elevated placental angiogenesis, fetal blood flow, and rapid fetal growth. We hypothesized that Ang-(1–7), its receptor (Mas1) and the enzymes involved in Ang-(1–7) production (ACE2 and Membrane metallo-endopeptidase; MME) are down regulated in response to glucocorticoid administration contributing to IUGR.MethodsPregnant female Sprague–Dawley rats were injected with dexamethasone (DEX; 0.4 mg/kg/day) starting from 14 day gestation (dg) till sacrifice at 19 or 21 dg while control groups were injected with saline (n = 6/group). The gene and protein expression of ACE2, MME, Ang-(1–7) and Mas1 receptor in the placental labyrinth (LZ) and basal zones (BZ) were studied. ResultsDEX administration caused a reduction in LZ weight at 19 and 21 dg (p < 0.001). IUGR, as shown by decreased fetal weights, was evident in DEX treated rats at 21 dg (p < 0.01). ACE2 gene expression was elevated in the LZ of control placentas at 21 dg (p < 0.01) compared to 19 dg and DEX prevented this rise at both gene (p < 0.01) and protein levels (p < 0.05). In addition, Ang-(1–7) protein expression in LZ was significantly reduced in DEX treated rats at 21 dg (p < 0.05). On the other hand, Mas1 and MME were upregulated in LZ at 21 dg in both groups (p < 0.05 and p < 0.001, respectively).ConclusionThe results of this study indicate that a reduced expression of ACE2 and Ang-(1–7) in the placenta by DEX treatment may be responsible for IUGR and consequent disease programming later in life.
Highlights
Plasma and urine levels of the potent vasodilator Ang-(1–7) are elevated in mid and late pregnancy and are correlated with elevated placental angiogenesis, fetal blood flow, and rapid fetal growth
Effect of dexamethasone on the gene expression of Angiotensin Iconverting enzyme 2 (ACE2), Mas1, and Membrane Metallo-Endopeptidase (MME) in basal and labyrinth zones In the basal zone, the mRNA levels of ACE2 and Mas1 were significantly higher within the control groups at 21
This study shows that maternal dexamethasone treatment leads to intrauterine growth restriction (IUGR) and reduces the levels of ACE2 and Ang-(1–7) in the rat labyrinth zone in late pregnancy
Summary
Plasma and urine levels of the potent vasodilator Ang-(1–7) are elevated in mid and late pregnancy and are correlated with elevated placental angiogenesis, fetal blood flow, and rapid fetal growth. Administration of glucocorticoids (Betamethasone and/ or Dexamethasone) to pregnant women endangered by premature labor is a standard clinical procedure beneficial in terms of maturation of fetal lungs and prevention of serious fetal respiratory problems [1,2,3,4]. The basal zone is the site of placental hormone production during mid to late pregnancy [11] with both trophoblast and maternal vessels, but no fetal vessels [12]. The labyrinth zone is close to the fetal side and includes trophoblast cells as well as maternal and fetal vessels. It is the main area involved in maternal-fetal hemotrophic exchange of nutrients and waste-products
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