Mineralocorticoid effects in the late gestation ovine fetal lung

Abstract

This study was designed to determine the effects of corticosteroids at MR in the late‐gestation fetal lung. Since both the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR) are expressed at relatively high levels in the fetal lung, endogenous corticosteroids may act at MR as well as GR in the preterm fetal lung. The GR agonist, betamethasone, the MR agonist, aldosterone, or both were infused intravenously for 48 h in ovine fetuses of approximately 130 days gestation. Effects on airway pressures during stepwise inflation of the in situ lung, expression of ENaC alpha (SCNN1A), ENaC beta (SCNN1B), and Na,K ATPase (ATP1A1), and elastin and collagen content were determined after the infusions. We found that aldosterone significantly reduced the airway pressure measured during the initial step in inflation of the lung, although aldosterone had no overall effect on lung compliance, nor did aldosterone induce expression of ENaCα, ENaCβ or Na,K ATPaseα1. Betamethasone significantly increased expression of the epithelial sodium channel (ENaC) subunit mRNAs, and collagen and elastin content in the lungs, although this dose of betamethasone also had no effect on lung compliance. There was no synergy between effects of the MR and GR agonists. Transcriptomic analysis suggested that although aldosterone did not alter genes in pathways related to epithelial sodium transport, aldosterone did alter genes in pathways involved in cell proliferation in the lungs. The results are consistent with corticosteroid‐induced fluid reabsorption at birth through GR rather than MR, but suggest that MR facilitates lung maturation, and may contribute to inflation with the first breaths via mechanisms distinct from known aldosterone effects in other epithelia.

Early pregnancy maternal progesterone administration alters pituitary and testis function and steroid profile in male fetuses

“…It is not known what effects mineralocorticoids have in the fetus. They may have roles alongside glucocorticoids in lung development 38 and the programming of future hypertension 39 in animal models. It has been postulated that progesterone metabolism through corticosterone to mineralocorticoids is involved in programming autism 40 , 41 .…”

Birth delivery method affects expression of immune genes in lung and jejunum tissue of neonatal beef calves

“…Without the onset of labour, the initiation of this surfactant secretion does not occur, meaning that the overall concentration does not reach the necessary levels needed for rapid transition at birth [ 11 ]. ECS deliveries before the prepartum increase of hormones also results in a reduction in the expression of additional proteins such as antioxidants and does not occur at its peak and necessary level [ 30 ]. This was highlighted in our study, as we showed an almost four fold reduction to the relative abundance of CYP1A1 .…”

The role of serum-glucocorticoid regulated kinase 1 in reproductive viability: implications from prenatal programming and senescence

“…The induction of SGK1 increases distal lung fluid absorption by activating α subnet of epithelial Na + channel (α-ENaC) [ 82 ] through Nedd4-2 suppression in fetal lung tissue [ 83 ]. By the same token, SGK1 in placental trophoblast contributes to normal sodium homeostasis in the bidirectional process of maternal–fetal fluid exchange by modulating trophoblast Na + transport under the stimulation of corticosteroids [ 84 ]. Besides, two single-nucleotide polymorphisms (SNPs) of SGK1 (rs1057293 and rs1743966) were reported to be related to transient tachypnea of the newborn (TTN) [ 85 ], proposing a protecting role in fetal growth and development [ 86 ].…”