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Male Sex is Associated with a Reduced Alveolar Epithelial Sodium Transport

Till Kaltofen1, Melanie Haase1, Ulrich H Thome1

  • 1Center for Pediatric Research Leipzig, Division of Neonatology, Hospital for Children & Adolescents, University of Leipzig, Leipzig, Germany.

Plos One
|August 21, 2015
PubMed

Insights

Female preterm infants have a lower risk of respiratory distress syndrome (RDS) due to enhanced alveolar sodium transport. This is linked to higher expression of hormone receptors and sodium transporters in female lung cells.

Area of Science:

  • Neonatal Physiology
  • Pulmonary Medicine
  • Endocrinology

Background:

  • Respiratory distress syndrome (RDS) is a common complication in preterm infants, with a higher incidence in males ('male disadvantage').
  • Alveolar fluid clearance, driven by sodium (Na+) transport via epithelial Na+ channels (ENaC) and Na,K-ATPase, is critical for preventing RDS.
  • Potential sex-based differences in Na+ transporter expression or activity may explain the observed gender imbalance in RDS.

Purpose of the Study:

  • To investigate sex-based differences in Na+ transport and its underlying mechanisms in fetal distal lung epithelial (FDLE) cells.
  • To determine if differences in ENaC and Na,K-ATPase expression or activity contribute to the male disadvantage in RDS.

Main Methods:

  • Sex separation and analysis of rat fetal distal lung epithelial (FDLE) cells.
  • Ussing chamber experiments to measure short-circuit current (ISC) and amiloride- or ouabain-sensitive currents.
  • Quantitative analysis of FDLE cell yield and lung wet-to-dry weight ratio.
  • Measurement of mRNA levels for ENaC, Na,K-ATPase, estrogen receptors (ER), and progesterone receptors (PR).

Main Results:

  • Female FDLE cells exhibited higher baseline and maximal amiloride-sensitive ISC, indicating greater Na+ transport capacity.
  • Maximal ouabain-sensitive ISC was also higher in female cells, suggesting enhanced Na,K-ATPase activity.
  • Female fetuses yielded more FDLE cells and had lower lung wet-to-dry weight ratios.
  • Female FDLE cells showed higher mRNA expression for ENaC, Na,K-ATPase, ER, and PR.
  • Inhibition of ER-β abolished sex differences; female cells responded more to estradiol.

Conclusions:

  • Female fetal lung epithelial cells possess a higher capacity for Na+ transport, mediated by ENaC and Na,K-ATPase.
  • Increased expression of hormone receptors (ER, PR) in female FDLE cells may enhance responsiveness to estradiol, contributing to higher Na+ transport.
  • These sex-specific differences in alveolar Na+ transport offer a physiological explanation for the lower incidence and better outcome of RDS in female infants.

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