Y It Matters—Sex Differences in Fetal Lung Development

Abstract

Within this review, sex-specific differences in alveolar epithelial functions are discussed with special focus on preterm infants and the respiratory disorders associated with premature birth. First, a short overview about fetal lung development, the challenges the lung faces during perinatal lung transition to air breathing and respiratory distress in preterm infants is given. Next, clinical observations concerning sex-specific differences in pulmonary morbidity of human preterm infants are noted. The second part discusses potential sex-specific causes of pulmonary complications, including pulmonary steroid receptors and local lung steroid metabolism. With regard to pulmonary steroid metabolism, it is important to highlight which steroidogenic enzymes are expressed at which stage during fetal lung development. Thereafter, we review the knowledge concerning sex-specific aspects of lung growth and maturation. Special focus is given to alveolar epithelial Na+ transport as a driver of perinatal lung transition and the sex differences that were noted in this process.

The association between sex and neonatal respiratory distress syndrome

“…The mechanism via which sex influences the risk of NRDS is unknown, and there are two probable explanations: (1) Male fetuses are significantly more likely than female fetuses to be born prematurely, and their average GA is significantly lower than that of their female counterparts. Additionally, there is a negative correlation between the incidence of NRDS and gestational age [ 12 ]; and (2) there may be a connection between sex hormone action during lung development [ 13 ]. Androgens include dehydroepiandrosterone, androstenedione and testosterone, and the main androgen in male is testosterone, which is produced by testicular mesenchymal cells and released into the circulatory system.…”

The association between sex and neonatal respiratory distress syndrome

“…The mechanism via which sex in uences the risk of NRDS is unknown, and there are two probable explanations: (1) Male fetuses are signi cantly more likely than female fetuses to be born prematurely, and their average gestational age is signi cantly lower than that of their female counterparts. Additionally, there is a negative correlation between the incidence of NRDS and gestational age [11]; and (2) there may be a connection between sex hormone action during lung development [12]. Androgens include dehydroepiandrosterone, androstenedione and testosterone, and the main androgen in men is testosterone, which is produced by testicular mesenchymal cells and released into the circulatory system.…”

Morbidity and Mortality of Very-Low-Birthweight Twin Infants according to Their Sex and the Sex of the Co-Twin: A Retrospective Cohort Study

“…On the other hand, males exposed to higher levels of oestrogens, as could be in the case of a female co-twin, could benefit from a better alveolar development and from the development of epithelial sodium channels, which are important for the absorption of foetal lung fluid after birth [22]. In summary, the functional development and maturation of the lung is a complex biochemical process influenced by a variety of hormones such as glucocorticoids, sex steroids, prolactin, insulin, catecholamines, and several growth factors [23]. In addition, the existence of differences by sex in terms of morbidity in other organs and systems, such as cardiovascular, neurological, digestive, etc., suggests that other mechanisms beyond pulmonary maturation could be involved [24].…”