Abstract
Oxygen causes white matter damage in preterm infants and male sex is a major risk factor for poor neurological outcome, which speculates the role of steroid hormones in sex-based differences. Preterm birth is accompanied by a drop in 17β-estradiol (E2) and progesterone along with increased levels of fetal zone steroids (FZS). We performed a sex-based analysis on the FZS concentration differences in urine samples collected from preterm and term infants. We show that, in preterm urine samples, the total concentration of FZS, and in particular the 16α-OH-DHEA concentration, is significantly higher in ill female infants as compared to males. Since we previously identified Nup133 as a novel target protein affected by hyperoxia, here we studied the effect of FZS, allopregnanolone (Allo) and E2 on differentiation and Nup133 signaling using mouse-derived primary oligodendrocyte progenitor cells (OPCs). We show that the steroids could reverse the effect of hyperoxia-mediated downregulation of Nup133 in cultured male OPCs. The addition of FZS and E2 protected cells from oxidative stress. However, E2, in presence of 16α-OH-DHEA, showed a negative effect on male cells. These results assert the importance of sex-based differences and their potential implications in preterm stress response.
Highlights
Preterm birth is one of the leading causes of neonatal morbidity and mortality [1,2].These babies are at a high risk of severe developmental disabilities as prematurity is associated with complex adverse consequences
In our previous study we evaluated the receptors involved in the protective effect observed by FZS and found that the neuroprotection by FZSs was highly dependent on the cell type-specific expression of aromatases, the receptor repertoire and the potency of the fetal zone steroids towards these receptors [21]
The brain is left extremely vulnerable as it is deprived of Following preterm birth, the brain is left extremely vulnerable as it is deprived of essential supplies from the placenta including steroids, enzymes and nutrients and at the essential supplies from theisplacenta including steroids, enzymes and nutrients and at as thehyperoxia and same time prematurely exposed to stimulating environments such same time is prematurely exposed to stimulating environments such as hyperoxia and associated damage [29]
Summary
Preterm birth is one of the leading causes of neonatal morbidity and mortality [1,2]. There is accumulating evidence that females have an advantage over males with a better outcome in the perinatal period, after preterm birth [4] This gender-based difference points towards a possible role of hormones and, considering its relation to hyperoxia, it becomes important to identify the underlying reasons for differential responses. At the time of birth, after the umbilical cord is clamped, E2 level decreases by a factor of 100 within 24 h [13] In humans, this estrogen synthesis by the placenta during pregnancy is largely dependent on androgens from the fetal and maternal adrenal glands. We FZS, Allo project possible role but at the same time, a differential effect on the maturation of male and female derived planation for the differences in urinary steroid profiles observed in preterm infants and primary OPCs. Based on the results, we project a possible explanation for the differences their potential implications. In urinary steroid profiles observed in preterm infants and their potential implications
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