Abstract
IntroductionThe birth of most mammals features a dramatic increase in oxygen while placenta‐derived hormones such as β‐estradiol and progesterone plummet. In experimental newborn animals, transiently elevated oxygen concentrations cause death of neurons, astrocytes, and oligodendrocyte precursors. High oxygen has been associated with cerebral palsy in human preterm infants while progesterone is being used to prevent preterm delivery and investigated as a neuroprotective agent.MethodsIn this study, we investigated the effects of hyperoxia (80% O2 for 24, 48, and 72 h) on cultured C8‐D1A astrocytes in the presence or absence of progesterone at concentrations ranging from 10−9 to 10−5 mol/L.ResultsHyperoxia measured by methytetrazolium assay (MTT) reduced cell viability, increased release of lactate dehydrogenase (LDH), reduced carboxyfluorescein diacetate succinimidyl ester (CFSE)‐assessed cell proliferation, and downregulated Cylin D2 expression. Progesterone did not affect any of these hyperoxia‐mediated indicators of cell death or malfunctioning. Real‐time PCR analysis showed that hyperoxia caused downregulation of the progesterone receptors PR‐AB und PR‐B.ConclusionsOur experiments showed that there was no protective effect of progesterone on hyperoxia‐inducted cell damage on mouse C8‐D1A astrocytes. Down regulation of the progesterone receptors might be linked to the lack of protective effects.
Highlights
The birth of most mammals features a dramatic increase in oxygen while placenta-derived hormones such as b-estradiol and progesterone plummet
Cell Death Detection ELISA revealed a significant rise of released mono- and oligonucleosomes in the cytoplasm of hyperoxia-treated cells compared to cells in normoxia (1.16 vs. 0.94; P < 0.05) (Fig. 2A)
In contrast to our initial hypothesis, experiments of this study showed that treatment with progesterone does not
Summary
The birth of most mammals features a dramatic increase in oxygen while placenta-derived hormones such as b-estradiol and progesterone plummet. After delivery of a premature infant, this placental supply is disrupted, resulting in a rapid decrease in both 17b-estradiol and progesterone. Replacement of these placental hormones aiming at intrauterine conditions has been hypothesized to be beneficial. In extremely low birth weight infants who had been randomized to receive or not to receive postnatal replacement of 17b-estradiol and progesterone, neurodevelopmental follow-up at 5 years corrected age suggested a significant time–response relationship between hormone replacement and cerebral palsy, with every day of treatment significantly reducing the risk for cerebral palsy (Trotter et al 2012)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
