Nifedipine Prevents Apoptosis of Alcohol‐Exposed First‐Trimester Trophoblast Cells. (22nd November 2017)

• Record Type: Journal Article
• Authors: Bolnick, Alan D.; Bolnick, Jay M.; Kohan‐Ghadr, Hamid‐Reza; Kilburn, Brian A.; Hertz, Michael; Dai, Jing; Drewlo, Sascha; Armant, D. Randall
• Is Part Of: Alcoholism. Volume 42:Number 1(2018)
• Page Start: 53
• Page End: 60
• Publication Date: 2017-11-22
• Subjects: Trophoblast -- Nifedipine -- Fetal Alcohol Spectrum Disorder -- Apoptosis -- Placenta; Alcoholism -- Periodicals; Alcoholism -- Periodicals; Alcoolisme; Electronic journals; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.861005
• DOI: 10.1111/acer.13534
• Languages: English
• ISSNs: 0145-6008

Abstract

Abstract : Background: Maternal alcohol abuse leading to fetal alcohol spectrum disorder (FASD) includes fetal growth restriction (FGR). Ethanol (EtOH) induces apoptosis of human placental trophoblast cells, possibly disrupting placentation and contributing to FGR in FASD. EtOH facilitates apoptosis in several embryonic tissues, including human trophoblasts, by raising intracellular Ca 2+ . We previously found that acute EtOH exposure increases trophoblast apoptosis due to signaling from both intracellular and extracellular Ca 2+ . Therefore, nifedipine, a Ca 2+ channel blocker that is commonly administered to treat preeclampsia and preterm labor, was evaluated for cytoprotective properties in trophoblast cells exposed to alcohol. Methods: Human first‐trimester chorionic villous explants and the human trophoblast cell line HTR‐8/SVneo (HTR) were pretreated with 12.5 to 50 nM of the Ca 2+ channel blocker nifedipine for 1 hour before exposure to 50 mM EtOH for an additional hour. Intracellular Ca 2+ concentrations were monitored in real time by epifluorescence microscopy, using fluo‐4‐AM. Apoptosis was assessed by t erminal deoxynucleotidyl transferase d U TP n ick e nd l abeling (TUNEL), accumulation of cytoplasmic cytochrome c, and cleavage rates of caspase 3 and caspase 9. Results: The increase in intracellular Ca 2+ upon exposure to EtOH in both villous explants and HTR cells was completely blocked ( p < 0.05) when pretreated with nifedipine, accompanied by inhibition of EtOH‐induced release of cytochrome c, caspase activities, and TUNEL. Conclusions: This study indicates that nifedipine can interrupt the apoptotic pathway downstream of EtOH exposure and could provide a novel strategy for future interventions in women with fetuses at risk for FASD.