Induction of the apoptotic pathway by oxidative stress in spontaneous preterm birth: Single nucleotide polymorphisms, maternal lifestyle factors and health status

Abstract

Abstract. The purpose of the present study was to search for associations between spontaneous preterm birth (sPTB), single nucleotide polymorphisms (SNPs) associated with the apoptotic pathway as triggered by oxidative stress, maternal lifestyle and health status. SNP genotyping [rs7560 for c-Jun N-terminal kinase (JNK), rs9517320 for mammalian STE20-like protein kinase 3 (MST3), rs1049216 for caspase 3 (CASP3)] in the placenta and maternal blood of 300 controls with at-term birth and 43 cases of sPTB was performed. No association was identified in genotype frequencies or combinations of foetal/maternal genotypes between single SNPs and sPTB. The risk of sPTB was significantly reduced by physical activity and significantly increased by current hypertensive diseases, premature rupture of membranes (PROM) or preterm PROM (P-PROM) and previous sPTB. The TT/GA genotype of JNK/CASP3 in maternal blood and maternal health status (current hypertensive diseases, current PROM/ P-PROM, previous sPTB) were independently associated with sPTB. The present findings suggested that, independently of other maternal factors, pregnant women carrying the TT/GA genotype of JNK/CASP3 were more susceptible to sPTB than women bearing the GT/GA (our reference) genotype; that the apoptotic pathway triggered by oxidative stress was involved; and that genetic and non-genetic factors contributed to sPTB. Knowledge of these aspects may aid to improve the management of pregnancies by indicating the lifestyle to be adopted on the basis of sPTB susceptibility.

Nitrate in Drinking Water during Pregnancy and Spontaneous Preterm Birth: A Retrospective Within-Mother Analysis in California

“…Tabacova et al (1998) identified elevated cord blood methemoglobin levels and a higher prevalence of preterm birth among a small sample of women exposed to nitrate during pregnancy. Apoptosis (cell death) induced by hypoxia and oxidative stress has been found to confer risk of spontaneous preterm birth (Tarquini et al 2018). Thus, the prooxidant properties of nitrate are a potential mechanistic explanation for the observed association between nitrate and spontaneous preterm birth.…”

“…Oxidative stress in pregnancy is one of the posited mechanisms for spontaneous preterm birth (Tarquini et al 2018;Aung et al 2019). Despite its prooxidant properties, very few studies have investigated links between gestational nitrate exposure and preterm birth.…”

Identification of a novel gene signature in second-trimester amniotic fluid for the prediction of preterm birth

“…Oxidative stress, characterized by the generation of ROS, is an integral factor in the inflammatory process 35 . Recent studies have demonstrated that oxidative stress plays an important role in infection-induced apoptosis and in the pathogenesis of preterm labor 36 , 37 . LPS triggers inflammatory responses in human gestational tissues by increasing pro-inflammatory cytokines and phospholipid metabolites mediated by activation of the NF-κB pathway.…”

Identification of a novel gene signature in second-trimester amniotic fluid for the prediction of preterm birth

“…Oxidative stress, characterized by the generation of ROS, is an integral factor in the in ammatory process 29 . Recent studies have demonstrated that oxidative stress plays an important role in infectioninduced apoptosis and in the pathogenesis of preterm labor 30,31 . LPS triggers in ammatory responses in human gestational tissues by increasing pro-in ammatory cytokines and phospholipid metabolites mediated by activation of the NF-κB pathway.…”