Association of Oxidative Stress on Pregnancy

Table 3

Current studies concerning the influence of oxidative stress on congenital malformations.

References	Markers analyzed	Abnormalities investigated	Commentary
Hernández-García et al. [29] (Mexico)	Dichlorofluorescin (DCFH); 3-(p-Aminophenyl) fluorescein (APF); 3-(p-Hydroxyphenyl); Fluorescein (HPF); Hydroethidine (HE); Dihydrorhodamine (DHR); Mono- and diboronated sensors; Boron dipyrromethene difluoride (BODIPY-) based dyes; Hydrocyanines	Cell development—early embryogenesis	Review: uncertain and unspecific evidence on the role of ROS in development. Assessment of recent methods to detect ROS in vivo—markers of cellular ROS production in embryos
Dennery [28] (USA)	Reactive oxygen species (ROS)	Human development	Review: impact of redox state on fetal development and placenta; High ROS levels cause impairment fetal development and placental function; Possible therapeutic interventions with antioxidant: Vit C and E—uncertain
Bahado-Singh et al. [37] (USA)	Male gender; Oxidative stress; 8-Hyroxy-2-deoxyguauosine, glutathione, vitamin A	Cyanotic congenital heart disease (CCHD), anencephaly, spina bifida, congenital diaphragmatic hernia (CDH), omphalocele, gastroschisis, limb defects, cleft lip with or without cleft palate (CL/P), and isolated cleft palate	Increased OS in males; Development of CCHD, omphalocele, neural tube, and facial cleft is linked to increased OS; (↑8-hyroxy-2-deoxyguauosine, glutathione) (↓vitamin A)
Perluigi et al. [39] (Italy)	Protein carbonylation; Protein-bound HNE; Reduced glutathione (GSH); Heat shock proteins (HSPs); Thioredoxin (Trx)	Down syndrome	Oxidative damage—early event in DS pathogenesis ≥ deleterious DS phenotypes (abnormal development, neuropathology)
Piccoli et al. [44] (Italy)	Mitochondrial respiratory activity; Reactive oxygen species (ROS)	Down syndrome; Congenital heart defects	Mitochondrial disfunction = ↑ OS ≥fibroblast ≥congenital heart defects in DS
Bahado-Singh et al. [37] (USA)	3-Hydroxybutyretate (oxidative stress marker); 3-Hydroxyisovalerate	Down syndrome	Oxidative stress is thought to be one of the most likely causes of neurotoxicity in DS
Zong et al. [33] (China)	Polymorphisms in glutathione S-transferases (GSTs); GSTA1-69C/T	Recurrent spontaneous abortion (RSA)	No significant association between RSA and GSTs polymorphisms
Gimeno et al., [38] (Spain)	Telomere length (TL); Peroxide levels; GSSH/(glutathione) GSH ratio; Cu/ZnSOD, MnSOD activity; Catalase activity; Glutathione peroxidase activity	Down syndrome	Alteration of SOD1gene expression, Cu/Zn SOD protein levels and other antioxidant enzymes (thioredoxin 1) ≥poor proliferative capability of tissues in DS (telomeric attrition, increased expression of Rcan1) - > ↑OS - > pathophysiology of DS
Mukhopadhyay et al. [42] (India)	Malondialdehyde (MDA); Protein carbonyl (PC); Vitamin C; Reduced glutathione (GSH)	Tracheesophageal fistula (TEF); Anorectal malformation (ARM); Intestinal atresia (IA)	↑ MDA, PC (products of lipid and protein oxidation) = pathophysiology involves OS; Treatment with antioxidants = useful as a preventive therapy
Sakai et al. [41] (Japan)	Reactive oxygen species (ROS); N-Acetyl-cysteine (NAC)	Treacher Collins syndrome	Tcof1 haploinsufficiency results in OS-induced DNA damage and neuroepithelial cell death; Maternal treatment with antioxidants minimizes cell death in the neuroepithelium and substantially ameliorates/prevents the pathogenesis of craniofacial anomalies in Tcof1^+/− mice
Yuan et al. [48] (China)	8-Hydroxy-2-deoxyguanosine (8-OHdG), protein carbonyl (PC), and 8-iso-prostaglandin F2α (8-iso-PGF2α)	Neural tube defects (NTDs)	↑ 8-OhdG—without folic acid supplements during the periconceptional period; ↑ 8-OhdG—pregnancies affected by NTDs
Moore et al. [55] (Turkey)	Reactive oxygen species (ROS)	Congenital malformations	OS = harmful radicals attacking biological molecules: DNA, lipids, proteins
Ozsurekci et al. [56] (Japan)	Reactive oxygen species (ROS); TCOF1 gene	Treacher Collins syndrome (TCS)	Review: role of Tcof1 mutation in embryonic craniofacial development; Genetic and environmental factors ≥severity of craniofacial abnormalities, prospect for prenatal prevention of craniofacial anomalies
Maciejczyk et al. [40] (Poland)	Total antioxidant capacity (TAC); Malondialdehyde (MDA)	Ataxia-telangiectasia (A-T),; Bloom syndrome (BS); Nijmegen breakage syndrome (NBS)	A-T, BS, and NBS may be considered mitochondrial diseases. Excess activity of antioxidant enzymes and an insufficient amount of low molecular weight antioxidants indicate new pharmacological strategies for treatment.
Pietryga et al. [34] (Poland)	Glutathione (GSH); Glutathione S-transpherase (GST); S-Nitrosothiols (RSNO); Trolox equivalent antioxidant capacity (TEAC); Total protein (TP); Nitrites	Chromosomal aberrations; Congenital malformations	↑ TP, GST, TEAC, and ↓ GSH correlated with the risk of chromosomal aberrations and congenital malformations
Liu et al. [43] (China)	Lead (Pb); Aluminum (Al); Malondialdehyde (MDA); Supeoxide dismutase (SOD); Glutathione peroxidase (GSH-Px)	Congenital heart disease	Heavy metals ≥↑ oxidative stress ≥congenital heart disease
Cim et al. [46] (Turkey)	Glutathione (GSH); Catalase (CAT); Malondialdehyde (MDA)	Congenital malformations of the central nervous system	↑ MDA; ↓ GSH and CAT = ↑ OS in amniotic fluid—associated with neural tube defects
Laforgia et al. [36] (Italy)	Oxidative stress; Reactive oxygen species (ROS); Antioxidants	Down syndrome; Heart malformation; Neural tube effect	Review: fetal tissue—sensitive to oxidative damage; OS + impaired antioxidant activity = congenital malformations; Antioxidants therapeutic approaches
Lin et al. [47] (China)	Benzo[α] pyrene (BaP); Reactive oxygen species (ROS); Superoxide dismutase (SOD); Glutathione peroxidase (GPx); Catalase (CAT); 8-hydroxy2deoxyguanosine Total antioxidant capacity (TAC); Malondialdehyde (MDA)	Neural tube defects	BaP exposure ≥↑ OS, apoptosis ≥NTDs; Protective effect of vitamin E
Engineer et al. [45] (Canada)	Review; Nitric oxide (NO); Nitric oxide synthase (eNOS); ROS; 8-hydroxyguanosine (8-OHG)	Congenital heart disease	eNOS and NO—critical for property morphogenesis of all major components of the developing heart; ↑ ROS—nonspecific damage and permanent functional changes; 8-OHG—RNA damage causative factor; Hyperglycemia = ↑ROS; Treatment with Vit E and C = ↓ rate and severity of CHD