Role of the Genetic Factors, Detoxication Systems and Oxidative Stress in the Pathogenesis of Endometriosis and Infertility (Review)

Дубинская, Е. Д.; Gasparov, A; Fedorova, T.A.; Lapteva, N V

doi:10.15690/vramn.v68i8.717

Cited by 7 publications

(3 citation statements)

References 45 publications

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“…Many physiological processes can be influenced by OS, which can lead to negative effects or even cause pathological conditions in reproductive systems [ 10 – 13 , 141 ]. One explanation for these pathological conditions may be, at least in part, decreased scavenging capability of antioxidants, which can lead to excessive ROS production.…”

Section: Disturbance Of Redox State Under Pathological Conditions mentioning

confidence: 99%

The Role of Antioxidant Enzymes in the Ovaries

Wang

Chen

et al. 2017

Oxidative Medicine and Cellular Longevity

133

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Proper physiological function of the ovaries is very important for the entire female reproductive system and overall health. Reactive oxygen species (ROS) are generated as by-products during ovarian physiological metabolism, and antioxidants are indicated as factors that can maintain the balance between ROS production and clearance. A disturbance in this balance can induce pathological consequences in oocyte maturation, ovulation, fertilization, implantation, and embryo development, which can ultimately influence pregnancy outcomes. However, our understanding of the molecular and cellular mechanisms underlying these physiological and pathological processes is lacking. This article presents up-to-date findings regarding the effects of antioxidants on the ovaries. An abundance of evidence has confirmed the various significant roles of these antioxidants in the ovaries. Some animal models are discussed in this review to demonstrate the harmful consequences that result from mutation or depletion of antioxidant genes or genes related to antioxidant synthesis. Disruption of antioxidant systems may lead to pathological consequences in women. Antioxidant supplementation is indicated as a possible strategy for treating reproductive disease and infertility by controlling oxidative stress (OS). To confirm this, further investigations are required and more antioxidant therapy in humans has to been performed. BackgroundReactive oxygen species (ROS) are formed during normal metabolism of oxygen and are produced as by-products of aerobic metabolism. A certain amount of ROS production is necessary for gene expression [1], cell signalling [2,3], and redox homeostasis. Scavenging antioxidant systems are indispensable for maintaining an adequate amount of ROS. The balance between the generation and elimination of ROS is a key factor required for almost every metabolic function in mammals. Maintenance of this balance is an important constitutive process and has a particular influence on cell proliferation, differentiation, apoptosis, and death [4]. When ROS production overwhelms the scavenging ability of antioxidants, oxidative stress (OS) occurs. Unfortunately, disruption of this balance can easily result from either an increase in the concentration of ROS or a decrease in scavenging ability. Excessive ROS levels are harmful to the human body and can result in accumulation of oxidative damage in distinct subcellular compartments that exert very toxic effects on DNA, proteins, and lipids. ROS-mediated damage can ultimately influence physiological functions, such as cell signalling pathways and redox-sensitive signalling pathways, and lead to pathological conditions [5].Regarding the female reproductive system, ROS and antioxidants have been recognized as key factors involved in ovarian physiological metabolism. Many studies have investigated the presence of antioxidants and their transcripts in the female reproductive tract [6][7][8]. Previous studies have reported that the balance between ROS and antioxidants greatly influences th...

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Section: Disturbance Of Redox State Under Pathological Conditions mentioning

confidence: 99%

The Role of Antioxidant Enzymes in the Ovaries

Wang

Chen

et al. 2017

Oxidative Medicine and Cellular Longevity

133

View full text Add to dashboard Cite

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“…Two articles were excluded for not reporting exact genotypes [20, 31]. One article was excluded for being a single-arm study [32]. Finally, nine case-control studies [14, 17, 26, 27, 33–37] met the inclusion criteria.…”

Section: Resultsmentioning

confidence: 99%

NAT2 gene polymorphisms and endometriosis risk: A PRISMA-compliant meta-analysis

Wei

Zhang

et al. 2019

PLoS ONE

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ObjectiveEndometriosis is a common chronic, gynecological disease. Despite many studies on the role of N-acetyltransferase 2 (NAT2) in endometriosis, its clinical significance is unclear. In this study, associations between NAT2 phenotypes as well as single nucleotide polymorphisms (SNPs) within NAT2 (i.e. rs1799929, rs1799930, rs1208, and rs1799931) and endometriosis risk were evaluated using a meta-analysis approach.MethodsEmbase, PubMed, ClinicalTrials.gov, CNKI (China National Knowledge Infrastructure), Wanfang databases, Cochrane Library for clinical trials, and Web of Science were searched to identify relevant articles. ORs (odds ratios) and 95% CIs (95% confidence intervals) were used to estimate the associations between NAT2 polymorphisms and endometriosis risk. Heterogeneity among included studies was also assessed. In addition, a subgroup analysis of NAT2 phenotypes and endometriosis risk based on ethnicity was performed.ResultsNine case-control studies met the inclusion criteria. The odds ratio was 2.30 (95% CI: 1.61–3.28) for the NAT2 slow acetylation phenotype versus the intermediate + fast acetylation phenotype in the Asian population. These results suggest that Asian individuals with the NAT2 slow acetylation phenotype have a 130% increased risk of endometriosis. A significant association was also found for rs1799930 (OR = 0.74; 95% CI, 0.59–0.92), suggesting that individuals with this mutant genotype have a 26% decreased risk of endometriosis.ConclusionsThe rs1799930 mutant genotypes are associated with a decreased risk of endometriosis. No statistically significant associations were found between rs1799931, rs1208, or rs1799929 and endometriosis. Based on a subgroup analysis based on ethnicity, the NAT2 slow acetylation phenotype was found to increase the risk of endometriosis in Asians. No statistically significant associations were found between the NAT2 slow acetylation phenotype and endometriosis risk in Caucasians. Accordingly, NAT2 phenotypes and SNPs are potential biomarkers for the diagnosis and treatment of endometriosis.

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“…Genetic heterogeneity is another factor that may explain the inconsistent results of previous studies on the association of smoking with ovarian reserve. N-acetyltransferase2 (NAT2) acetylator status (rapid, intermediate, or slow) has been shown to modify the association of smoking with different disease outcomes, with slow acetylators often more susceptible [19][20][21][22][23][24]. Taylor et al reported reduced fecundability among current smokers who are slow acetylators [20]; however, it remains to be established whether these effects on fecundability are modulated through a reduction in ovarian reserve.…”

Section: Introductionmentioning

confidence: 99%

Association between cigarette smoking and ovarian reserve among women seeking fertility care

et al. 2022

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Introduction This study examined the association of smoking with ovarian reserve in a cross-sectional study of 207 women enrolled in the Louisville Tobacco Smoke Exposure, Genetic Susceptibility, and Infertility (LOUSSI) Study and assessed effect modification by NAT2 acetylator phenotype. Methods Information on current smoking status was collected using a structured questionnaire and confirmed by cotinine assay. Serum anti-Müllerian hormone (AMH) levels were used to assess ovarian reserve. Diminished ovarian reserve (DOR) was defined as AMH <1ng/mL. Single nucleotide polymorphisms in the NAT2 gene, which metabolizes toxins found in cigarette smoke, were analyzed to determine NAT2 acetylator status. Linear and logistic regression were used to determine the effects of smoking on ovarian reserve and evaluate effect modification by NAT2. Regression analyses were stratified by polycystic ovary syndrome (PCOS) status and adjusted for age. Results Current smoking status, either passive or active as measured by urinary cotinine assay, was not significantly associated with DOR. For dose-response assessed using self-report, the odds of DOR increased significantly for every additional cigarette currently smoked (Odds ratio, OR:1.08; 95% confidence interval, 95%CI:1.01–1.15); additionally, every 1 pack-year increase in lifetime exposure was associated with an increased odds of DOR among women without PCOS (OR: 1.08 95%CI: 0.99–1.18). These trends appear to be driven by the heavy or long-term smokers. Effect modification by NAT2 genotype was not established. Conclusion A history of heavy smoking may indicate increased risk of diminished ovarian reserve.

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Role of the Genetic Factors, Detoxication Systems and Oxidative Stress in the Pathogenesis of Endometriosis and Infertility (Review)

Cited by 7 publications

References 45 publications

The Role of Antioxidant Enzymes in the Ovaries

The Role of Antioxidant Enzymes in the Ovaries

NAT2 gene polymorphisms and endometriosis risk: A PRISMA-compliant meta-analysis

Association between cigarette smoking and ovarian reserve among women seeking fertility care

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