Oxidative/nitrosative stress increased the risk of recurrent pregnancy loss-Taiwan Recurrent Pregnancy Loss and Environmental Study (TREPLES)

Yu-Jung Lin; Wei-Hsiang Chang; Pao-Lin Kuo; Hsin-Chang Chen; Wan-Ting Chang; Po-Chin Huang

doi:10.1016/j.redox.2023.102940

Oxidative/nitrosative stress increased the risk of recurrent pregnancy loss-Taiwan Recurrent Pregnancy Loss and Environmental Study (TREPLES)

Redox Biol. 2023 Dec:68:102940. doi: 10.1016/j.redox.2023.102940. Epub 2023 Oct 19.

Authors

Yu-Jung Lin¹, Wei-Hsiang Chang², Pao-Lin Kuo³, Hsin-Chang Chen⁴, Wan-Ting Chang¹, Po-Chin Huang⁵

Affiliations

¹ National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli, Taiwan.
² Department of Food Safety/ Hygiene and Risk Management, College of Medicine, National Cheng Kung University, Tainan, 704, Taiwan.
³ Department of Obstetrics and Gynecology, National Cheng Kung University Hospital and College of Medicine, Tainan, Taiwan; Department of Obstetrics and Gynecology, Eda Hospital, Kaohsiung, Taiwan.
⁴ Department of Chemistry, Tunghai University, Taichung, Taiwan.
⁵ National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan; Research Center for Precision Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: pchuang@nhri.edu.tw.

Abstract

Objective: Oxidative stress biomarkers (OSBs) may be strongly associated with disease progression and recurrent pregnancy loss (RPL). However, the research on associations of most OSBs (e.g., 8-nitroguanine [8-NO₂Gua] and 4-hydroxy-2-nonenal-mercapturic acid [HNE-MA]) with RPL is limited. Therefore, we aimed to investigate the effect of OSBs exposure on RPL risk by performing a case-control study.

Material and methods: We use our established dataset, Taiwan Recurrent Pregnancy Loss and Environmental Study (TREPLES), which included 514 Taiwanese reproductive age women (aged 20-50 years; 397 cases and 117 controls) from National Cheng Kung University Hospital. RPL is clinically defined by a history of two or more consecutive miscarriages, where a miscarriage is defined as the termination of pregnancy before 20 weeks of gestation. The urinary levels of several OSBs (e.g., 8-hydroxy-2'-deoxyguanosine [8-OHdG], 8-NO₂Gua, 8-isoprostaglandin F_{2α [}8-isoPGF2_α], and HNE-MA) and malondialdehyde (MDA) were measured using isotope dilution liquid chromatography-tandem mass spectrometry and thiobarbituric acid reactive substances, respectively.

Results: The median levels of 8-NO₂Gua (6.15 vs. 3.76 ng/mL) and HNE-MA (30.12 and 21.54 ng/mL) were significantly higher in the RPL group than in the control group. By categorizing the OSBs data into tertiles, after we adjusted for age and urine creatinine levels discovered that the RPL risk associated with 8-NO₂Gua and HNE-MA levels in the third tertile were approximately 2 times higher than those in the first tertile (8-NO₂Gua, adjusted OR = 3.27, 95 % CI = 1.66-6.43; HNE-MA, adjusted OR = 1.96, 95 % CI = 1.05-3.64; p < 0.05). These findings suggest that the oxidative stress biomarkers of 8-NO₂Gua and HNE-MA are risk factors for RPL.

Conclusion: Our findings indicate that specific OSBs are associated with an increased RPL risk, suggesting that reducing OSB levels can improve RPL risk. Nevertheless, more studies on preventive medicine are required to understand the exposure sources and adverse outcome pathways of OSBs associated with RPL.

Keywords: DNA damage; Lipid peroxidation; Nitrative stress; Oxidative stress; Recurrent pregnancy loss.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

8-Hydroxy-2'-Deoxyguanosine / urine
Abortion, Habitual* / etiology
Abortion, Habitual* / metabolism
Adult
Aldehydes / metabolism
Aldehydes / urine
Biomarkers* / urine
Case-Control Studies
Female
Guanine / analogs & derivatives*
Guanine / metabolism
Guanine / urine
Humans
Middle Aged
Nitrosative Stress*
Oxidative Stress*
Pregnancy
Risk Factors
Taiwan
Young Adult

Substances

Biomarkers
Guanine
Aldehydes
4-hydroxy-2-nonenal
8-nitroguanine
8-Hydroxy-2'-Deoxyguanosine