Mediating effect of oxidative stress on association between nicotine and unexplained recurrent spontaneous abortion

Dandan LI; Zhonghua MENG; Yingli QU; Yuanyuan LI; Huijuan ZHU; Zhong LIU; Feng ZHAO

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Mediating effect of oxidative stress on association between nicotine and unexplained recurrent spontaneous abortion

VernacularTitle:氧化应激在尼古丁与不明原因复发性流产的中介效应
Author: Dandan LI ¹ ; Zhonghua MENG ² ; Yingli QU ¹ ; Yuanyuan LI ³ ; Huijuan ZHU ⁴ ; Zhong LIU ² ; Feng ZHAO ¹
Author Information

1. National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China.
2. Physical and Chemical Laboratory, Shandong Jinan Center for Disease Control and Prevention, Jinan, Shandong 250021, China.
3. Big Data Office, Beijing Tongzhou District Center for Disease Control and Prevention, Beijing 101199, China.
4. Second Department of Chemical Drug Monitoring and Evaluation, Center for Drug Reevaluation, National Medical Products Administration, Beijing 100022, China.
Publication Type:Selectedarticle
Keywords: nicotine; unexplained recurrent spontaneous abortion; mediating effect; 8-hydroxy-2’-deoxyguanosine; 8-iso-prostaglandin F2α
From: Journal of Environmental and Occupational Medicine 2022;39(5):512-518
CountryChina
Language:Chinese
Abstract: Background Previous studies have confirmed that nicotine exposure is an independent risk factor for miscarriage, but it is not clear whether nicotine causes unexplained recurrent spontaneous abortion (URSA) through oxidative stress. Objective To explore potential mediating effect of oxidative stress on the relationship between nicotine exposure and URSA. Methods Using a 1∶1 matched case-control study, 88 patients with URSA visiting Beijing Obstetrics and Gynecology Hospital affiliated to Capital Medical University from April to October in 2018 were selected as the case group, and 88 pregnant women without adverse pregnancy outcomes and seeking induced abortion in the outpatient clinic of the same hospital were selected as the control group. The levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-iso-prostaglandin F2α (8-iso-PGF2α) in urine were determined by enzyme-linked immunosorbent assay, and the level of urinary nicotine was determined by gas chromatography-mass spectrometry. Conditional logistic regression was used to analyze the associations of nicotine, 8-OHdG, and 8-iso-PGF2α with the risk of URSA. Multiple linear regression was used to analyze the association of nicotine with 8-OHdG and 8-iso-PGF2α. The potential mediating effect of oxidative stress on URSA after nicotine exposure was explored by dichotomous mediating model. Results The median concentrations (creatinine corrected) of nicotine, 8-OHdG, and 8-iso-PGF2α in urine of the case group were 7.78, 4.84, and 44.10 μg·g⁻¹, respectively, while those of the control group were 6.48, 3.34, and 29.39 μg·g⁻¹, respectively. The concentrations of nicotine, 8-OHdG, and 8-iso-PGF2α in urine of the case group were all higher than those of the control group (P < 0.05). The results of conditional logistic regression model showed that after adjusting selected confounding factors, compared with the Q₁ groups of nicotine and 8-iso-PGF2α, the OR (95%CI) values of URSA in the Q₄ groups were 4.20 (1.33-13.29) and 6.25 (1.66-23.59), respectively. Compared with the Q₁ group of 8-OHdG, the OR (95%CI) values of URSA in the Q₁, Q₂, and Q₃ groups were 5.47 (1.43-20.93), 4.24 (1.28-14.07), and 6.36 (1.82-22.28), respectively. The results of multiple linear regression showed that after adjusting confounding factors, there was a positive correlation between urinary nicotine and 8-OHdG in both the case group and the control group, and the b (95%CI) values were 0.76 (0.67-0.86) and 0.81 (0.67-0.95) respectively; there was a positive correlation between urinary nicotine and 8-iso-PGF2α in both the case group and the control group, and the b (95%CI) values were 0.65 (0.55-0.75) and 0.76 (0.64-0.87), respectively. The results of dichotomous mediating analysis showed that the mediating effect of 8-iso-PGF2α and its 95%CI on the relationship between nicotine exposure and URSA was 1.518 (0.749-2.311). Conclusion Internal nicotine exposure is a risk factor for URSA and is positively correlated with oxidative stress, and it may lead to URSA through lipid peroxidation damage.