Recurrent pregnancy loss (RPL) remains a complex reproductive challenge, often linked to oxidative stress (OS) and DNA damage. Emerging evidence indicates that rare earth elements, including ruthenium (Ru), may disrupt cellular redox balance and impair genomic stability, thereby posing a potential reproductive risk. This study aimed to investigate whether elevated serum Ru levels are associated with OS and DNA damage in individuals experiencing RPL. A case–control study was conducted involving women with a history of RPL (n = 30) and healthy pregnant controls (n = 30). OS was assessed by quantifying malondialdehyde (MDA) and glutathione (GSH), while DNA damage was evaluated using 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels. Serum Ru was quantified by Inductively Coupled Plasma Mass Spectrometer. The association between Ru and oxidative/DNA damage markers in both groups was evaluated by Pearson correlation analysis. Serum MDA levels were higher in the RPL group (6.08 ± 0.52 nmol/ml) relative to controls (3.36 ± 0.43 nmol/ml, P < 0.001), while GSH levels were reduced (7.43 ± 0.97 mg/ml as opposed to 8.84 ± 0.61 mg/ml, P < 0.001). Similarly, 8-OHdG concentrations were elevated in RPL (23.90 ± 8.64 ng/ml) versus controls (10.12 ± 3.53 ng/ml, P < 0.001). Serum Ru levels were also significantly increased in RPL women (0.002 ± 0.0001 ppb) as against controls (0.001 ± 0.0001 ppb, P < 0.001). Correlation analysis revealed that in the RPL group, Ru was positively associated with MDA (r = 0.47, P < 0.01) and 8-OHdG (r = 0.47, P < 0.01) and negatively with GSH (r = − 0.8, P < 0.001). In contrast, no significant correlations were observed in controls (MDA: r = 0.17, P = 0.35; GSH: r = 0.05, P = 0.75; 8-OHdG: r = 0.32, P = 0.07). Scatter plots further demonstrated positive trends of Ru with MDA and 8-OHdG, and an inverse association with GSH in RPL women. After adjusting for age, BMI, and parity, serum Ru remained a significant independent predictor of OS and DNA damage in women with RPL. Ru was positively associated with MDA (β = +0.18, 95% CI: 0.10–0.26, P < 0.001) and 8-OHdG (β = +0.72, 95% CI: 0.41–1.03, P < 0.001), and inversely with GSH (β = − 0.60, 95% CI: − 0.62 − 0.90, P < 0.001), explaining 38–63% of the variance. This study demonstrates that women with RPL exhibit elevated serum ruthenium levels, which are strongly associated with enhanced OS, reduced antioxidant defense, and increased DNA damage. The positive correlations of Ru with MDA and 8-OHdG, alongside its inverse association with GSH, underscore its potential role as a contributing factor in RPL pathophysiology. These findings highlight Ru as an independent predictor of oxidative imbalance and genomic instability in RPL, suggesting that monitoring environmental or therapeutic Ru exposure may be critical for reproductive health. Further large-scale studies are warranted to confirm these associations and clarify underlying mechanisms.

Ruthenium and recurrent pregnancy loss: insights into oxidative and genotoxic effects

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2025年10月29日

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May Alrashed

摘要

Recurrent pregnancy loss (RPL) remains a complex reproductive challenge, often linked to oxidative stress (OS) and DNA damage. Emerging evidence indicates that rare earth elements, including ruthenium (Ru), may disrupt cellular redox balance and impair genomic stability, thereby posing a potential reproductive risk. This study aimed to investigate whether elevated serum Ru levels are associated with OS and DNA damage in individuals experiencing RPL. A case–control study was conducted involving women with a history of RPL (n = 30) and healthy pregnant controls (n = 30). OS was assessed by quantifying malondialdehyde (MDA) and glutathione (GSH), while DNA damage was evaluated using 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels. Serum Ru was quantified by Inductively Coupled Plasma Mass Spectrometer. The association between Ru and oxidative/DNA damage markers in both groups was evaluated by Pearson correlation analysis. Serum MDA levels were higher in the RPL group (6.08 ± 0.52 nmol/ml) relative to controls (3.36 ± 0.43 nmol/ml, P < 0.001), while GSH levels were reduced (7.43 ± 0.97 mg/ml as opposed to 8.84 ± 0.61 mg/ml, P < 0.001). Similarly, 8-OHdG concentrations were elevated in RPL (23.90 ± 8.64 ng/ml) versus controls (10.12 ± 3.53 ng/ml, P < 0.001). Serum Ru levels were also significantly increased in RPL women (0.002 ± 0.0001 ppb) as against controls (0.001 ± 0.0001 ppb, P < 0.001). Correlation analysis revealed that in the RPL group, Ru was positively associated with MDA (r = 0.47, P < 0.01) and 8-OHdG (r = 0.47, P < 0.01) and negatively with GSH (r = − 0.8, P < 0.001). In contrast, no significant correlations were observed in controls (MDA: r = 0.17, P = 0.35; GSH: r = 0.05, P = 0.75; 8-OHdG: r = 0.32, P = 0.07). Scatter plots further demonstrated positive trends of Ru with MDA and 8-OHdG, and an inverse association with GSH in RPL women. After adjusting for age, BMI, and parity, serum Ru remained a significant independent predictor of OS and DNA damage in women with RPL. Ru was positively associated with MDA (β = +0.18, 95% CI: 0.10–0.26, P < 0.001) and 8-OHdG (β = +0.72, 95% CI: 0.41–1.03, P < 0.001), and inversely with GSH (β = − 0.60, 95% CI: − 0.62 − 0.90, P < 0.001), explaining 38–63% of the variance. This study demonstrates that women with RPL exhibit elevated serum ruthenium levels, which are strongly associated with enhanced OS, reduced antioxidant defense, and increased DNA damage. The positive correlations of Ru with MDA and 8-OHdG, alongside its inverse association with GSH, underscore its potential role as a contributing factor in RPL pathophysiology. These findings highlight Ru as an independent predictor of oxidative imbalance and genomic instability in RPL, suggesting that monitoring environmental or therapeutic Ru exposure may be critical for reproductive health. Further large-scale studies are warranted to confirm these associations and clarify underlying mechanisms.