Shen, L., Liang, C., Li, D., Zhang, Z., Wang, X., Jiang, T., Su, X., Yin, T., Zou, W., Wang, X., Liu, Y., Liang, D., Wei, Z., Cao, Y., & Ji, D. (2023). The association between exposure to multiple toxic metals and the risk of endometriosis: Evidence from the results of blood and follicular fluid. The Science of the total environment, 855, 158882. https://doi.org/10.1016/j.scitotenv.2022.158882
Shen L, Liang C, Li D, Zhang Z, Wang X, Jiang T, Su X, Yin T, Zou W, Wang X, Liu Y, Liang D, Wei Z, Cao Y, Ji D. The association between exposure to multiple toxic metals and the risk of endometriosis: Evidence from the results of blood and follicular fluid. The Science of the total environment. 2023;855:158882. doi:10.1016/j.scitotenv.2022.158882
Shen, L., et al. "The association between exposure to multiple toxic metals and the risk of endometriosis: Evidence from the results of blood and follicular fluid." The Science of the total environment, vol. 855, 2023, pp. 158882.
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Second Hospital of Shanxi Medical University03tn5kh37
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Abstract
Background
Endometriosis affects up to 10 % of women of reproductive age and can lead to infertility. Research investigating whether combined exposure to arsenic (As), cadmium (Cd), lead (Pb) and mercury (Hg) is related to an increased risk of endometriosis, especially using different biological samples to validate the association, is very limited.
Objective
This investigation aimed to evaluate the associations between the concentrations of As, Cd, Pb and Hg in blood and follicular fluid and the risk of endometriosis.
Methods
A total of 609 endometriosis cases and controls seen at the reproductive center of the First Affiliated Hospital of Anhui Medical University in Hefei, China, between April 2020 and December 2021 were included in our study. Blood (217 cases and 234 controls) and follicular fluid (182 cases and 203 controls) samples were collected from these subjects. The concentrations of Cd, Hg, As and Pb in the blood and follicular fluid were determined by inductively coupled plasma-mass spectrometry (ICP-MS). Unconditional logistic regression models were used to assess the associations between Cd, Hg, As or Pb levels and the risk of endometriosis; Bayesian kernel machine regression (BKMR) was used to evaluate the combined effect of metals on the risk of endometriosis.
Results
We found significant associations between blood concentrations of As (highest vs. lowest tertile: aOR = 5.53, 95 % CI: 2.97, 10.30), Cd (second vs. lowest tertile: aOR = 1.96, 95 % CI: 1.07, 3.58; highest vs. lowest tertile: aOR = 3.21, 95 % CI: 1.79, 5.77), Pb (highest vs. lowest tertile: aOR = 2.73, 95 % CI: 1.56, 4.78) and Hg (high-level group vs. low-level group: aOR = 13.10, 95 % CI: 6.74, 25.44; second vs. lowest tertile: aOR = 15.27, 95 % CI: 4.96, 46.97; highest vs. lowest tertile: aOR = 35.66, 95 % CI: 11.99, 106.08) and increased risk of endometriosis adjusting for confounders. Follicular fluid As (highest vs. lowest tertile: aOR = 2.42, 95 % CI: 1.35, 4.33), Hg (highest vs. lowest tertile: aOR = 1.86, 95 % CI: 1.05, 3.29), Cd (second vs. lowest tertile: aOR = 2.45, 95 % CI: 1.29, 4.65; highest vs. lowest tertile: aOR = 3.12, 95 % CI: 1.67, 5.83), and Pb (second vs. lowest tertile: aOR = 1.97, 95 % CI: 1.11, 3.52) concentrations were positively associated with endometriosis risk. The BKMR analyses showed linear associations between the metal mixtures and the risk of endometriosis. Both in blood and in follicular fluid, As exhibited the highest contribution.
Conclusion
The data from this study suggest that toxic metals, individually and as a mixture, play a role in the risk of endometriosis, thus providing a novel idea for endometriosis prevention.
Sun Y et al., 2024·Ther Adv Reprod Health·Free full text on PubMed Central
Chronic endometritis (CE), frequently asymptomatic, is associated with female infertility. Fallopian tube obstruction (FTO) is also one of the factors contributing to female infertility. More than 90% of cases of proximal FTO can be successfully treated after fallopian tubal recanalization (FTR) and the spontaneous pregnancy rate of treated women after FTR is only about 30%. Potential factors affecting the success rate of FTR remain unclear. We speculate that CE may be one of the reasons affecting the recanalization of the fallopian tubes. To identify the correlation between CE and FTO, as well as the influence of CE on pregnancy outcomes following FTR.
Retrospective observational study. We retrospectively analyzed 498 women of childbearing age who underwent laparoscopy and hysteroscopy surgery for infertility. Endometrial samples were collected during surgery for CD138 immunohistochemistry staining for the diagnosis of CE. Based on the results of the tubal patency test, they were divided into two groups: the fallopian tubal patency group and the proximal FTO group. The prevalence of CE was compared between these two groups. All women with FTO underwent FTR during the operation until successful treatment was achieved. Pregnancy outcomes were assessed after a 12-month follow-up period following the procedures. Logistic regression was used to analyze factors that might affect pregnancy after FTR. The prevalence of CE in women with tubal obstruction was 30.5%, which was significantly higher than that in the fallopian tubal patency group (10.75%), p < 0.001. After FTR, the prevalence of CE in non-pregnant women was 40.18%, which was higher than that in pregnant women (40.18% vs 13.11%), and the difference was significant (p < 0.001). Multiple regression analysis showed that CE was a significant risk factor for FTO (OR: 2.54, 95% CI: 1.368-4.717, p < 0.05). In addition, CE was identified as a risk factor for infertility after FTR (OR: 4.730, 95% CI: 2.012-11.122). The presence of CE seems to decrease the likelihood of achieving spontaneous pregnancy following FTR. This observation underscores the clinical importance of early detection and treatment of CE, emphasizing the necessity for immediate intervention to prevent potential fertility complications.
Perinatal and childhood adverse outcomes associated with assisted reproductive technology (ART) has been reported, but it remains unknown whether the initial leukocyte telomere length (LTL), which is an indicator of age-related phenotypes in later life, is affected. Here, we estimated the LTLs of 1,137 individuals from 365 families, including 202 children conceived by ART and 205 children conceived spontaneously from two centers of the China National Birth Cohort, using whole-genome sequencing (WGS) data. One-year-old children conceived by ART had shorter LTLs than those conceived spontaneously (beta, -0.36; P = 1.29 × 10-3) after adjusting for plurality, sex and other potential confounding factors. In particular, blastocyst-stage embryo transfer was associated with shorter LTL (beta, -0.54, P = 2.69 × 10-3) in children conceived by ART. The association was validated in 586 children conceived by ART from five centers using different LTL quantification methods (that is, WGS or qPCR). Blastocyst-stage embryo transfer resulted in shorter telomere lengths in mice at postnatal day 1 (P = 2.10 × 10-4) and mice at 6 months (P = 0.042). In vitro culturing of mice embryos did not result in shorter telomere lengths in the late cleavage stage, but it did suppress telomerase activity in the early blastocyst stage. Our findings demonstrate the need to evaluate the long-term consequences of ART, particularly for aging-related phenotypes, in children conceived by ART.
To provide an up-to-date comparison of pregnancy-related complications and adverse pregnancy outcomes of multiple pregnancies generated with assisted reproductive technology (ART) vs. spontaneous conception. Meta-analysis. University-affiliated teaching hospital.Patient(s)Multiple pregnancies conceived by ART or naturally.Intervention(s)Searches through October 2014 were conducted on PubMed, Google Scholar, Cochrane Libraries, China Biology Medicine disc, Chinese Scientific Journals Fulltext Database, China National Knowledge Infrastructure, and Wanfang Data, to identify studies that met prestated inclusion criteria. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. Subgroup analysis was performed to explore potential heterogeneity moderators.Main outcome measure(s)Pregnancy-related complications and adverse pregnancy outcomes.Result(s)Thirty-nine cohort studies involving 146,008 multiple births were included in the meta-analysis. Multiple pregnancies from ART were associated with a higher risk of premature rupture of membranes (relative risk [RR] = 1.20, 95% confidence interval [CI]: 1.05-1.37; I(2) = 15%); pregnancy-induced hypertension (RR = 1.11, 95% CI: 1.04-1.19; I(2) = 6%); gestational diabetes mellitus (RR = 1.78, 95% CI: 1.25-2.55; I(2) = 42%); preterm birth (RR = 1.08, 95% CI: 1.03-1.14; I(2) = 83%); very preterm birth (RR = 1.18, 95% CI: 1.04-1.34; I(2) = 79%); low birth weight (RR = 1.04, 95% CI: 1.01-1.07; I(2) = 47%); very low birth weight (RR = 1.13, 95% CI: 1.01-1.25; I(2) = 62%); and congenital malformation (RR = 1.11, 95% CI: 1.02-1.22; I(2) = 30%). The relevant heterogeneity moderators have been identified by subgroup analysis. Sensitivity analysis yielded similar results. No evidence of publication bias was observed.Conclusion(s)Although the role of potential bias and evidence of heterogeneity should be carefully evaluated, the present study suggests that multiple pregnancies generated via ART, vs. spontaneous conception, are associated with higher risks of pregnancy-related complications and adverse pregnancy outcomes. Further research is needed to determine which aspect of ART poses the most risk and how this risk can be minimized.
Lin J et al., 2023·Frontiers in public health·Free full text on PubMed Central
Infertility has been confirmed as a significant medical and social problem. Heavy metal exposure refers to a risk factor for infertility, which is capable of damaging the reproductive system of males and females. However, heavy metal exposure and female infertility have rarely been investigated. The aim of this study was to analyze the association between heavy metal exposure and female infertility. A cross-sectional study using data from three cycles of the National Health and Nutrition Examination Survey (NHANES, 2013-2018) was performed. Female infertility was evaluated by positive responses to question rhq074 in the questionnaire. Cadmium (Cd), lead (Pb), mercury (Hg), and arsenic (As) levels in blood or urine were examined by inductively coupled plasma mass spectrometry. The correlation between heavy metal and female infertility was analyzed through weighted logistic regression. A total of 838 American women aged 20-44 years were covered in the study. Among all participants, 112 (13.37%) women were subjected to infertility. Urinary Cd and urinary As levels were significantly higher in infertile women than in control women (P < 0.05, P < 0.05). Urinary As showed a positive correlation with the prevalence of female infertility, and the risk of infertility rose with the increase of urinary As levels (P for trend = 0.045). Urinary Cd was associated with female infertility in some weighted logistic regression (Crude, Q2: OR = 3.99, 95% CI 1.82, 8.74, Q3: OR = 2.90, 95% CI 1.42, 5.92. Model 1, Q2: OR = 3.68, 95% CI 1.64, 8.27, Q3: OR = 2.33, 95% CI 1.13, 4.48. Model 2, Q2: OR = 4.11, 95% CI 1.63, 10.07, Q3: OR = 2.44, 95% CI 1.07, 5.53. Model 3, Q2: OR = 3.77, 95% CI 1.52, 9.35). Moreover, blood Pb (OR = 1.52, 95% CI 1.07, 2.16), urinary Pb (OR = 1.68, 95% CI 1.11, 2.55), and urinary As (OR = 1.02, 95% CI 1.00, 1.03) were positively correlated with the risk of infertility in women aged 35-44 years. The blood Pb (OR = 1.67, 95% CI 1.16, 2.40, 2.49) and urinary Pb (OR = 1.54, 95% CI 1.00, 2.38) in women with BMI ≥25 were positively correlated with the risk of infertility. Urinary As was significantly associated with female infertility, and the risk of infertility increased with higher urinary As levels. To some extent, urinary Cd was correlated with infertility. Blood/urine Pb was related to infertility in advanced age and overweight/obese women. The results of this study need to be further validated in future prospective studies.
Pollack AZ et al., 2013·Reprod Toxicol·Free full text on PubMed Central
There has been limited study of trace elements and endometriosis. Using a matched cohort design, 473 women aged 18-44 years were recruited into an operative cohort, along with 131 similarly aged women recruited into a population cohort. Endometriosis was defined as surgically visualized disease in the operative cohort, and magnetic resonance imaging diagnosed disease in the population cohort. Twenty trace elements in urine and three in blood were quantified using inductively coupled plasma mass spectrometry. Logistic regression estimated the adjusted odds (aOR) of endometriosis diagnosis for each element by cohort. No association was observed between any element and endometriosis in the population cohort. In the operative cohort, blood cadmium was associated with a reduced odds of diagnosis (aOR=0.55; 95% CI: 0.31, 0.98), while urinary chromium and copper reflected an increased odds (aOR=1.97; 95% CI: 1.21, 3.19; aOR=2.66; 95% CI: 1.26, 5.64, respectively). The varied associations underscore the need for continued research.
Buck Louis GM et al., 2012·Environ Health Perspect·Free full text on PubMed Central
An equivocal literature exists regarding the relation between persistent organochlorine pollutants (POPs) and endometriosis in women, with differences attributed to methodologies. We assessed the association between POPs and the odds of an endometriosis diagnosis and the consistency of findings by biological medium and study cohort. Using a matched cohort design, we assembled an operative cohort of women 18-44 years of age undergoing laparoscopy or laparotomy at 14 participating clinical centers from 2007 to 2009 and a population-based cohort matched on age and residence within a 50-mile catchment area of the clinical centers. Endometriosis was defined as visualized disease in the operative cohort and as diagnosed by magnetic resonance imaging in the population cohort. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for each POP in relation to an endometriosis diagnosis, with separate models run for each medium (omental fat in the operative cohort, serum in both cohorts) and cohort. Adjusted models included age, body mass index, breast-feeding conditional on parity, cotinine, and lipids. Concentrations were higher in omental fat than in serum for all POPs. In the operative cohort, γ-hexachlorocyclohexane (γ-HCH) was the only POP with a significant positive association with endometriosis [per 1-SD increase in log-transformed γ-HCH: adjusted OR (AOR) = 1.27; 95% CI: 1.01, 1.59]; β-HCH was the only significant predictor in the population cohort (per 1-SD increase in log-transformed β-HCH: AOR = 1.72; 95% CI: 1.09, 2.72). Using a matched cohort design, we found that cohort-specific and biological-medium-specific POPs were associated with endometriosis, underscoring the importance of methodological considerations when interpreting findings.
Louis GMB et al., 2012·Epidemiology·Free full text on PubMed Central
Environmental chemicals may be associated with endometriosis. No published research has focused on the possible role of perfluorochemicals (PFCs) despite their widespread presence in human tissues. We formulated two samples. The first was an operative sample comprising 495 women aged 18-44 years scheduled for laparoscopy/laparotomy at one of 14 participating clinical sites in the Salt Lake City or San Francisco area, 2007-2009. The second was a population-based sample comprising 131 women matched to the operative sample on age and residence within a 50-mile radius of participating clinics. Interviews and anthropometric assessments were conducted at enrollment, along with blood collection for the analysis of nine PFCs, which were quantified using liquid chromatography-tandem mass spectrometry. Endometriosis was defined based on surgical visualization (in the operative sample) or magnetic resonance imaging (in the population sample). Using logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) for each PFC (log-transformed), adjusting for age and body mass index, and then parity. Serum perfluorooctanoic acid (PFOA; OR = 1.89 [95% CI = 1.17-3.06]) and perfluorononanoic acid (2.20 [1.02-4.75]) were associated with endometriosis in the operative sample; findings were moderately attenuated with parity adjustment (1.62 [0.99-2.66] and 1.99 [0.91-4.33], respectively). Perfluorooctane sulfonic acid (1.86 [1.05-3.30]) and PFOA (2.58 [1.18-5.64]) increased the odds for moderate/severe endometriosis, although the odds were similarly attenuated with parity adjustment (OR = 1.50 and 1.86, respectively). Select PFCs were associated with an endometriosis diagnosis. These associations await corroboration.
Lifestyle and Environment › Environmental Exposures › Heavy Metals
PMID 36155031 36155031 DOI 10.1016/j.scitotenv.2022.158882 10.1016/j.scitotenv.2022.158882 Shen et al. 2023, Shen 2023
Cite this article
Shen, L., Liang, C., Li, D., Zhang, Z., Wang, X., Jiang, T., Su, X., Yin, T., Zou, W., Wang, X., Liu, Y., Liang, D., Wei, Z., Cao, Y., & Ji, D. (2023). The association between exposure to multiple toxic metals and the risk of endometriosis: Evidence from the results of blood and follicular fluid. The Science of the total environment, 855, 158882. https://doi.org/10.1016/j.scitotenv.2022.158882
Shen L, Liang C, Li D, Zhang Z, Wang X, Jiang T, Su X, Yin T, Zou W, Wang X, Liu Y, Liang D, Wei Z, Cao Y, Ji D. The association between exposure to multiple toxic metals and the risk of endometriosis: Evidence from the results of blood and follicular fluid. The Science of the total environment. 2023;855:158882. doi:10.1016/j.scitotenv.2022.158882
Shen, L., et al. "The association between exposure to multiple toxic metals and the risk of endometriosis: Evidence from the results of blood and follicular fluid." The Science of the total environment, vol. 855, 2023, pp. 158882.