Exposures to drinking water disinfection byproducts and kidney function in Chinese women.

BACKGROUND: Disinfection byproducts (DBPs), the ubiquitous contaminants in drinking water, have been shown to impair renal function in experimental studies. However, epidemiological evidence is sparse. OBJECTIVE: To investigate exposures to DBPs in associations with renal function among women. METHODS: A total of 920 women from December 2018 to January 2020 were abstracted from the Tongji Reproductive and Environmental (TREE) Study, an ongoing cohort study in Wuhan, China. Urine samples were gathered at baseline recruitment and analyzed for dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) as biomarkers of DBP exposures. Serum uric acid (UA), creatinine, and estimated glomerular filtration rate (eGFR) were measured as indicators of renal function. Multivariate linear regression and restricted cubic spline (RCS) models were conducted to assess urinary DCAA and TCAA concentrations in associations with renal function indicators. Stratified analyses by age and body mass index (BMI) were also performed. RESULTS: We found null evidence of urinary TCAA in associations with renal function indicators. However, elevated urinary DCAA tertiles were related to decreased eGFR (ß = -1.78%, 95% CI: 3.21%, -0.36%, comparing the upper vs. lower tertile; P for trend = 0.01). This inverse association still existed when urinary DCAA concentration was treated as a continuous variable, and the dose-response relationship was linear based on the RCS model (P for overall association = 0.002 and P for non-linear associations = 0.44). In the stratified analyses, we found an association of urinary DCAA concentration with decreased UA level among women <30 years but an association with increased UA level among women ≥30 years (P for interaction = 0.04). CONCLUSION: Urinary DCAA but not TCAA was associated with impaired renal function among women undergoing assisted reproductive technology.

Associations of exposure to disinfection by-products with blood coagulation parameters among women: Results from the Tongji reproductive and environmental (TREE) study.

BACKGROUND: Experimental studies have shown that disinfection byproducts (DBPs) induce coagulotoxicity, but human evidence is scarce. OBJECTIVE: This study aimed to explore the relationships of DBP exposures with blood coagulation parameters. METHODS: Among 858 women from the Tongji Reproductive and Environmental (TREE) study, urinary dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) were detected as internal biomarkers of DBP exposures. We measured activated partial thromboplastin time (APTT), fibrinogen (Fbg), international normalized ratio (INR), prothrombin time (PT), and thrombin time (TT) as blood coagulation parameters. Multivariable linear regression models were utilized to estimate the relationships between urinary DCAA and TCAA and blood coagulation parameters. The effect modifications by demographic and lifestyle characteristics were further explored. RESULTS: Elevated tertiles of urinary DCAA concentrations were associated with increased PT and INR (11.29%, 95% CI: 1.66%, 20.92% and 0.99%, 95% CI: 0.08%, 1.90% for the third vs. first tertile, respectively; both P for trends < 0.05). Stratification analysis showed that the positive associations were only observed among younger (< 30 years), leaner (body mass index < 24.0 kg/m2), and non-passive smoking women. Moreover, elevated tertiles of urinary TCAA concentrations in positive associations with PT and INR were observed among younger women (17.89%, 95% CI: 2.50%, 33.29% and 1.82%, 95% CI: 0.34%, 3.30% for the third vs. first tertile, respectively; both P for trends < 0.05) but not among older women (both P for interactions < 0.05). CONCLUSION: Higher levels of urinary DCAA and TCAA are associated with prolonged clotting time among women.

Within-day variability, predictors, and risk assessments of exposure to parabens among Chinese adult men.

BACKGROUND: Parabens, as suspected endocrine disruptors, are widely used in personal care products and pharmaceuticals. However, variability, predictors, and risk assessments of human exposure to parabens are not well characterized. OBJECTIVE: To evaluate within-day variability, predictors, and risk assessments of exposure to parabens among Chinese adult men. METHODS: We measured four parabens including methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP) in repeated urine samples from 850 Chinese adult men. We examined the variability by intraclass correlation coefficients (ICCs) and identified the predictors by multivariable linear mixed models. We assessed risks of paraben exposures based on the estimated daily intake (EDI). RESULTS: The four parabens were detected in >76% of urinary samples. We observed fair to good to high reproducibility (ICCs: 0.71 to 0.86) for urinary paraben concentrations within one day. Use of facial cleanser was associated with higher four urinary paraben concentrations. Increasing age, taking medicine, intravenous injection, and interior decoration in the workplace were related to higher urinary concentrations of specific parabens. Smoking and drinking were associated with lower urinary concentrations of specific parabens. The maximum EDIs for the four parabens ranged from 13.76 to 848.68 µg/kg bw/day, and 0.9% of participants had the hazard quotient values > 1 driven by PrP exposure. CONCLUSIONS: Urinary paraben concentrations were less variable within one day. Several lifestyle characteristics including use of facial cleanser and pharmaceuticals may contribute to paraben exposures.

New polyketides from the basidiomycetous fungus Pholiota sp.

Two new polyketides, pholiotones B and C (1 and 2), and four known compounds, trichodermatide D (3), vermistatin (4), dehydroaltenuene A (5) and terpestacin (6) were isolated from the crude extract of Pholiota sp. Their structures were identified by NMR and MS spectroscopic data. The absolute configurations of compounds 1 and 2 were elucidated by modified Mosher's method, electronic circular dichroism (ECD) calculations and 13C NMR calculations as well as DP4+ probability analyses. All the compounds were evaluated for their antifungal and cytotoxicity.

Associations of sleep characteristics with outcomes of IVF/ICSI treatment: a prospective cohort study.

STUDY QUESTION: Are sleep characteristics associated with outcomes of IVF/ICSI treatment? SUMMARY ANSWER: Nocturnal sleep <7 h/night and disturbed sleep are related to impaired oocyte and embryo yield, while longer nocturnal sleep might reduce the chance of a successful pregnancy, and the associations between nocturnal sleep duration and IVF/ICSI outcomes are modified by maternal age and subjective sleep quality. WHAT IS KNOWN ALREADY: Disturbed sleep and circadian rhythm contribute to impaired fecundity in the general population, but the effects of sleep characteristics on IVF/ICSI outcomes are largely unknown. STUDY DESIGN, SIZE, DURATION: This study was conducted among 1276 women undergoing IVF/ICSI treatment between December 2018 and September 2019 based on the Tongji Reproductive and Environmental cohort. Owing to the limited number of multiple cycles, we included only the outcomes of their first IVF/ICSI cycle in the current analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data on sleep characteristics were collected via questionnaires on the day of oocyte retrieval. IVF/ICSI outcomes were abstracted from medical records. Quasi-Poisson, quasi-binomial or logistic regression models were used to assess the relations between sleep characteristics and reproductive outcomes after adjusting for relevant confounders. We also performed stratified analyses by subjective sleep quality (good versus poor) and maternal age (≤30 versus >30 years). MAIN RESULTS AND THE ROLE OF CHANCE: Compared with women who slept 7 to <8 h/night, those who slept <7 h/night exhibited decreases in the number of retrieved and mature oocytes of 11.5% (95% CI: -21.3%, -0.48%) and 11.9% (95% CI: -22.4%, -0.03%), respectively. A mid-sleep time (MST) earlier than 2:21 a.m. (<2:21 a.m.) or later than 3:00 a.m. (≥3:00 a.m.) and poor subjective sleep quality were inversely associated with the fertilization rate. Women who had trouble falling asleep more than three times per week had a lower number of mature oocytes (-10.5%, 95% CI: -18.6%, -1.6%), normal fertilized oocytes (-14.8%, 95% CI: -23.7%, -4.8%) and good-quality embryos (-15.1%, 95% CI: -25.4%, -3.5%) than those who had no such trouble. In addition, women who slept 9 to <10 h/night had a lower chance of clinical pregnancy compared to women who slept 7 to <8 h/night (odds ratio = 0.65, 95% CI: 0.44, 0.98). In the stratified analyses, the positive associations of nocturnal sleep duration with the number of good-quality embryos and fertilization rate existed only among the women with poor subjective sleep quality (P for interaction = 0.02 and 0.03, respectively). Additionally, we found that the positive associations of nocturnal sleep duration with implantation or clinical pregnancy only existed among women aged over 30 years (P for interaction = 0.04 and 0.01, respectively). LIMITATIONS, REASONS FOR CAUTION: Sleep characteristics are self-reported, which may lead to misclassification. MST serves as a proxy of chronotype and may be non-differentially misclassified resulting in an underestimate of the association of interest. Measuring sleep characteristics on the day of oocyte retrieval may lead to bias. Chance findings cannot be excluded because of the limited number of women with <7 h or ≥10 h nocturnal sleep and multiple testing. Our results may be biased by other confounders and may not be generalizable to women of other ethnicities. WIDER IMPLICATIONS OF THE FINDINGS: Unhealthy sleep characteristics, including short nocturnal sleep, inappropriate sleep time, poor subjective sleep quality and having trouble falling asleep, may impair oocyte quantity and its potential to mature or be fertilized. Long nocturnal sleep might reduce the chance of clinical pregnancy among infertile females, especially women younger than 30 years old. Prolonged nocturnal sleep duration may be a potential beneficial behavior for improving IVF/ICSI outcomes for women aged over 30 years and women with poor subjective sleep quality, which requires further investigation. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Natural Science Foundation of China (81771654) and the National Key R&D Program of China (No. 2018YFC1004201). There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Structural Characterization and ORR Activity of a Copper Complex Borate and an Unexpected [Ni(atta)(SO4)0.5]+ Borate-Sulfate.

Two metal templated borates, [Ni(atta)(SO4)0.5]·[B5O6(OH)4] (1) and [Cu(1-MI)4]·[B5O6(OH)4]2·1-MI2 (2), have been synthesized. The structures were determined by single-crystal X-ray diffraction and further characterized by Fourier transform infrared (FTIR), elemental analysis, and powder X-ray diffraction (PXRD). The structure of 1 consists of [B5O6(OH)4]- clusters and [Ni(atta)(SO4)0.5]+ complexes, which shows a very rare Ni-O-S bond. 1 and 2 exhibit a hydrogen-bonded network formed by [B5O6(OH)4]- clusters. Oxygen reduction reaction (ORR) activities of 1 and 2 were explored.

Exposure to disinfection by-products and reproductive hormones among women: Results from the Tongji Reproductive and Environmental (TREE) study.

BACKGROUND: Disinfection by-products (DBPs) have been shown to impair female reproductive function. However, epidemiological evidence on reproductive hormones is scarce. OBJECTIVE: To investigate the associations between DBP exposures and reproductive hormones among women undergoing assisted reproductive technology. METHODS: We included 725 women from the Tongji Reproductive and Environmental (TREE) Study, an ongoing cohort conducted in Wuhan, China during December 2018 and January 2020. Urine samples collected at recruitment were quantified for dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) as biomarkers of DBP exposures. At day 2-5 of menstruation, serum reproductive hormones including luteinizing hormone (LH), estradiol (E2), total testosterone (T), progesterone (PRGE), and prolactin (PRL) were determined. Multivariate linear regression models were performed to assess the associations of urinary DCAA and TCAA concentrations with reproductive hormone levels. Dose-response relationships were investigated using natural cubic spline (NCS) and restricted cubic spline (RCS) models. RESULTS: After adjusting for relevant confounders, we observed that higher urinary DCAA levels were associated with increased serum PRGE (9.2%; 95% CI: -0.55%, 19.8% for the highest vs. lowest tertile; P for trend = 0.06). Based on NCS models, we observed U-shaped associations of urinary DCAA with serum PRGE and PRL; each ln-unit increment in urinary DCAA concentrations above 3.61 µg/L and 6.30 µg/L was associated with 18.9% (95% CI: 4.8%, 34.7%) and 23.3% (95% CI: -0.92%, 53.5%) increase in serum PRGE and PRL, respectively. The U-shaped associations were further confirmed in RCS models (P for overall association ≤0.01 and P for non-linear associations ≤0.04). We did not observe evidence of associations between urinary TCAA and reproductive hormones. CONCLUSION: Urinary DCAA but not TCAA was associated with altered serum PRGE and PRL levels among women undergoing assisted reproductive technology.

Urinary concentrations of phenols, oxidative stress biomarkers and thyroid cancer: Exploring associations and mediation effects.

Phenols have been shown to influence the cellular proliferation and function of thyroid in experimental models. However, few human studies have investigated the association between phenol exposure and thyroid cancer, and the underlying mechanisms are also poorly understood. We conducted a case-control study by age- and sex-matching 143 thyroid cancer and 224 controls to investigate the associations between phenol exposures and the risk of thyroid cancer, and further to explore the mediating role of oxidative stress. We found that elevated urinary triclosan (TCS), bisphenol A (BPA) and bisphenol S (BPS) levels were associated with increased risk of thyroid cancer (all P for trends < 0.05), and the adjusted odds ratios (ORs) comparing the extreme exposure groups were 3.52 (95% confidence interval (CI): 2.08, 5.95), 2.06 (95% CI: 1.06, 3.97) and 7.15 (95% CI: 3.12, 16.40), respectively. Positive associations were also observed between urinary TCS, BPA and BPS and three oxidative stress biomarkers measured by 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoPGF2α) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA), as well as between urinary 8-isoPGF2α and HNE-MA and the risk of thyroid cancer. Mediation analysis showed that urinary 8-isoPGF2α mediated 28.95%, 47.06% and 31.08% of the associations between TCS, BPA and BPS exposures and the risk of thyroid cancer, respectively (all P < 0.05). Our results suggest that exposure to TCS, BPA and BPS may be associated with increased risk of thyroid cancer and lipid peroxidation may be an intermediate mechanism. Further studies are warranted to confirm the findings.

Prenatal Exposure to Disinfection Byproducts and Intrauterine Growth in a Chinese Cohort.

Disinfection byproduct (DBP) exposure has been associated with birth size, pregnancy oxidative stress, and other adverse perinatal outcomes. However, little is known about the potential effect of prenatal DBP exposure on intrauterine growth. The present study included 1516 pregnant women from the Xiaogan Disinfection By-Products (XGDBP) birth cohort who were measured for four blood trihalomethanes [i.e., chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM)] and two urinary haloacetic acids [i.e., dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA)] across pregnancy trimesters. Second- and third-trimester fetal ultrasound measures of the abdominal circumference (AC), head circumference, biparietal diameter, femur length, and estimated fetal weight and birth weight were converted into z-scores. After adjusting for potential confounders, linear mixed models showed a decreasing AC z-score across tertiles of blood brominated THM (Br-THMs, the sum of BDCM, DBCM, and TBM) and total THM (THM4, the sum of Br-THMs and TCM) concentrations (both p for trend <0.01). We also observed a decreasing AC z-score across categories of blood TBM during pregnancy trimesters (p for trend = 0.03). Urinary haloacetic acids were unrelated to fetal growth parameters. In summary, prenatal exposure to THMs, particularly during the first trimester, was associated with reduced fetal abdominal circumference.

Urinary biomarker of strontium exposure is positively associated with semen quality among men from an infertility clinic.

Experimental studies have shown that nonradioactive strontium (Sr), in the form of Sr2+, have a positive effect on semen quality, but human evidence is lacking. This study aimed to examine the associations between nonradioactive Sr exposure and semen quality in Chinese men (n = 394). We recruited men who presented at an infertility clinic in Wuhan, China to seek for semen parameter analyses. Urinary Sr concentration as an exposure biomarker was measured using inductively coupled plasma mass spectrometer. We estimated the associations between urinary Sr concentrations and semen parameters using multivariable logistic and linear regression models. In multivariable linear regressions models, positive dose-response associations were estimated for sperm concentration, motility, and count across increasing urinary Sr quartiles (all p for trends<0.05), and the consistent positive associations were also observed for urinary Sr concentration modeled as a continuous exposure. In multivariable logistic models, decreased risks of below-reference sperm concentration, motility, and count were also estimated across increasing urinary Sr quartiles (all p for trends<0.05). Our results suggest that nonradioactive Sr exposure may have a beneficial effect on semen quality, but more investigations are warranted to confirm the results.

Urinary Biomarker of Prenatal Exposure to Disinfection Byproducts, Maternal Genetic Polymorphisms in CYP2E1 and GSTZ1, and Birth Outcomes.

The effects of disinfection byproducts (DBPs) on adverse birth outcomes remain unsettled. Maternal genetic variants in relation to DBP metabolism may modify this effect. Pregnant women during late pregnancy (n = 1306) were included from a Chinese cohort. Maternal urinary trichloroacetic acid (TCAA) was measured as a biomarker of DBP exposure. Maternal genotyping was conducted in cytochrome P450 2E1 (CYP2E1; rs2031920, rs3813867, and rs915906) and glutathione S-transferase zeta-1 (GSTZ1; rs7975). The associations between maternal urinary TCAA and birth outcomes and statistical interactions between maternal exposure and genetic polymorphisms were estimated. We found that maternal urinary TCAA levels were associated with decreased birth weight (P for trend = 0.003) and ponderal index (P for trend = 0.004). Interaction analyses showed that maternal urinary TCAA in association with decreased birth weight was observed only among subjects with CYP2E1 rs3813867 GC/CC versus GG (Pint = 0.07) and associations with decreased birth length, ponderal index, and gestational age were observed only among subjects with GSTZ1 rs7975 GA/AA versus GG (Pint = 0.07, 0.02, and 0.02, respectively). Our results suggested that prenatal DBP exposure was negatively associated with birth weight and ponderal index, and maternal genetic polymorphisms in CYP2E1 and GSTZ1 might modify these associations.

Urinary biomarker of late pregnancy exposure to drinking water disinfection by-products and ultrasound measures of fetal growth in Wuhan, China.

BACKGROUND: Disinfection by-products (DBPs) have been shown to be reproductive and developmental toxicity. However, few studies examine the effect of prenatal exposure to DBPs on fetal growth via ultrasound measures. OBJECTIVE: To investigate the associations between maternal exposure to DBPs during late pregnancy and ultrasound measures of fetal growth. METHODS: We included 332 pregnant women who presented to a hospital to wait for delivery in Wuhan, China. Ultrasound parameters of fetal growth including femur length (FL), head circumference (HC), abdominal circumference (AC) and biparietal diameter (BPD) were assessed. We measured maternal TCAA concentrations in first morning urine collected from late pregnancy as a biomarker of in utero DBP exposure levels. Multivariable linear regression models were used to examine the associations between maternal urinary TCAA concentrations during late pregnancy and ultrasound parameters of fetal growth. RESULTS: We found that elevated maternal creatinine (Cr)-adjusted urinary TCAA levels had negative associations with BPD, HC and FL in boys but not in girls (P interaction = 0.04, 0.05 and 0.08, respectively). Male fetal BPD, HC and FL had decreases of 0.21 cm (95% CI: -0.35, -0.07; P for trend = 0.003), 0.46 cm (95% CI: -0.81, -0.10; P for trend = 0.01) and 0.17 cm (95% CI: -0.30, -0.04; P for trend = 0.01) for the highest vs. lowest tertile of Cr-adjusted urinary TCAA, respectively. These negative associations persisted for maternal Cr-adjusted urinary TCAA concentrations modeled as continuous variables. CONCLUSION: The results from our study suggest that maternal exposure to TCAA during late pregnancy may have adverse effects on male fetal growth.

Mediation of the relationship between phthalate exposure and semen quality by oxidative stress among 1034 reproductive-aged Chinese men.

BACKGROUND: Emerging evidence from animals indicates that oxidative stress plays a crucial role in the effects of phthalate exposure on male reproductive dysfunctions, which has never been thoroughly explored in humans. OBJECTIVE: To explore the potential mediating role of oxidative stress in the association of phthalate exposure with semen quality among 1034 Chinese men. METHOD: Repeated urine samples gathered from the male partners of sub-fertile couples were analyzed for 3 oxidative stress markers [8-hydroxy-2-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoPGF2α) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)], using a liquid chromatography-tandem mass spectrometry. Multivariate regression models were constructed to evaluate the associations of urinary oxidative stress markers with urinary phthalate metabolites and semen quality. We also explored the potential mediation effects by oxidative stress markers. RESULTS: Significantly positive dose-dependent relationships were observed between each individual phthalate metabolite and all analyzed oxidative stress markers (all p for trend<0.05), except for monoethyl phthalate (MEP) in relation to HNE-MA. Additionally, significantly or suggestively inverse dose-dependent relationships were exhibited between urinary 8-isoPGF2α and sperm concentration (p for trend = 0.05), and between urinary 8-OHdG and percent of normal sperm morphology (p for trend = 0.01). Mediation analysis showed that urinary 8-isoPGF2α suggestively mediated 12% of the inverse association between monobutyl phthalate (MBP) and sperm concentration, and that urinary 8-OHdG suggestively mediated 32% of the inverse association of MEP with percent of normal sperm morphology (both p < 0.10). CONCLUSIONS: Although further investigations are required, our results suggest that oxidative stress may play a mediating role in the effects of phthalate exposure on impaired semen quality.

Novel application of imidazole-based ligand-templated borates in a zinc-air battery.

Two templated borates, [Co(1-EI)2]·[B5O7(OH)3] (1) and [Ga(1-MI)2·B6O9(OH)4]·[H3BO3]·H[1-MI] (2), have been synthesized using a mild method. Notably, they exhibit an excellent ORR performance with an E1/2 value of 0.84 V and are the first to be used as the positive electrode catalyst for a zinc-air battery, which opens a pathway for the application of borate-based oxide catalysts.

Metabolomic Analysis Reveals Association between Decreased Ovarian Reserve and In Vitro Fertilization Outcomes.

In vitro fertilization (IVF) is a highly effective treatment for infertility; however, it poses challenges for women with decreased ovarian reserve (DOR). Despite the importance of understanding the impact of DOR on IVF outcomes, limited research has explored this relationship, particularly using omics approaches. Hence, we conducted a study to investigate the association between DOR and IVF outcomes, employing a metabolomic approach. We analyzed serum samples from 207 women undergoing IVF treatment, including 89 with DOR and 118 with normal ovarian reserve (NOR). Our findings revealed that DOR was significantly associated with unfavorable IVF outcomes, characterized by a reduced oocyte count, lower embryo quality, and decreased rates of pregnancy and live births. Furthermore, we identified 82 metabolites that displayed significant alterations in DOR patients, impacting diverse metabolic pathways. Notably, a distinct panel of metabolites, including palmitic acid, stearic acid, LysoPC(9:0(CHO)/0:0), PC(18:0/9:0(CHO)), and PC(16:0/9:0(CHO)), exhibited discriminatory power between the DOR and NOR groups, showcasing a strong correlation with IVF outcomes. These findings emphasize the crucial role of metabolomic disruptions in influencing IVF outcomes among women with DOR.

Self-Rated Health and Semen Quality in Men Undergoing Assisted Reproductive Technology.

Importance: Numerous studies have documented the association of self-rated health (SRH) with chronic diseases. However, few studies have investigated its association with semen quality. Objective: To examine the association of SRH with semen quality among men undergoing assisted reproductive technology (ART) in China. Design, Setting, and Participants: This cross-sectional study recruited male partners in couples undergoing ART treatment at the Center for Reproductive Medicine, Tongji Hospital, Wuhan, China. A total of 1262 men underwent 2 semen examinations and completed a questionnaire on SRH between December 2018 and January 2020. Data analysis was performed from November 20, 2022, to March 24, 2023. Exposure: SRH, including overall physical and mental health, as well as reproductive-related physical and mental health specifically, were reported at baseline recruitment. Main Outcomes and Measures: Sperm concentration, sperm progressive motility, sperm motility, and sperm count as semen quality parameters. Results: The study included 1262 men with a mean (SD) age of 32.79 (5.25) years and body mass index of 24.37 (3.68). Men with poorer SRH had lower semen quality (eg, sperm concentration among poor vs very good overall physical health: percentage variation, -14.67%; 95% CI, -23.62% to -4.66%). Among 4 components of SRH, a greater reduction in semen quality was estimated for reproductive-related SRH compared with overall SRH, whereas the greatest reduction was observed for reproductive-related physical SRH. In comparison with men with very good reproductive-related physical SRH, men with poor reproductive-related physical SRH had differences of -24.78% (95% CI, -32.71% to -15.93%) and -25.61% (95% CI, -33.95% to -16.22%) in sperm count and concentration, respectively, and regression coefficients of -9.38 (95% CI, -12.01 to -6.76) and -9.24 (95% CI, -11.82 to -6.66) for sperm motility and sperm progressive motility, respectively. Conclusions and Relevance: In this cross-sectional study of Chinese men, poorer SRH was associated with lower semen quality, and reproductive-related physical SRH was the most pronounced indicator. Our findings suggest that SRH, especially reproductive-related physical SRH, was a good indicator of semen quality, which should inform public and clinical regulatory decisions.

Association between Urinary Haloacetic Acid Concentrations and Liver Injury among Women: Results from the Tongji Reproductive and Environmental (TREE) Study.

BACKGROUND: Experimental studies have shown that disinfection byproducts (DBPs) including haloacetic acids (HAAs) can cause liver toxicity, but evidence linking this association in humans is sparse. OBJECTIVES: We aimed to explore the associations between HAA exposures and liver injury. METHODS: We included 922 women between December 2018 and January 2020 from the Tongji Reproductive and Environmental (TREE) cohort study in Wuhan, China. Urinary HAA concentrations including trichloroacetic acid (TCAA) and dichloroacetic acid (DCAA) and serum indicators of liver function, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT) were measured. Liver injury was defined as if any of serum indicator levels were above the 90th percentile. Multivariate logistic and linear regression models were fitted to assess the associations of urinary HAA concentrations with the risk of liver injury and liver function indicators. Stratified analyses by age, body mass index (BMI), alcohol use, and passive smoking were also applied to evaluate the potential effect modifiers. RESULTS: There is little evidence of associations of urinary TCAA concentrations with liver injury risk and liver function indicators. However, urinary DCAA concentrations were associated with a higher risk of liver injury [odds ratios (OR) for 1-interquartile range (IQR) increase in natural log (ln) transformed DCAA concentrations: 1.45; 95% confidence interval (CI): 1.07, 1.98]. This association was observed only among nondrinkers (pinteraction=0.058). We also found that a 1-IQR increase in ln-transformed DCAA concentrations was positively associated with ALT levels (percentage change=6.06%; 95% CI: 0.48%, 11.95%) and negatively associated with AST/ALT (percentage change=-4.48%; 95% CI: -7.80%, -1.04%). In addition, urinary DCAA concentrations in relation to higher GGT levels was observed only among passive smokers (pinteraction=0.040). CONCLUSION: Our findings suggest that exposure to DCAA but not TCAA is associated with liver injury among women undergoing assisted reproductive technology. https://doi.org/10.1289/EHP13386.

Prenatal exposures to phthalates and bisphenols in relation to oxidative stress: single pollutant and mixtures analyses.

Prenatal exposures to phthalates and bisphenols have been shown to be linked with adverse birth outcomes. Oxidative stress (OS) is considered a potential mechanism. The objective of this study was to explore the individual and mixtures of prenatal exposures to phthalates and bisphenols in associations with OS biomarkers. We measured eight phthalate metabolites and three bisphenols in the urine samples from 105 pregnant women in Wuhan, China. Urinary 8-hydroxydeoxyguanosine (8-OHdG), 8-isoprostaglandin F2α (8-isoPGF2α), and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA) were determined as OS biomarkers. The OS biomarkers in associations with the individual chemicals were estimated by linear regression models and restricted cubic spline (RCS) models, and their associations with the chemical mixtures were explored by quantile g-computation (qg-comp) models. In single-pollutant analyses, five phthalate metabolites including monomethyl phthalate (MMP), monoethyl phthalate (MEP), mono-(2-ethylhexyl) phthalate (MEHP), (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) were positively associated with urinary 8-OHdG levels (all FDR-adjusted P = 0.06). These associations were further confirmed by the RCS models and were linear (P for overall association ≤ 0.05 and P for non-linear association > 0.05). In mixture analyses, qg-comp models showed that a one-quartile increase in the chemical mixtures of phthalate metabolites and bisphenols was positively associated with urinary levels of 8-OHdG and 8-isoPGF2α, and bisphenol A (BPA) and bisphenol F (BPF) were the most contributing chemicals, respectively. Prenatal exposures to individual phthalates and mixtures of phthalates and bisphenols were associated with higher OS levels.

Urinary haloacetic acid concentrations and thyroid function among women: Results from the TREE study.

BACKGROUND: Disinfection byproducts (DBPs) have been shown to impair thyroid function in experimental models. However, epidemiological evidence is scarce. METHODS: This study included 1190 women undergoing assisted reproductive technology (ART) treatment from the Tongji Reproductive and Environmental (TREE) cohort from December 2018 to August 2021. Serum thyrotropin (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were measured as indicators of thyroid function. FT4/FT3 and TSH/FT4 ratios were calculated as markers of thyroid hormone homeostasis. Dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA), the two most abundant HAAs, in urine were detected to assess individual DBP exposures. RESULTS: After adjusting for relevant covariates, positive associations were observed between urinary TCAA concentrations and serum TSH and TSH/FT4 levels (e.g., percent change = 5.82 %, 95 % CI: 0.70 %, 11.21 % for TSH), whereas inverse associations were found for serum FT3 and FT4 (e.g., percent change = -1.29 %, 95 % CI: -2.49 %, -0.07 % for FT3). There also was a negative association between urinary DCAA concentration and serum FT4/FT3 (percent change = -2.49 %, 95 % CI: -4.71 %, -0.23 %). These associations were further confirmed in the restricted cubic spline and generalized additive models with linear or U-shaped dose-response relationships. CONCLUSION: Urinary HAAs were associated with altered thyroid hormone homeostasis among women undergoing ART treatment.

Urinary biomarkers of drinking-water disinfection byproducts in relation to diminished ovarian reserve risk: A case-control study from the TREE cohort.

BACKGROUND: Disinfection byproducts (DBPs) as ovarian toxicants have been documented in toxicological studies. However, no human studies have explored the effects of exposure to DBPs on diminished ovarian reserve (DOR). OBJECTIVE: To assess whether urinary biomarkers of exposure to drinking-water DBPs were associated with DOR risk. METHODS: A total of 311 women undergoing assisted reproductive technology were diagnosed with DOR in the Tongji Reproductive and Environmental (TREE) cohort from December 2018 to August 2021. The cases were matched to the controls with normal ovarian reserve function by age in a ratio of 1:1. Urinary trichloroacetic acid (TCAA) and dichloroacetic acid (DCAA) were quantified as biomarkers of drinking-water DBP exposures. The conditional logistic regression and restricted cubic spline (RCS) were used to explore urinary biomarkers of drinking-water DBP exposures in associations with the risk of DOR. RESULTS: Elevated urinary DCAA levels were associated with higher DOR risk [adjusted odds ratio (OR) = 1.87; 95 % confidence interval (CI): 1.16, 3.03 for the highest vs. lowest quartiles; P for trend = 0.016]. The association was confirmed in the RCS model, with a linear dose-response curve (P for overall association = 0.029 and P for non-linear association = 0.708). The subgroup analysis by age and body mass index (BMI) showed that urinary DCAA in association with DOR risk was observed among women ≥35 years old and leaner women (BMI < 24 kg/m2), but the group differences were not statistically significant. Moreover, a U-shaped dose-response curve between urinary TCAA and DOR risk was estimated in the RCS model (P for overall association = 0.011 and P for non-linear association = 0.004). CONCLUSIONS: Exposure to drinking-water DBPs may contribute to the risk of DOR among women undergoing assisted reproductive technology.