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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. [ABSTRACT FROM AUTHOR]

• Exposures to BPA analogues in associations with serum hormones were examined. • Higher BPF and BPS exposures were associated with lower E2 levels and E2/T ratio. • Higher BPS exposure was associated with lower SHBG levels. • Age and BMI had modifying effects on these associations. Bisphenol A (BPA) as an endocrine disrupting chemical has been shown to alter reproductive endocrine function, but little is known on its analogues such as bisphenol F (BPF) and bisphenol S (BPS) with increasing usage and exposure. To explore the associations between exposures to BPA, BPF and BPS and serum reproductive hormones among reproductive-aged Chinese men. We measured BPA, BPF and BPS concentrations in repeated urine samples and multiple reproductive hormones in the serum samples collected from 462 men attending an infertility clinic in Wuhan, China. Linear regression models were applied to assess the associations between averaged urinary BPA, BPF and BPS levels and serum hormone concentrations, and restricted cubic spline (RCS) models were further utilized to explore potential non-linear associations. We also examined potential modifying effects by age and body mass index (BMI). There was little evidence of associations between BPA exposure and altered reproductive hormones. However, we found that elevated BPF and BPS exposures were in negative associations with estrogen (E2) levels and E2/T (total testosterone) ratio (all P for trends < 0.05), and that elevated BPS exposure was negatively associated with SHBG levels (P for trend = 0.09). Based on the RCS models, these linear negative associations except that between BPS exposure and E2/T ratio were further confirmed. In stratified analyses, BPF and BPS exposures in relation to reduced E2 and E2/T ratio were more pronounced among men aged > 30 years, whereas their associations with reduced SHBG levels were more pronounced among men aged ≤ 30. Also, BPS exposure in negative association with FSH only emerged among men with BMI ≥ 24 kg/m2 (P for interaction = 0.03). BPF and BPS exposures were negatively associated with male serum E2, E2/T ratio and SHBG levels, and these associations varied by age and BMI. [ABSTRACT FROM AUTHOR]

Organochlorine pesticides (OCPs) are endocrine-disrupting chemicals and may alter male reproductive hormone concentrations. To explore the associations between multiple OCP exposures and serum testosterone concentrations among Chinese men. We investigated 421 men who provided serum samples from an infertility clinic in Wuhan, China. Each man completed a questionnaire concerning demographic characteristics and lifestyle habits. Serum concentrations of 18 OCPs and total testosterone were measured. Linear regression models were used to explore whether serum OCP levels were associated with altered testosterone concentrations, and potential effect modifications by age and body mass index (BMI) were also examined. After adjusting for potential confounders, elevated dieldrin and p,p'-DDD levels had monotonically negative and positive exposure-response associations with testosterone concentrations, respectively (−30.98 ng/dL, 95% CI: −72.34, 10.37; P for trend = 0.12 and 41.31 ng/dL, 95% CI: −0.32, 82.93; P for trend = 0.06 for the highest vs. non-detectable exposure category, respectively). After stratification by age and BMI, dieldrin in relation to decreased testosterone concentrations was more pronounced among men aged <30 years old, and p,p'-DDD in relation to increased testosterone concentrations was stronger among men aged ≥30 years old and among men with a BMI <24 kg/m2, though the differences were not statistically significant. The study found evidence that serum dieldrin and p,p'-DDD concentrations might be associated with altered serum testosterone concentrations. [Display omitted] • Multiple organochlorine pesticides in relation to testosterone among men were assessed. • Dieldrin was negatively associated with serum testosterone concentrations. • p,p′-DDD was positively associated with serum testosterone concentrations. • Age and BMI might modify the magnitude of these associations. [ABSTRACT FROM AUTHOR]

Disinfection by-products (DBPs) have been shown to impair female reproductive function. However, epidemiological evidence on reproductive hormones is scarce. To investigate the associations between DBP exposures and reproductive hormones among women undergoing assisted reproductive technology. 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 (E 2), 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. 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. Urinary DCAA but not TCAA was associated with altered serum PRGE and PRL levels among women undergoing assisted reproductive technology. • We included 725 women from the TREE cohort. • Urinary TCAA and DCAA were used as disinfection by-product exposure biomarkers. • Serum reproductive hormones were determined on day 2–5 of menstruation. • We found U-shaped associations between DCAA and serum progesterone and prolactin. • The threshold DCAA concentrations were 3.61 μg/L and 6.30 μg/L, respectively. [ABSTRACT FROM AUTHOR]

Disinfection byproducts (DBPs) have been shown to alter ovarian steroidogenesis and cause estrous cyclicity disturbance and prolongation in experimental studies, however human studies are lacking. We aimed to evaluate the cross-sectional associations between drinking water DBPs and menstrual cycle characteristics. A total of 1078 women attending an infertility clinic in Wuhan, China were included between December 2018 and January 2020. Characteristics of menstrual cycle were collected by questionnaires. Concentrations of dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) were measured in urine as biomarkers of drinking water DBPs. Multivariate logistic and linear regression models were used to evaluate the associations between urinary DCAA and TCAA concentrations and menstrual cycle characteristics. Higher urinary DCAA concentrations were associated with increased odds ratios (ORs) of irregular menstrual cycle (OR = 1.80; 95% CI: 0.97, 3.33 for the highest vs. lowest quartile; P for trend = 0.05) and long menstrual cycle (OR = 1.62; 95% CI: 0.97, 2.70 for the highest vs. lowest quartile; P for trend = 0.06), as well as prolonged variation in cycle length (β = 1.27 days; 95% CI: -0.11, 2.66 for the highest vs. lowest quartile; P for trend = 0.04). Higher urinary TCAA concentrations were associated with prolonged bleeding duration (β = 0.23 days; 95% CI: -0.06, 0.51 for the highest vs. lowest quartile; P for trend = 0.07). These results suggest that exposure to drinking water DBPs is associated with menstrual cycle disturbances. These findings are warranted to confirm in other studies. [ABSTRACT FROM AUTHOR]

Experimental studies have demonstrated that disinfection byproducts (DBPs) can cause ovarian toxicity including inhibition of antral follicle growth and disruption of steroidogenesis, but there is a paucity of human evidence. We aimed to investigate whether urinary biomarkers of exposure to drinking water DBPs were associated with ovarian reserve. The present study included 956 women attending an infertility clinic in Wuhan, China from December 2018 to January 2020. Antral follicle count (AFC), ovarian volume (OV), anti-Mullerian hormone (AMH), and follicle-stimulating hormone (FSH) were measured as indicators of ovarian reserve. Urinary dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) were assessed as potential biomarkers of drinking water DBP exposures. Multivariate linear and Poisson regression models were applied to estimate the associations of urinary DCAA and TCAA concentrations with indicators of ovarian reserve. Elevated urinary DCAA and TCAA levels were monotonically associated with reduced total AFC (− 5.98%; 95% CI: − 10.30%, − 1.44% in DCAA and − 12.98%; 95% CI: − 17.00%, − 8.76% in TCAA comparing the extreme tertiles; both P for trends ≤ 0.01), and the former was only observed in right AFC but not in left AFC, whereas the latter was estimated for both right and left AFC. Moreover, elevated urinary TCAA levels were monotonically associated with decreased AMH (− 14.09%; 95% CI: − 24.79%, − 1.86% comparing the extreme tertiles; P for trend = 0.03). These negative associations were still observed for the exposure biomarkers modeled as continuous variables. Our findings suggest that exposure to drinking water DBPs may be associated with decreased ovarian reserve. [Display omitted] ● The effects of DBP exposures on ovarian reserve were firstly evaluated in humans. ● Urinary DCAA and TCAA were measured as biomarkers of DBP exposures. ● Urinary TCAA was associated with reduced AFC and AMH. ● Urinary DCAA was associated with decreased right AFC. [ABSTRACT FROM AUTHOR]