Association of severity of menstrual dysfunction with cardiometabolic risk markers among women with polycystic ovary syndrome.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is associated with a wide range of unfavorable cardiometabolic risk factors, including obesity, hypertension, insulin resistance, impaired glucose metabolism, dyslipidemia, and metabolic syndrome. Compared with women with regular menstrual cycles, women with a history of irregular menstrual periods have an increased unfavorable cardiometabolic risk. Recently, the association between the severity of oligomenorrhea and hyperinsulinemia and insulin resistance has been demonstrated. However, evidence linking the severity of menstrual cyclicity with cardiometabolic risk in PCOS women is scarce. MATERIAL AND METHODS: This work was a prospective cross-sectional study. A total of 154 women diagnosed with PCOS by the Rotterdam criteria were recruited from July 2021 to September 2022. PCOS women with eumenorrheic (eumeno group), oligomenorrhea (oligo group), and amenorrhea (ameno group) underwent history and physical examination, gonadal steroid hormone measurement, lipid profile, oral glucose tolerance test, and homeostasis model assessment of insulin resistance. RESULTS: A trend toward an increase in unfavorable cardiometabolic risk markers including obesity, hypertension, prevalence of insulin resistance, prediabetes, dyslipidemia, and metabolic syndrome was observed in the ameno group (n = 57) as compared with the eumeno (n = 24) or oligo group (n = 73). A higher prevalence of insulin resistance (odds ratio [OR]: 3.02; 95% confidence interval [CI]: 1.03-8.81) and prediabetes (OR: 3.94; 95% CI: 1.01-15.40) was observed in the ameno group than in the eumeno group, and a higher proportion of dyslipidemia (OR: 2.44; 95% CI: 1.16-5.15) was observed in the ameno group than in the oligo group in the binary logistic regression analysis after adjusting for confounding factors. CONCLUSIONS: PCOS women with amenorrhea show a higher prevalence of insulin resistance, prediabetes, and dyslipidemia compared with those with oligomenorrhea or eumenorrhea. The severity of menstrual dysfunction could be used as a readily obtainable marker for the identification of PCOS women at greatest risk of cardiometabolic diseases.

Co-exposure to 55 endocrine-disrupting chemicals linking diminished sperm quality: Mixture effect, and the role of seminal plasma docosapentaenoic acid.

Isolated effects of single endocrine-disrupting chemicals (EDCs) on male reproductive health have been studied extensively, but their mixture effect remains unelucidated. Previous research has suggested that consuming diet enriched in omega-3 polyunsaturated fatty acids (PUFA) might be beneficial for reproductive health, whether omega-3 PUFA could moderate the effect of EDCs mixture on semen quality remains to be explored. In this study of 155 male recruited from a reproductive health center in China, we used targeted-exposomics to simultaneously measure 55 EDCs in the urine for exposure burden. Regression analyses were restricted to highly detected EDCs (≥55%, n = 34), and those with consistently elevated risk were further screened and brought into mixture effect models (Bisphenol A, ethyl paraben, methyl paraben [MeP], benzophenone-1 [BP1], benzophenone-3, mono(3-carboxypropyl) phthalate [MCPP]). Bayesian Kernel Machine Regression (BKMR) and quantile-based g-computation (QGC) models demonstrated that co-exposure to top-ranked EDCs was related to reduced sperm total (ß = -0.18, 95%CI: -0.29 - -0.07, P = 0.002) and progressive motility (ß = -0.27, 95%CI: -0.43 - -0.10, P = 0.002), but not to lower semen volume. BP1, MeP and MCPP were identified as the main effect driver for deteriorated sperm motion parameters using mixture model analyses. Seminal plasma fatty acid profiling showed that high omega-3 PUFA status, notably elevated docosapentaenoic acid (DPA, C22:5n-3) status, moderated the association between MCPP and sperm motion parameters (total motility: ß = 0.26, 95%CI: 0.01 - -0.51, Pinteraction = 0.047; progressive motility: ß = 0.64, 95%CI: 0.23 - 1.05, Pinteraction = 0.003). Co-exposure to a range of EDCs is mainly associated with deteriorated sperm quality, but to a lesser extent on sperm quantity, high seminal plasma DPA status might be protective against the effect. Our work emphasizes the importance of exposomic approach to assess chemical exposures and highlighted a new possible intervention target for mitigating the potential adverse effect of EDCs on semen quality.

"Cocktail" of environmental chemicals and early reproductive outcomes of IVF: The insight from paternal and maternal exposure.

BACKGROUND: Humans are exposed to various chemicals, including organophosphate esters (OPEs), phthalates (PAEs), and phenols. The effects on early reproductive outcomes of in vitro fertilization (IVF) remain unclear. METHODS: We recruited 192 women and 157 men who underwent IVF treatment. A total of forty-nine urinary chemicals were detected, including six OPEs, fifteen PAEs, six parabens, two chlorophenols, nine bisphenols, five benzophenones, and six synthetic phenolic antioxidants. We examined the individual and joint effects of parental chemical exposure on early reproductive outcomes. RESULTS: We found that certain chemicals were associated with early reproductive outcomes in Poisson regression models. For example, urinary diphenyl phosphate was negatively associated with high-quality embryos in both female (ß: -0.12, 95%CI: -0.17, -0.07) and male partners (ß: -0.09, 95%CI: -0.15, -0.03). A negative association was found between mixed chemicals and high-quality embryos in Bayesian kernel machine regression, weighted quantile sum regression (ß: -0.34, 95%CI: -0.60, -0.07), and quantile-based g-computation model (ß: -0.69, 95%CI: -1.34, -0.05) among female partners. Paternal mixture exposure was not associated with early reproductive outcomes. CONCLUSIONS: Our results indicated that increased exposure to environmental chemicals was associated with adverse early reproductive outcomes of IVF, especially female partners.

Exposure to per- and polyfluoroalkyl substances in women with twin pregnancies: Patterns and variability, transplacental transfer, and predictors.

The extensive exposure to per- and polyfluoroalkyl substances (PFASs) has raised public health concerns. The issue of PFAS exposures in women with twin pregnancies remains unresolved. To determine exposure profiles, the transplacental transfer efficiencies (TTEs) of PFASs and predictors were estimated. We found that serum PFASs were widely detected, with detection rates of over 50% for 12 PFASs in maternal serum throughout pregnancy. The majority of PFAS levels exhibited fair to good reproducibility (ICCs > 0.40). Moderate to low correlations were observed for most PFASs between twin cord serum and maternal serum at three trimesters (rs = 0.13-0.77, p values < 0.01). We first presented a U-shaped trend for TTEs with increasing chain length for perfluoroalkyl carboxylic acids (PFCAs) and perfluoroalkyl sulfonic acids (PFSAs) in twins, even in twin sex subgroups. Further, we found that PC4 and PC5 (indicators of exposure to PFHxS and 6:2 Cl-PFESA) were positively associated with age (ß = 0.85, 1.30, and 1.36, respectively). Our findings suggested that there is moderate variability among certain PFASs and that these PFASs have the ability to cross the placental barrier. Exposure patterns were found to be associated with maternal age.

Long-Term Exposure to Ambient PM2.5 and Age-Related Cataracts among Chinese Middle-Aged and Older Adults: Evidence from Two National Cohort Studies.

Cataract is one key cause of visual disability and blindness. Ambient particulate matter is more likely to increase cataract risk due to eye continuous exposure to the environment. However, less is known about whether long-term exposure to particulate matter 2.5 (PM2.5) is related to age-related cataracts. We conducted a population-based study among 22,298 adults from two multicenter cohort studies [China Family Panel Studies (CFPS) and Chinese Longitudinal Healthy Longevity Survey (CLHLS)]. The associations between PM2.5 and age-related cataracts were analyzed by Cox proportional hazard regression models, which were also stratified according to demographic characteristics. The restricted cubic spline (RCS) model was used to explore the dose-response relationships between PM2.5 and age-related cataracts. The population attributable fraction (PAF) was calculated to assess the burden of age-related cataracts that can be attributed to PM2.5. In the final analysis, 1897 participants reported age-related cataracts during follow-up. Long-term exposure to PM2.5 was associated with age-related cataracts, with HRs of 1.165 (1.130, 1.201), 1.138 (1.103, 1.173), and 1.091 (1.057, 1.126) for per 10 µg/m3 increase at one-, two-, and three-year before the end of follow-up, respectively. Furthermore, associations between PM2.5 and age-related cataracts were also demonstrated in RCS models. The PAF of age-related cataracts to PM2.5 in the total participants was 24.63%. Our research found that long-term exposure to PM2.5 may increase the risk of age-related cataracts, and age-related cataracts should be considered as an important public health issue due to air pollution.

Phthalate exposure with sperm quality among healthy Chinese male adults: The role of sperm cellular function.

Adverse male reproduction caused by phthalate ester (PAE) exposure has been well documented in vivo. However, existing evidence from population studies remains inadequate to demonstrate the impact of PAE exposure on spermatogenesis and underlying mechanisms. Our present study aimed to explore the potential link between PAE exposure and sperm quality and the possible mediation by sperm mitochondrial and telomere in healthy male adults recruited from the Hubei Province Human Sperm Bank, China. Nine PAEs were determined in one pooled urine sample prepared from multiple collections during the spermatogenesis period from the same participant. Sperm telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) were determined in sperm samples. The sperm concentration and count per quartile increment in mixture concentrations were -4.10 million/mL (-7.12, -1.08) and -13.52% (-21.62%, -4.59%), respectively. We found one quartile increase in PAE mixture concentrations to be marginally associated with sperm mtDNAcn (ß = 0.09, 95% CI: -0.01, 0.19). Mediation analysis showed that sperm mtDNAcn significantly explained 24.6% and 32.5% of the relationships of mono-2-ethylhexyl phthalate (MEHP) with sperm concentration and sperm count (ß = -0.44 million/mL, 95% CI: -0.82, -0.08; ß = -1.35, 95% CI: -2.54, -0.26, respectively). Our study provided a novel insight into the mixed effect of PAEs on adverse semen quality and the potential mediation role of sperm mtDNAcn.

Co-exposure to phenols and phthalates during pregnancy with the difference of body size in twins at one month old.

Humans are simultaneously exposed to phenols and phthalates (PAEs). However, the mixture effect of phenols and PAEs on the body size of twins is lacking. From 2016 to 2018, we recruited 228 pregnant twins and collected up to three urine samples. A total of 8 PAE metabolites and 7 phenols were detected in urine by liquid chromatography-tandem mass spectrometry. Chemical individual and mixture effects were estimated. Multivariable linear regression results presented the percentage change in twins' growth differences at one month old with maternal PAE and phenol exposure. These chemicals were positively associated with weight differences during the entire trimester. Moreover, the quantile g-computed model showed that increased urinary concentrations of all chemicals by one quartile were associated with a 22.85% (95%CI: 11.21-35.72%), 22.60% (95%CI: 12.31-33.83%), and 24.05% (95%CI: 13.11-36.05%) larger weight difference within twins in each trimester, respectively. Increasing all PAE metabolites and phenols by one quantile across the entire trimester, weight differences increased by 26.61% (95% CI: 15.79%, 38.44%), and height differences increased by 15.84% (95%CI: 3.92%, 29.13%). Co-exposure to PAEs and phenols may primarily play a role in twins' growth.

Risk of thyroid cancer and benign nodules associated with exposure to parabens among Chinese adults in Wuhan, China.

Parabens are widely used as preservatives, which have been found to affect thyroid function in toxicological studies. However, population studies on whether they are associated with thyroid tumors remain unclear. This study aims to investigate the relationship between environmental paraben exposure and thyroid cancer and benign nodules. We recruited participants from the Department of Thyroid and Breast Surgery at Wuhan Central Hospital, Wuhan, China. The detectable percentages of methyl paraben, ethyl paraben, and propyl paraben in the urinary samples of 425 study subjects were 99.1%, 95.3%, and 92.0%, respectively. All uncorrected and creatinine-corrected parabens were moderately correlated with one another. After adjusting for possible confounders, all three parabens were associated with an increased risk of thyroid cancer. Furthermore, the mixture pollutant analysis of parabens found positive associations with risk of thyroid cancer (OR = 0.24, 95% CI: 0.18, 0.31) and benign nodules (OR = 1.33, 95% CI: 0.86, 1.80). We observed that individual exposure to paraben mixtures may be associated with the risk of thyroid cancer and benign nodules.

The Association of Certain Seminal Phthalate Metabolites on Spermatozoa Apoptosis: An Exploratory Mediation Analysis via Sperm Protamine.

Earlier studies have suggested that exposure to phthalates (PAEs) may induce spermatozoa apoptosis. Sperm protamine as a molecular biomarker during spermatozoa apoptotic processes may mediate the association between PAE exposure and spermatozoa apoptosis. This study aimed to explore whether sperm protamine mediates the association of PAE exposure with spermatozoa apoptosis. We determined sperm protamine levels, 8 PAE metabolite concentrations in seminal plasma, and 3 spermatozoa apoptosis parameters among 111 men from an infertility clinic. The associations of PAEs as individual chemicals and mixtures with sperm protamine were determined. The mediating roles of protamine in the associations between PAEs and spermatozoa apoptosis parameters were examined by mediation analysis. After adjusting for confounders, we observed positive correlations between seminal plasma concentrations of mono(2-ethylhexyl) phthalate (MEHP) and sperm protamine-1 and protamine ratio. Estimates comparing highest vs. lowest quartiles of MEHP concentration were 4.65% (95% CI: 1.47%, 7.82%) for protamine-1 and 25.86% (95% CI: 3.05%, 53.73%) for protamine ratio. The quantile g-computation models showed that the adjusted protamine-1 per quartile increase in PAE mixture was 9.42% (95% CI: 1.00, 20.92) with MEHP being the major contributor. Although the joint association between PAE mixture and protamine ratio was negligible, MEHP was still identified as the main contributor. Furthermore, we found that protamine-2 and protamine ratio levels in the highest quartiles exhibited a decrease of 43.45% (95% CI: 60.54%, -19.75%) and an increase of 122.55% (95% CI: 60.00%, 209.57%) in Annexin V+/PI- spermatozoa relative to the lowest quartiles, respectively. Mediation analysis revealed that protamine ratio significantly mediated 55.6% of the association between MEHP and Annexin V+/PI- spermatozoa elevation (5.13%; 95% CI: 0.04%, 10.52%). Our findings provided evidence that human exposure to PAEs was associated with increased protamine levels which may mediate the process of spermatozoa apoptosis.

Arsenic transfer along the soil-sclerotium-stroma chain in Chinese cordyceps and the related health risk assessment.

BACKGROUND: Chinese cordyceps (Lepidoptera: Ophiocordyceps sinensis)is a larval-fungus complex. The concentration and distribution of arsenic (As) may vary during the stroma (ST) germination process and between the sclerotium (SC) and the ST. The soil-to-Chinese cordyceps system is an environmental arsenic exposure pathway for humans. We studied the As concentration in the soil, the SC, and the ST of Chinese cordyceps, and performed a risk assessment. METHODS: Soil and Chinese cordyceps samples were collected from the Tibetan Plateau in China. The samples were analyzed for the total As concentration and As species determination, which were conducted by inductively coupled plasma mass spectrometry (ICP-MS) and HPLC-ICP-MS, respectively. RESULTS: The concentration of total As in the soil was much higher than in SC and ST. The major As species in the soil was inorganic AsV. In SC and ST, organic As was predominant, and the majority of As was an unknown organic form. There are significant differences in the As distribution and composition in soil, SC, and ST. Our risk assessment indicated that chronic daily ingestion was higher than inhalation and dermal exposure in children and adults. The hazard index (HI) of the non-carcinogenic and cancer risks (CR) for human health were HI ≤ 1 and CR < 1 × 10-4, respectively. CONCLUSION: The Chinese cordyceps possesses highly-efficient detoxifying characteristics and has a significant role in As transformation during its life cycle. We found that the levels of As in soils from the habitat of Chinese cordyceps were higher than the soil background values in China, but the probability for incurring health risks remained within the acceptable levels for humans.

Determination of arsenicals in mouse tissues after simulated exposure to arsenic from rice for sixteen weeks and the effects on histopathological features.

The accumulation of arsenic in rice has become a worldwide concern. In this study, dose-dependency in tissues (intestine, liver and kidney) and blood distribution of inorganic arsenicals and their methylated metabolites were investigated in male C57BL/6 mice exposed to four arsenic species (arsenite [iAs]III, arsenate [iAs]V, monomethylarsonate [MMA]V, and dimethylarsinate [DMA]V) at four doses (control [C]: 0 µg/g, simulation [S]: 0.91 µg/g, medium [M]: 9.1 µg/g and high [H]: 30 µg/g) according to the arsenical composition in rice for 8 and 16 weeks. No adverse effects were observed, while body weight gain decreased in group H. Increases in total arsenic concentrations (CtAs) and histopathological changes in the tissues occurred in all of the test groups. CtAs presented a tendency of kidney > intestine > liver > blood and were time-/dose-dependent in the liver and kidney in groups M and H. In the intestine and blood, abundant iAs (23%-28% in blood and 36%-49% in intestine) was detected in groups M and H, and CtAs decreased in group H from the 8th week to the 16th week. PMI decreased in the liver and SMI decreased in the kidney. These results indicate that the three tissues are injured through food arsenic. The intestine can also accumulate food arsenic, and the high arsenic dose will cause a deficiency in the absorbing function of the intestine. Thus, long-term exposure to arsenic-contaminated rice should be taken seriously attention.