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Background/Objectives: The aim of this study was to investigate the association between antioxidant intake and antral follicle count (AFC), a marker of ovarian reserve, in women attending a fertility clinic. Methods: We conducted an observational study with 567 women undergoing infertility evaluation at the Massachusetts General Hospital Fertility Center, who were enrolled in the Environment and Reproductive Health (EARTH) study. Participants filled out the lifestyle and health questionnaires and a validated food frequency questionnaire (FFQ) for assessing habitual dietary intake and underwent a transvaginal ultrasound to measure AFC. Intake of nutrients with direct antioxidant capacity (vitamin A, C, and E and carotenoids) and intake of antioxidant food sources were estimated from the FFQ. Adjusted Poisson regression models were fitted to assess the relationships between antioxidants and AFC while adjusting for potential confounders. Non-linearity was assessed with restricted cubic splines. Results: The median (interquartile range) age and AFC of participants were 35.0 (32.0–38.0) years and 13 (9–18), respectively. Our findings revealed a non-linear association between lycopene intake and AFC. There was a positive linear association with the highest AFC among women consuming approximately 6000 mcg/day of lycopene (p for non-linearity = 0.003). An inverse association was observed between retinol intake, predominantly from dairy foods, and AFC among women aged under 35 years (p-trend < 0.001 and 0.01, respectively). Conclusions: Our findings suggest that lycopene intake might influence the ovarian reserve in fertility patients. The observed inverse association with retinol, if confirmed, may reflect biological mechanisms different from oxidative stress. The underlying mechanisms of these associations remain to be elucidated and warrant further investigation. [ABSTRACT FROM AUTHOR]

Background: Epidemiologic studies of the effects of parental preconception paraben exposures on child behavior are limited despite emerging evidence suggesting that such exposures may affect offspring neurodevelopment. Objective: We investigated whether maternal and paternal preconception and maternal pregnancy urinary concentrations of parabens were associated with child behavior. Methods: We analyzed data from the Preconception Environmental exposure And Childhood health Effects Study, an ongoing prospective cohort of children aged 6–13 years and their parents. We estimated covariate‐adjusted associations of loge‐transformed urinary methyl, propyl, and butyl paraben concentrations (individually using linear regression models and as a mixture using quantile g‐computation) collected prior to conception and during pregnancy with Behavioral Assessment System for Children‐3 and Behavior Rating Inventory of Executive Function T‐scores (higher scores indicate more problem behaviors). Results: This analysis included 140 mothers, 81 fathers, and 171 children (25 sets of twins); parents were predominantly non‐Hispanic white (88% for both mothers and fathers). In single paraben models, higher paternal preconception urinary propyl and methyl paraben concentrations were associated with higher Internalizing Problem T‐scores (propyl paraben β$\beta \;$= 1.7; 95% confidence interval: 0.6, 2.8, methyl paraben β$\beta \;$= 2.2; 95% confidence interval: 0.5, 3.9) and higher Behavioral Symptom Index T‐scores (propyl paraben β$\beta \;$= 1.4; 95% confidence interval: 0.3, 2.5, methyl paraben β$\beta \;$= 1.6; 95% confidence interval: ‐0.1, 3.3). Each quantile increase in the paternal mixture of three parabens was associated with a 3.4 (95% confidence interval: 0.67, 6.1) and 2.5 (95% confidence interval: 0.01, 5.0) increased internalizing problem and Behavioral Symptom Index T‐scores respectively. Higher paternal preconception (β$\beta \;$= 1.0; 95% confidence interval: 0.04, 1.9) and maternal preconception (β$\beta \;$= 1.1 95% confidence interval: ‐0.1, 2.2) concentrations of propyl paraben were associated with higher Behavior Rating Inventory of Executive Function Metacognition Index T‐scores in children, but the paraben mixtures was not. Conclusion: In this cohort, paternal preconception urinary concentrations of propyl and methyl paraben were associated with worse parent‐reported child behaviors. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Are markers of epigenetic age acceleration in follicular fluid associated with outcomes of ovarian stimulation? SUMMARY ANSWER Increased epigenetic age acceleration of follicular fluid using the Horvath clock, but not other epigenetic clocks (GrimAge and Granulosa Cell), was associated with lower peak estradiol levels and decreased number of total and mature oocytes. WHAT IS KNOWN ALREADY In granulosa cells, there are inconsistent findings between epigenetic age acceleration and ovarian response outcomes. STUDY DESIGN, SIZE, DURATION Our study included 61 women undergoing IVF at an academic fertility clinic in the New England area who were part of the Environment and Reproductive Health Study (2006–2016). PARTICIPANTS/MATERIALS, SETTING, METHODS Participants provided a follicular fluid sample during oocyte retrieval. DNA methylation of follicular fluid was assessed using a genome-wide methylation screening tool. Three established epigenetic clocks (Horvath, GrimAge, and Granulosa Cell) were used to predict DNA-methylation-based epigenetic age. To calculate the age acceleration, we regressed epigenetic age on chronological age and extracted the residuals. The association between epigenetic age acceleration and ovarian response outcomes (peak estradiol levels, follicle stimulation hormone, number of total, and mature oocytes) was assessed using linear and Poisson regression adjusted for chronological age, three surrogate variables (to account for cellular heterogeneity), race, smoking status, initial infertility diagnosis, and stimulation protocol. MAIN RESULTS AND ROLE OF CHANCE Compared to the median chronological age of our participants (34 years), the Horvath clock predicted, on an average, a younger epigenetic age (median: 24.2 years) while the GrimAge (median: 38.6 years) and Granulosa Cell (median: 39.0 years) clocks predicted, on an average, an older epigenetic age. Age acceleration based on the Horvath clock was associated with lower peak estradiol levels (−819.4 unit decrease in peak estradiol levels per standard deviation increase; 95% CI: −1265.7, −373.1) and fewer total (% change in total oocytes retrieved per standard deviation increase: −21.8%; 95% CI: −37.1%, −2.8%) and mature oocytes retrieved (% change in mature oocytes retrieved per standard deviation increase: −23.8%; 95% CI: −39.9%, −3.4%). The age acceleration based on the two other epigenetic clocks was not associated with markers of ovarian response. LIMITATIONS, REASONS FOR CAUTION Our sample size was small and we did not specifically isolate granulosa cells from follicular fluid samples so our samples could have included mixed cell types. WIDER IMPLICATIONS OF THE FINDINGS Our results highlight that certain epigenetic clocks may be predictive of ovarian stimulation outcomes when applied to follicular fluid; however, the inconsistent findings for specific clocks across studies indicate a need for further research to better understand the clinical utility of epigenetic clocks to improve IVF treatment. STUDY FUNDING/COMPETING INTEREST(S) The study was supported by grants ES009718, ES022955, ES000002, and ES026648 from the National Institute of Environmental Health Sciences (NIEHS) and a pilot grant from the NIEHS-funded HERCULES Center at Emory University (P30 ES019776). RBH was supported by the Emory University NIH Training Grant (T32-ES012870). TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

We examined whether mixtures of urinary concentrations of bisphenol A (BPA), parabens and phthalate metabolites were associated with serum lipid levels among 175 pregnant women who enrolled in the Environment and Reproductive Health (EARTH) Study (2005–2017), including triglycerides, total cholesterol, high-density lipoprotein (HDL), non-HDL, and low-density lipoprotein (LDL). We applied Bayesian Kernel Machine Regression (BKMR) and quantile g-computation while adjusting for confounders. In the BKMR models, we found no associations between chemical mixture and lipid levels, e.g., total cholesterol [mean difference (95% CRI, credible interval) = 0.02 (−0.31, 0.34)] and LDL [mean difference (95% CRI) = 0.10 (−0.22, 0.43)], when comparing concentrations at the 75th to the 25th percentile. When stratified by BMI, we found suggestive positive relationships between urinary propylparaben and total cholesterol and LDL among women with high BMI [mean difference (95% CRI) = 0.25 (−0.26, 0.75) and 0.35 (−0.25, 0.95)], but not with low BMI [mean difference (95% CRI) = 0.00 (−0.06, 0.07) and 0.00 (−0.07, 0.07)]. No association was found by quantile g-computation. This exploratory study suggests mixtures of phenol and phthalate metabolites were not associated with serum lipid levels during pregnancy, while there were some suggestive associations for certain BMI subgroups. Larger longitudinal studies with multiple assessments of both exposure and outcome are needed to corroborate these novel findings. [ABSTRACT FROM AUTHOR]