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Maternal vitamin D levels during pregnancy may be important for reproductive health in male offspring by regulating cell proliferation and differentiation during development. We conducted a follow-up study of 827 young men from the Fetal Programming of Semen Quality (FEPOS) cohort, nested in the Danish National Birth Cohort to investigate if maternal vitamin D levels were associated with measures of reproductive health in adult sons. These included semen characteristics, testes volume, and reproductive hormone levels and were analysed according to maternal vitamin D (25(OH)D3) levels during pregnancy. In addition, an instrumental variable analysis using seasonality in sun exposure as an instrument for maternal vitamin D levels was conducted. We found that sons of mothers with vitamin D levels  75 nmol/L. Continuous models, spline plots and an instrumental variable analysis supported these findings. Low maternal vitamin D levels were associated with lower testes volume and lower total sperm count with indications of dose-dependency. Maternal vitamin D level above 75 nmol/L during pregnancy may be beneficial for testes function in adult sons.

Background: The organochlorine dichlorodiphenyltrichloroethane (DDT) is banned worldwide owing to its negative health effects. It is exceptionally used as an insecticide for malaria control. Exposure occurs in regions where DDT is applied, as well as in the Arctic, where its endocrine disrupting metabolite, p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) accumulates in marine mammals and fish. DDT and p,p'- DDE exposures are linked to birth defects, infertility, cancer, and neurodevelopmental delays. Of particular concern is the potential of DDT use to impact the health of generations to come via the heritable sperm epigenome. Objectives: The objective of this study was to assess the sperm epigenome in relation to p,p'-DDE serum levels between geographically diverse populations. Methods: In the Limpopo Province of South Africa, we recruited 247 VhaVenda South African men and selected 50 paired blood serum and semen samples, and 47 Greenlandic Inuit blood and semen paired samples were selected from a total of 193 samples from the biobank of the INUENDO cohort, an EU Fifth Framework Programme Research and Development project. Sample selection was based on obtaining a range of p,p'- DDE serum levels (mean = 870.734 [+ or -] 134.030 ng/mL). We assessed the sperm epigenome in relation to serump,p'-DDE levels using MethylC-Capture-sequencing (MCCseq) and chromatin immunoprecipitation followed by sequencing (ChIP-seq). We identified genomic regions with altered DNA methylation (DNAme) and differential enrichment of histone H3 lysine 4 trimethylation (H3K4me3) in sperm. Results: Differences in DNAme and H3K4me3 enrichment were identified at transposable elements and regulatory regions involved in fertility, disease, development, and neurofunction. A subset of regions with sperm DNAme and H3K4me3 that differed between exposure groups was predicted to persist in the preimplantation embryo and to be associated with embryonic gene expression. Discussion: These findings suggest that DDT and p,p'-DDE exposure impacts the sperm epigenome in a dose-response- like manner and may negatively impact the health of future generations through epigenetic mechanisms. Confounding factors, such as other environmental exposures, genetic diversity, and selection bias, cannot be ruled out. https://doi.org/10.1289/EHP12013, Introduction Dichlorodiphenyltrichloroethane (DDT) is a lipophilic organochlorine pollutant that is listed under the Stockholm Convention, with the objective to eliminate its use so as to protect human health and the [...]

The article discusses the DOC*X-Generation cohort, a Danish pregnancy cohort that was established to study the impact of occupational exposures during pregnancy. The cohort includes data on parental job titles, demographics, birth outcomes, and health outcomes for both parents and children. The data shows changes in factors such as the age of the mother and tobacco smoking during pregnancy over time. The document provides information on pregnancy outcomes, including miscarriages, induced abortions, stillborns, and live-borns, and also examines the social gradient in relation to pre-term birth. The study found stable prevalence rates for fetal deaths and a decrease in induced abortions, while the prevalence of congenital malformations and extremely pre-term births increased. The study also confirms the association between tobacco smoking and pre-term birth. The DOC*X-Generation cohort is a valuable resource for research on occupational risk for parental and offspring health, although it only includes women who have been part of the labor market. [Extracted from the article]

Background: Poor male fecundity is of concern and warrants the identification of potential modifiable risk factors. Short and long sleep duration might be risk factors for poor male fecundity although evidence in this research field is inconsistent. Objectives: To investigate the association between sleep duration and biomarkers of male fecundity in young men. Materials and methods: We conducted a cross‐sectional study of 1,055 young men from the Fetal Programming of Semen Quality (FEPOS) cohort, Denmark, 2017–2019. Sleep duration was obtained from an online survey answered by the participants prior to the clinical visit, where semen and blood samples were obtained, and testis volume was self‐assessed using an Orchidometer. Percentage differences in semen characteristics, testes volume, and reproductive hormone levels were analysed according to sleep duration using multivariable negative binomial regression models. Sleep duration was dichotomised (recommended (6–9 h/night) versus deviant sleep) and visualised continuously as restricted cubic spline plots. Results: Deviation from recommended sleep duration was associated with higher high DNA stainability (HDS) of 5% (95% CI: −1%; 13%), higher testosterone of 3% (95% CI: 0%; 7%) and higher free androgen index (FAI) of 6% (95% CI: 0%; 13%). The spline plots overall supported these results, suggesting u‐shaped associations between sleep duration and HDS, testosterone and FAI, a linear association between sleep duration and semen volume and sex hormone binding globulin (SHBG) and an inverse u‐shaped association with normal morphology. Discussion: Information on sleep duration was obtained by self‐report in broad categories with at least 3 h intervals. We were not able to investigate short or long sleep duration separately, since only few participants reported this. Conclusion: Sleep duration was associated with some biomarkers of fecundity in young men. Maintaining a recommended sleep duration may thus be beneficial for young men with regard to reproductive health. [ABSTRACT FROM AUTHOR]

Background: Concerns remain about the human reproductive toxicity of the widespread per- and polyfluoroalkyl substances (PFAS) during early stages of development. Objectives: We examined associations between maternal plasma PFAS levels during early pregnancy and male offspring reproductive function in adulthood. Methods: The study included 864 young men (age range:18.9-21.2 y) from the Fetal Programming of Semen Quality (FEPOS) cohort established between 2017 and 2019. Plasma samples from their mothers, primarily from the first trimester, were retrieved from the Danish National Biobank and levels of 15 PFAS were measured. Seven PFAS had detectable levels above the limit of detection in >80% of the samples and were included in analyses. Semen quality, testicular volume, and levels of reproductive hormones and PFAS were assessed in the young men. We used weighted quantile sum (WQS) regression to estimate the associations between combined exposure to maternal PFAS and reproductive function, and negative binomial regression to estimate the associations of single substances, while adjusting for a range of a priori-defined fetal and postnatal risk factors. Results: By a 1-unit increase in the WQS index, combined maternal PFAS exposure was associated with lower sperm concentration (-8%; 95% CI: -16%, -1%), total sperm count (-10%; 95% CI: -17%, -2%), and a higher proportion of nonprogressive and immotile sperm (5%; 95% CI: 1%, 8%) in the young men. Different PFAS contributed to the associations with varying strengths; however, perfluoroheptanoic acid was identified as the main contributor in the analyses of all three outcomes despite the low concentration. We saw no clear association between exposure to maternal PFAS and testicular volume or reproductive hormones. Discussion: In a sample of young men from the general Danish population, we observed consistent inverse associations between exposure to maternal PFAS and semen quality. The study needs to be replicated in other populations, taking combined exposure, as well as emerging short-chain PFAS, into consideration. https://doi.org/10.1289/EHP10285, Introduction Per- and polyfluoroalkyl substances (PFAS) have been in use since the 1940s and now constitute a group of more than 5,000 manmade chemicals. (1,2) Their water-, dirt-, and oil-repellent [...]