Fetal programming of semen quality (Fepos) cohort – a dnbc male-offspring cohort

Background: Prenatal exposures may contribute to male infertility in adult life, but large-scale epidemiological evidence is still lacking. The Fetal Programming of Semen quality (FEPOS) cohort was founded to provide means to examine if fetal exposures can interfere with fetal reproductive development and ultimately lead to reduced semen quality and reproductive hormone imbalances in young adult men. Methods: Young adult men at least 18 years and 9 months of age born to women in the Danish National Birth Cohort living in relative proximity to Copenhagen or Aarhus and for whom a maternal blood sample and two maternal interviews during pregnancy were available were invited to FEPOS. Recruitment began in March 2017 and ended in December 2019. The participants answered a comprehensive questionnaire and underwent a physical examination where they delivered a semen, urine, and hair sample, measured their own testicular volume, and had blood drawn. Results: In total 21,623 sons fulfilled eligibility criteria of whom 5697 were invited and 1058 participated making the response rate 19%. Semen characteristics did not differ between sons from the Copenhagen and Aarhus clinics. When comparing the FEPOS semen parameters to similar cohorts, the median across all semen characteristics was slightly lower for FEPOS participants, although with smaller variation. Conclusion: With its 1058 young adult men, the FEPOS cohort is the largest population-based male-offspring cohort worldwide specifically designed to investigate prenatal determinants of semen quality. Wide-ranging information on maternal health, lifestyle, socioeconomic status, occupation, and serum concentrations of potential reproductive toxicants during pregnancy combined with biological markers of fertility in their sons collected after puberty allow for in-depth investigations of the ‘fetal origins of adult disease hypothesis’

Вітання Президента України В.Ф. Януковича з нагоди 50-річчя обрання академіка Б.Є. Патона президентом Національної академії наук України

Phthalates which are widely used, are ubiquitous in the environment and in some human tissues. It is generally accepted that phthalates exert their toxic action by inhibiting Leydig cell synthesis of testosterone, but in vitro studies have also shown anti-androgenic effects at the receptor level. Some cross-sectional studies have shown inverse associations between urinary levels of phthalates and reproductive hormones, but results are conflicting and the evidence base is limited. The aim of this study was to investigate if levels of di-2-ethylhexyl phthalate (DEHP) and diisononyl phthalate (DiNP) metabolites in serum are associated with serum concentrations of male reproductive hormones and semen quality. A secondary aim was to investigate metabolic pathways of DEHP and DiNP on semen quality and reproductive hormones. A cross-sectional sample of 589 spouses of pregnant women from Greenland, Poland and Ukraine were enrolled between 2002 and 2004. The men gave semen and blood samples and were interviewed. Six phthalate metabolites of DEHP and DiNP were measured by liquid chromatography tandem mass spectrometry in serum. The metabolites were summed according to their molar weight. We observed significant inverse associations between serum levels of the metabolites, the proxies and serum testosterone. Negative associations were also discovered between some metabolites and sex hormone-binding globulin, semen volume and total sperm count Findings are compatible with a weak anti-androgenic action of DEHP metabolites, but less so for DiNP metabolites. Metabolic pathways differed significantly between the three study sites, but without major effect on semen quality or reproductive hormones. (C) 2014 Elsevier Ltd. All rights reserved

The epidemiologic evidence linking prenatal and postnatal exposure to endocrine disrupting chemicals with male reproductive disorders:a systematic review and meta-analysis

BACKGROUND: More than 20 years ago, it was hypothesized that exposure to prenatal and early postnatal environmental xenobiotics with the potential to disrupt endogenous hormone signaling might be on the causal path to cryptorchidism, hypospadias, low sperm count and testicular cancer. Several consensus statements and narrative reviews in recent years have divided the scientific community and have elicited a call for systematic transparent reviews. We aimed to fill this gap in knowledge in the field of male reproductive disorders. OBJECTIVE AND RATIONALE: The aim of this study was to systematically synthesize published data on the risk of cryptorchidism, hypospadias, low sperm counts and testicular cancer following in utero or infant exposure to chemicals that have been included on the European Commission's list of Category 1 endocrine disrupting chemicals defined as having documented adverse effects due to endocrine disruption in at least one intact organism. SEARCH METHODS: A systematic literature search for original peer reviewed papers was performed in the databases PubMed and Embase to identify epidemiological studies reporting associations between the outcomes of interest and exposures documented by biochemical analyses of biospecimens including maternal blood or urine, placenta or fat tissue as well as amnion fluid, cord blood or breast milk; this was followed by meta-analysis of quantitative data. OUTCOMES: The literature search resulted in 1314 references among which we identified 33 papers(28 study populations) fulfilling the eligibility criteria. These provided 85 risk estimates of links between persistent organic pollutants and rapidly metabolized compounds (phthalates and Bisphenol A) and male reproductive disorders. The overall odds ratio (OR) across all exposures and outcomes was 1.11 (95% CI 0.91–1.35). When assessing four specific chemical subgroups with sufficient data for meta-analysis for all outcomes, we found that exposure to one of the four compounds, p,p′-DDE, was related to an elevated risk: OR 1.35 (95% CI 1.04–1.74). The data did not indicate that this increased risk was driven by any specific disorder. WIDER IMPLICATIONS: The current epidemiological evidence is compatible with a small increased risk of male reproductive disorders following prenatal and postnatal exposure to some persistent environmental chemicals classified as endocrine disruptors but the evidence is limited. Future epidemiological studies may change the weight of the evidence in either direction. No evidence of distortion due to publication bias was found, but exposure–response relationships are not evident. There are insufficient data on rapidly metabolized endocrine disruptors and on specific exposure–outcome relations. A particular data gap is evident with respect to delayed effects on semen quality and testicular cancer. Although high quality epidemiological studies are still sparse, future systematic and transparent reviews may provide pieces of evidence contributing to the narrative and weight of the evidence assessments in the field

Physical Activity and Subsequent Change in Body Weight, Composition and Shape:Effect Modification by Familial Overweight

BACKGROUND: Physical activity (PA) has been shown to attenuate the genetic risk of obesity as measured using polygenic risk scores. However, familial obesity history might be an easier predictor. We examined associations between PA and subsequent changes in BMI, body fat percentage (BF%) and waist circumference (WC) among participants with and without adiposity and a familial overweight. METHODS: In total, 1971 participants from the Danish MONICA cohort were included. Mean differences for 6-year changes in BMI, BF% and WC across PA levels were estimated. Association between walking and biking and subsequent change in adiposity were analysed. Effect modification by familial obesity was assessed by adding product terms to the models. RESULTS: We observed weak associations between leisure PA level and changes in WC [participants with low PA: 3.4 cm (95%CI: 2.8;4.0), participants with high PA: 2.4 cm (95%CI: 1.8;3.0)], with no evidence of effect modification by familial obesity. We found effect modification in analyses on walking and biking in relation to changes in BMI (P-interaction<0.01) and BF% (P-interaction=0.04), suggesting lower gain with more hours of activity among participants with adiposity and familial overweight. CONCLUSIONS: The results were modest but suggested that PA, especially walking and biking, may prevent future adiposity

Duration of exclusive breastfeeding may be related to eating behaviour and dietary intake in obesity prone normal weight young children.

Infants who are breastfed are introduced to a variety of flavours from the maternal milk, and thus the transition from maternal milk to complementary foods may be easier for these children. The aim of this study was to investigate if duration of exclusive breastfeeding was associated with pickiness or dietary intake of vegetables, fruit, starchy foods or sugar sweetened beverages among obesity prone normal weight children aged 2-6 years. This cohort study was based on data from the Healthy Start primary intervention study, the Danish Medical Birth registry and the Danish Health Visitor's Child Health Database. Infant feeding was registered by health nurses while home-visiting the mother and child up to four times within the first year. Information on eating behaviour and diet intake at age 2-6 years was obtained by parents. Crude and adjusted logistic and general linear regression models were used to investigate associations. A total of 236 children had complete information on all variables. Data showed lower odds of picky eating behaviour when exclusively breastfed until age 4-5 months compared to exclusively breastfed for 0-1 months (OR = 0.35, 95CI = 0.16;0.76, p = 0.008). In the crude analysis only, exclusively breastfed until age 6-10 months was associated with a higher daily intake of vegetables (p = 0.04). This study suggests that exclusive breastfeeding duration seems to influence pickiness and may contribute to facilitate the consumption of more vegetables in later childhood in obesity prone normal weight children

Dietary trans-fatty acid intake in relation to cancer risk : a systematic review and meta-analysis

Context Apart from ruminant fat, trans-fatty acids are produced during the partial hydrogenation of vegetable oils, (eg, in the production of ultraprocessed foods). Harmful cardiovascular effects of trans-fatty acids are already proven, but the link with cancer risk has not yet been summarized. Objective A systematic review (following PRISMA guidelines) – including observational studies on the association of trans-fatty acid intake with any cancer risk – was conducted, with no limitations on population types. Data Sources The electronic databases PubMed and Embase were searched to identify relevant studies. Data Extraction This systematic review included 46 articles. Quality was assessed via the Newcastle-Ottawa scale. Meta-analyses were conducted if at least 4 articles exploring the same transfat-cancer pairings were found. Data analysis Nineteen cancer types have been researched in cohort and case-control studies on trans-fatty acids, with breast cancer (n = 17), prostate cancer (n = 11), and colorectal cancer (n = 9) as the most researched. The meta-analyses on total trans-fat showed a significant positive association for prostate cancer (odds ratio [OR] 1.49; 95%CI, 1.13–1.95) and colorectal cancer (OR 1.26; 95%CI, 1.08–1.46) but not for breast cancer (OR 1.12; 95%CI, 0.99–1.26), ovarian cancer (OR 1.10; 95%CI, 0.94–1.28), or non-Hodgkin lymphoma (OR 1.32; 95%CI, 0.99–1.76). Results were dependent on the fatty acid subtype, with even cancer-protective associations for some partially hydrogenated vegetable oils. Enhancing moderators in the positive transfat-cancer relation were gender (direction was cancer-site specific), European ancestry, menopause, older age, and overweight. Conclusion Despite heterogeneity, higher risk of prostate and colorectal cancer by high consumption of trans-fatty acids was found. Future studies need methodological improvements (eg, using long-term follow-up cancer data and intake biomarkers). Owing to the lack of studies testing trans-fatty acid subtypes in standardized ways, it is not clear which subtypes (eg, ruminant sources) are more carcinogenic

Comparison of Motor Difficulties Measured in the First Year of School among Children Who Attended Rural Outdoor or Urban Conventional Kindergartens

Background: Kindergartens can potentially contribute substantially to the daily level of physical activity and development of motor skills and might be an ideal setting for improving these as a public health initiative. We aimed to examine whether children from rural outdoor kindergartens had a lower risk of motor difficulties than children from urban conventional kindergartens. Methods: Motor test results were measured during the first school year by school health nurses using a six-item test of gross- and fine motor skills (jumping, handle a writing tool, cutting with a scissor following a line, one-leg stand on each leg, throwing and grabbing). Register-based information was available on potential confounding factors. Results: We included 901 children from outdoor kindergartens and 993 from conventional kindergartens with a mean (SD) age of 6.5 years (0.4). The children from the two types of kindergarten differed according to demographic information, with outdoor kindergarten children more often being from more affluent families (long maternal education level: 47.5% vs. 31.0%, p &lt; 0.0001) and fewer girls attending the outdoor kindergartens (42.7% vs. 49.5%, p = 0.003). In the adjusted models, we found no evidence of differences in the risk of motor difficulties between children attending either type of kindergarten (OR: 0.95, 95%CI: 0.71; 1.27, p = 0.72). Conclusion: Our results do not support outdoor kindergartens as a potential intervention to improve motor abilities among children. Randomized controlled trials are needed to confirm these findings