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STUDY QUESTION Is there a possible association between prenatal phthalate exposure and late effects in teenage daughters with respect to reproductive hormone levels, uterine volume, and number of ovarian follicles? SUMMARY ANSWER Our study showed subtle associations between phthalate metabolite concentrations in maternal serum from pregnancy or cord blood and LH and insulin-like growth factor 1 (IGF-1) levels as well as uterine volume in their daughters 16 years later. WHAT IS KNOWN ALREADY Endocrine-disrupting environmental chemicals may adversely affect human reproductive health, and many societies have experienced a trend toward earlier puberty and an increasing prevalence of infertility in young couples. The scientific evidence of adverse effects of foetal exposure to a large range of chemicals, including phthalates, on male reproductive health is growing, but very few studies have explored effects on female reproduction. STUDY DESIGN, SIZE, DURATION This follow-up study included 317 teenage daughters who were part of the Copenhagen Mother–Child Cohort, a population-based longitudinal birth cohort of 1210 females born between 1997 and 2002. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 317 female participants (median age 16 years) were examined for weight, height, and menstrual pattern. A serum sample was analysed for concentrations of reproductive hormones, and trans-abdominal 3D ultrasonography was performed to obtain the number of ovarian follicles, ovarian and uterine size. Prenatal maternal serum samples were available for 115 females, and cord blood samples were available for 118 females. These were analysed for concentrations of 32 phthalate metabolites. Weighted quantile sum regression was used for modelling associations of combined prenatal phthalate exposure with the reproductive outcomes in post-menarcheal females. MAIN RESULTS AND THE ROLE OF CHANCE In bivariate correlation analyses, negative significant associations were found between several prenatal phthalate metabolite concentrations and serum hormone concentrations (testosterone, 17-OH-progesterone, and IGF-1) as well as number of ovarian follicles in puberty. Positive significant correlations were found between prenatal phthalate exposure and FSH and sex hormone-binding globulin concentrations. Combined analyses of phthalate exposure (weighted quantile sums) showed significant negative associations with IGF-1 concentration and uterine volume as well as a significant positive association with LH concentration. LIMITATIONS, REASONS FOR CAUTION Phthalate metabolites were measured in serum from single prenatal maternal blood samples and cord blood samples. Potential concomitant exposure to other endocrine-disrupting environmental chemicals before or after birth was not controlled for. The study population size was limited. WIDER IMPLICATIONS OF THE FINDINGS Our results support the need for further research into possible adverse effects of environmental chemicals during foetal development of the female reproductive system. STUDY FUNDING/COMPETING INTEREST(S) The work was supported by The Center on Endocrine Disruptors (CeHoS) under The Danish Environmental Protection Agency and The Ministry of Environment and Food (grant number: MST-621-00 065). No conflicts of interest are declared. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Study Question: Is testicular function associated within father-son pairs?Summary Answer: Familial resemblance in testis volume and serum markers of spermatogenesis was observed in father-son pairs.What Is Known Already: Studies suggest familial clustering of male subfertility and impaired spermatogenesis, but in men from the general population little is known about concordance in testicular function between fathers and sons.Study Design, Size, Duration: This cross-sectional study with simultaneous collection of data in fathers and sons included 72 pairs (144 fathers and sons), unselected regarding testicular function were included.Participants/materials, Setting, Methods: A subgroup of men from the background population and participating in a study on testicular function were asked permission to invite their fathers to participate in a similar setup. Fathers (median age of 53 years) and sons (median age of 19 years) participated in the same study setup including assessment of testis size, having a blood sample taken and analysed for serum levels of reproductive hormones (FSH, inhibin B, LH, testosterone, oestradiol, sex hormone-binding globulin (SHBG) and calculated free testosterone) and delivering a semen sample for assessment of traditional semen parameters. Mixed-effects models were fitted to estimate the familial resemblance as the proportion of variance in markers of testicular function due to shared factors for fathers and sons accounted for using random-effects. Variance components were calculated from both unadjusted and adjusted models.Main Results and the Role Of Chance: After adjustments, variance component analyses showed that familial resemblance between fathers and sons accounted for 48% (P < 0.001) of the variation in testicular volume, 32% (P = 0.009) of the variation in FSH, 31% (P = 0.009) of the variation in the inhibin B/FSH ratio, 33% (P = 0.007) and 45% (P < 0.001) of the variation in testosterone and free testosterone, respectively, and 31% (P = 0.009) of the variation in SHBG. None of the semen parameters were associated within father-son pairs.Limitations, Reasons For Caution: The present study may have lacked power to detect associations for semen quality, as large intra- and inter-individual variation occur in semen parameters.Wider Implications Of the Findings: In this study, testis volume, serum testosterone and serum markers of spermatogenesis including FSH were associated in fathers and sons, suggesting an impact of paternal genetics for testicular function in the son. However, the estimated familial resemblance for spermatogenesis markers highlights that other factors, such as maternal genetics and prenatal as well as adult exposures, are also of major importance for testicular function.Study Funding/competing Interest(s): The study has received funding from Danish Health Authority, Research Fund of the Capital Region of Denmark and Independent Research Fund Denmark (8020-00218B). None of the funders had any role in the study design, collection, analysis or interpretation of data, writing of the paper of publication decisions. The authors have nothing to disclose.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Study Question: Are low vitamin D levels linked with semen quality and sex steroids in infertile men?Summary Answer: Infertile men with vitamin D deficiency had lower sperm motility, total numbers of motile sperm, Inhibin B, sex-hormone-binding-globulin (SHBG) and testosterone/estradiol ratio, but higher levels of free sex steroids, than infertile men with normal vitamin D levels.What Is Known Already: Low vitamin D levels have been associated with decreased sperm motility in healthy men, but a relationship between vitamin D and calcium with semen quality and especially sex steroids has not been sufficiently described in infertile men.Study Design, Size, Duration: This study comprises baseline characteristics of 1427 infertile men screened from 2011 to 2014 for inclusion in a randomized clinical trial, the Copenhagen-Bone-Gonadal Study.Participants/materials, Setting, Methods: In total 1427 infertile men, consecutively referred to our tertiary andrological centre for fertility workup, underwent a physical examination and had semen quality assessed based on two samples and blood analysed for serum testosterone, SHBG, estradiol, inhibin B, luteinizing hormone, follicle-stimulating hormone (FSH), 25-hydroxyvitamin D (25-OHD), ionized calcium (Ca(2+)) and karyotype. There were 179 men excluded due to serious comorbidities or anabolic steroid usage, leaving 1248 patients for analyses.Main Results and the Role Of Chance: Men with 25-OHD >75 nmol/l had higher sperm motility and 66 and 111% higher total numbers of motile spermatozoa after 45 and 262 min, respectively, than men with 25-OHD <25 nmol/l (all P < 0.05). SHBG levels and testosterone/estradiol ratios were 15 and 14% lower, respectively, while free testosterone and estradiol ratios were 6 and 13% higher, respectively, in men with 25-OHD <25 nmol/l (all P < 0.05). Men with lower Ca(2+) levels had higher progressive sperm motility and inhibin B/FSH ratio but lower testosterone/estradiol ratio (all P < 0.05).Limitations, Reasons For Caution: All outcomes presented are predefined end-points but inferral of causality is compromised by the descriptive study design. It remains to be shown whether the links between vitamin D, calcium, semen quality and sex steroids in infertile men are causal.Wider Implications Of the Findings: The associations between vitamin D deficiency and low calcium with semen quality and sex steroids support the existence of a cross-link between regulators of calcium homeostasis and gonadal function in infertile men.Study Funding/competing Interests: This study was supported by the Danish Agency for Science, Technology and Innovation, Hørslev Fonden, Danish Cancer Society and Novo Nordisk Foundation. There are no conflicts of interest.Trial Registration Number: NCT01304927.Date Of Trial Registration: 25 February 2011.Date Of Enrolment Of First Patient: 8 March 2011. [ABSTRACT FROM AUTHOR]