BackgroundA high body mass index (BMI) has been associated with reduced semen quality and male subfecundity, but no studies following obese men losing weight have yet been published. We examined semen quality and reproductive hormones among morbidly obese men and studied if weight loss improved the reproductive indicators.MethodsIn this pilot cohort study, 43 men with BMI > 33 kg/m2 were followed through a 14 week residential weight loss program. The participants provided semen samples and had blood samples drawn, filled in questionnaires, and had clinical examinations before and after the intervention. Conventional semen characteristics as well as sperm DNA integrity, analysed by the sperm chromatin structure assay (SCSA) were obtained. Serum levels of testosterone, estradiol, sex hormone-binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH) and inhibin B (Inh-B) were measured.ResultsParticipants were from 20 to 59 years of age (median = 32) with BMI ranging from 33 to 61 kg/m2. At baseline, after adjustment for potential confounders, BMI was inversely associated with sperm concentration (p = 0.02), total sperm count (p = 0.02), sperm morphology (p = 0.04), and motile sperm (p = 0.005) as well as testosterone (p = 0.04) and Inh-B (p = 0.04) and positively associated to estradiol (p < 0.005). The median (range) percentage weight loss after the intervention was 15% (3.5 - 25.4). Weight loss was associated with an increase in total sperm count (p = 0.02), semen volume (p = 0.04), testosterone (p = 0.02), SHBG (p = 0.03) and AMH (p = 0.02). The group with the largest weight loss had a statistically significant increase in total sperm count [193 millions (95% CI: 45; 341)] and normal sperm morphology [4% (95% CI: 1; 7)].ConclusionThis study found obesity to be associated with poor semen quality and altered reproductive hormonal profile. Weight loss may potentially lead to improvement in semen quality. Whether the improvement is a result of the reduction in body weight per se or improved lifestyles remains unknown.

Background: Perfluorinated alkyl acids (PFAAs), persistent chemicals with unique water-, dirt-, and oil-repellent properties, are suspected of having endocrine-disrupting activity. The PFAA compounds perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) are found globally in humans; because they readily cross the placental barrier, in utero exposure may be a cause for concern.Objectives: We investigated whether in utero exposure to PFOA and PFOS affects semen quality, testicular volume, and reproductive hormone levels.Methods: We recruited 169 male offspring (19–21 years of age) from a pregnancy cohort established in Aarhus, Denmark, in 1988–1989, corresponding to 37.6% of the eligible sons. Each man provided a semen sample and a blood sample. Semen samples were analyzed for sperm concentration, total sperm count, motility, and morphology, and blood samples were used to measure reproductive hormones. As a proxy for in utero exposure, PFOA and PFOS were measured in maternal blood samples from pregnancy week 30.Results: Multivariable linear regression analysis suggested that in utero exposure to PFOA was associated with lower adjusted sperm concentration (ptrend = 0.01) and total sperm count (ptrend = 0.001) and with higher adjusted levels of luteinizing hormone (ptrend = 0.03) and follicle-stimulating hormone (ptrend = 0.01). PFOS did not appear to be associated with any of the outcomes assessed, before or after adjustment.Conclusions: The results suggest that in utero exposure to PFOA may affect adult human male semen quality and reproductive hormone levels.

E.H.E. was supported by Health Faculty, Aarhus University and Kong Christian Den Tiendes Fond. K.H. and S.F. were supported by an MRC (UK) project grant MR/M012638/1. K.L.H. was supported by grants from Fonden til Lægevidenskabens Fremme, Kong Christian Den Tiendes Fond. K.L.H. and L.S. were supported by the IDEAS grant from Aarhus University Research Foundation (AUFF). There are no conflicts of interest.

E.H.E. was supported by the Health Faculty, Aarhus University and Kong Christian Den Tiendes Fond. K.L.H. was supported by a grant from Fondens til Lægevidenskabens Fremme and Kong Christian Den Tiendes Fond. No authors have competing interests to declare.

The precise timing and sequence of changes in expression of key genes and proteins during human sex-differentiation and onset of steroidogenesis was evaluated by whole-genome expression in 67 first trimester human embryonic and fetal ovaries and testis and confirmed by qPCR and immunohistochemistry (IHC). SRY/SOX9 expression initiated in testis around day 40 pc, followed by initiation of AMH and steroidogenic genes required for androgen production at day 53 pc. In ovaries, gene expression of RSPO1, LIN28, FOXL2, WNT2B, and ETV5, were significantly higher than in testis, whereas GLI1 was significantly higher in testis than ovaries. Gene expression was confirmed by IHC for GAGE, SOX9, AMH, CYP17A1, LIN28, WNT2B, ETV5 and GLI1. Gene expression was not associated with the maternal smoking habits. Collectively, a precise temporal determination of changes in expression of key genes involved in human sex-differentiation is defined, with identification of new genes of potential importance.

Persistent organochlorine pollutants (POPs) are ubiquitous, bioaccumulative compounds with potential endocrine-disrupting effects. They cross the placental barrier thereby resulting in in utero exposure of the developing fetus. The objective of this study was to investigate whether maternal serum concentrations of polychlorinated biphenyls (PCBs) and p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE) during pregnancy are associated with son's semen quality and reproductive hormone levels. During 2008–2009, we recruited 176 male offspring from a Danish cohort of pregnant women who participated in a study in 1988–1989. Each provided semen and blood samples that were analyzed for sperm concentration, total sperm count, motility, and morphology, and reproductive hormone levels, respectively. The maternal blood samples were collected in pregnancy week 30 and were analyzed for the concentrations of six PCBs (PCB-118, -138, -153, -156, -170, and -180) and p,p′-DDE. The potential associations between in utero exposure to ΣPCBs (pmol/ml), Σdioxin like-(DL) PCBs (PCB-118 and -156) (pmol/ml), and p,p′-DDE and semen quality and reproductive hormone levels were investigated using multiple regression. Maternal median (range) exposure levels of ΣPCB, ΣDL-PCB, and p,p′-DDE were 10.0 (2.1–35.0) pmol/ml, 0.8 (0.2–2.7) pmol/ml, and 8.0 (0.7–55.3) pmol/ml, respectively, reflecting typical background exposure levels in the late 1980s in Denmark. Results suggested that in utero exposure to ΣPCB, ΣDL-PCB, and p,p′-DDE was not statistically significantly associated with semen quality measures or reproductive hormone levels. Thus, results based on maternal PCB and p,p′-DDE concentrations alone are not indicative of long-term consequences for male reproductive health; however, we cannot exclude that these POPs in concert with other endocrine-modulating compounds may have adverse effects.

Emerging evidence indicated that many long non-coding (lnc)RNAs function in multiple biological processes and dysregulation of their expression can cause diseases. Most regulatory lncRNAs interact with biological macromolecules such as DNA, RNA, and protein. LncRNAs regulate gene expression through epigenetic modification, transcription, and posttranscription, through DNA methylation, histone modification, and chromatin remodeling. Interestingly, differential lncRNA expression profiles in human oocytes and cumulus cells was recently assessed, however, lncRNAs in human follicle development has not previously been described. In this study, transcriptome dynamics in human primordial, primary and small antral follicles were interrogated and revealed information of lncRNA genes. It is known that some lncRNAs form a complex with paraspeckle proteins and therefore, we extended our transcriptional analysis to include genes encoding paraspeckle proteins. Primordial, primary follicles and small antral follicles was isolated using laser capture micro-dissection from ovarian tissue donated by three women having ovarian tissue cryopreserved before chemotherapy. After RN sequencing, a bioinformatic class comparison was performed and primordial, primary and small antral follicles were found to express several lncRNA and genes encoding paraspeckle proteins. Of particular interest, we detected the lncRNAs XIST, NEAT1, NEAT2 (MALAT1), and GAS5. Moreover, we noted a high expression of FUS, TAF15, and EWS components of the paraspeckles, proteins that belong to the FET (previously TET) family of RNA-binding proteins and are implicated in central cellular processes such as regulation of gene expression, maintenance of genomic integrity, and mRNA/microRNA processing. We also interrogated the intra-ovarian localization of the FUS, TAF15, and EWS proteins using immunofluorescence. The presence and the dynamics of genes that encode lncRNA and paraspeckle proteins may suggest that these may mediate functions in the cyclic recruitment and differentiation of human follicles and could participate in biological processes known to be associated with lncRNAs and paraspeckle proteins, such as gene expression control, scaffold formation and epigenetic control through human follicle development. This comprehensive transcriptome analysis of lncRNAs and genes encoding paraspeckle proteins expressed in human follicles could potentially provide biomarkers of oocyte quality for the development of non-invasive tests to identify embryos with high developmental potential.

The TB test can be suggested for clinical use as a complementary test for standard semen analysis to diagnose male infertility.