Does weight loss improve semen quality and reproductive hormones? results from a cohort of severely obese men

<p>Abstract</p> <p>Background</p> <p>A 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.</p> <p>Methods</p> <p>In this pilot cohort study, 43 men with BMI > 33 kg/m²were 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.</p> <p>Results</p> <p>Participants 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)].</p> <p>Conclusion</p> <p>This 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.</p

Reactive oxygen species and male reproductive hormones

Reports of the increasing incidence of male infertility paired with decreasing semen quality have triggered studies on the effects of lifestyle and environmental factors on the male reproductive potential. There are numerous exogenous and endogenous factors that are able to induce excessive production of reactive oxygen species (ROS) beyond that of cellular antioxidant capacity, thus causing oxidative stress. In turn, oxidative stress negatively affects male reproductive functions and may induce infertility either directly or indirectly by affecting the hypothalamus-pituitary-gonadal (HPG) axis and/or disrupting its crosstalk with other hormonal axes. This review discusses the important exogenous and endogenous factors leading to the generation of ROS in different parts of the male reproductive tract. It also highlights the negative impact of oxidative stress on the regulation and cross-talk between the reproductive hormones. It further describes the mechanism of ROS-induced derangement of male reproductive hormonal profiles that could ultimately lead to male infertility. An understanding of the disruptive effects of ROS on male reproductive hormones would encourage further investigations directed towards the prevention of ROS-mediated hormonal imbalances, which in turn could help in the management of male infertility

Body Mass Index Is Associated with Impaired Semen Characteristics and Reduced Levels of Anti-Müllerian Hormone across a Wide Weight Range

There is still controversy as to how body mass index (BMI) affects male reproduction. We investigated how BMI is associated with semen quality and reproductive hormones in 166 men, including 38 severely obese men. Standard semen analysis and sperm DNA integrity analysis were performed, and blood samples were analysed for reproductive hormones. Adjusted for age and time of abstinence, BMI was negatively associated with sperm concentration (B = -0.088, P = 0.009), total sperm count (B = -0.223, P = 0.001), progressive sperm motility (B = -0.675, P = 0.007), normal sperm morphology (B = -0.078, P = 0.001), and percentage of vital spermatozoa (B = -0.006, P = 0.027). A negative relationship was observed between BMI and total testosterone (B = -0.378, P < 0.001), sex hormone binding globulin (B = -0.572, P < 0.001), inhibin B (B = -3.120, P < 0.001) and anti-Müllerian hormone (AMH) (B = -0.009, P < 0.001). Our findings suggest that high BMI is negatively associated with semen characteristics and serum levels of AMH

Quantitative global and gene-specific promoter methylation in relation to biological properties of neuroblastomas

<p>Abstract</p> <p>Background</p> <p>In this study we aimed to quantify tumor suppressor gene (TSG) promoter methylation densities levels in primary neuroblastoma tumors and cell lines. A subset of these TSGs is associated with a CpG island methylator phenotype (CIMP) in other tumor types.</p> <p>Methods</p> <p>The study panel consisted of 38 primary tumors, 7 established cell lines and 4 healthy references. Promoter methylation was determined by bisulphate Pyrosequencing for 14 TSGs; and <it>LINE-1</it> repeat element methylation was used as an indicator of global methylation levels.</p> <p>Results</p> <p>Overall mean TSG Z-scores were significantly increased in cases with adverse outcome, but were unrelated to global <it>LINE-1</it> methylation. CIMP with hypermethylation of three or more gene promoters was observed in 6/38 tumors and 7/7 cell lines. Hypermethylation of one or more TSG (comprising TSGs <it>BLU</it>, <it>CASP8</it>, <it>DCR2</it>, <it>CDH1</it>, <it>RASSF1A</it> and RASSF2) was evident in 30/38 tumors. By contrast only very low levels of promoter methylation were recorded for <it>APC</it>, <it>DAPK1</it>, <it>NORE1A</it>, <it>P14</it>, <it>P16</it>, <it>TP73</it>, <it>PTEN</it> and <it>RARB</it>. Similar involvements of methylation instability were revealed between cell line models and neuroblastoma tumors. Separate analysis of two proposed <it>CASP8</it> regulatory regions revealed frequent and significant involvement of CpG sites between exon 4 and 5, but modest involvement of the exon 1 region.</p> <p>Conclusions/significance</p> <p>The results highlight the involvement of TSG methylation instability in neuroblastoma tumors and cell lines using quantitative methods, support the use of DNA methylation analyses as a prognostic tool for this tumor type, and underscore the relevance of developing demethylating therapies for its treatment.</p

Overweight in young males reduces in a half the normal pregnancy success in rabbit model

[EN] Semen quality has certainly declined over the past few decades, possibly owing to modern lifestyle factors. In this sense, the role of overweight and obesity in the development of subfertility in males has generated a considerable amount of interest in recent years. However, there is no consensus on whether overweight or obesity impaired sperm quality. Thus, based on the ongoing debate about risk factors for subfertility associated with overweight and obesity in men, this study was designed to investigate the effect of overweight on sperm quality parameters and fertility success in randomized controlled trial in a rabbit model. Fourteen male rabbits were randomly assigned to a control group in which nutritional requirements were satisfied or a group fed to satiety from 12 to 32 weeks of age. At 24 weeks of age, semen samples were analysed weekly by conventional semen analysis for 8 weeks. In addition, during the trial female rabbits were artificially inseminated by each male to assess the fertility success and the number of offspring. Young males fed to satiety were associated with a significant increase in body weight (13.6% overweight) and perirenal fat thickness (5%). Male overweight presented a significant decrease in sperm concentration. There were no differences in the remaining sperm parameters. However, male overweight showed a clear and significant decrease in fertility success (control group, 64±8.9% versus fed to satiety group, 35±9.2%), but not in the number of offspring. Taken together, our findings provide new evidence on the loss of fertility induced by overweight in males.This research was supported by the projects: Spanish Research project AGL2014-5 3405-C2-1-P Comision Interministerial de Ciencia y Tecnologia (FMJ, JSV). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Marco-Jiménez, F.; Vicente Antón, JS. (2017). Overweight in young males reduces in a half the normal pregnancy success in rabbit model. PLoS ONE. 12(7):1-11. https://doi.org/10.1371/journal.pone.0180679S11112