DNA Methylation as a Mediator of the Association Between Cognitive Ability and Neighborhood Air Pollution in the Fragile Families and Child Wellbeing Study

Exposure to environmental pollutants, especially air pollutants, has been associated with adverse development to humans early in life. Current research suggests that the genetic mechanisms controlling neurological function may be negatively impacted upon exposure to air pollution. However, these studies have been limited by sample size, number of pollutants studied, and timing of the exposure examined. To address these concerns, this study analyzed the cumulative effects of 178 pollutants on participants from a large longitudinal cohort study. The purpose of this study is to assess the mediating role of an epigenetic modification, specifically toxin-induced DNA methylation changes, in the association between cognitive ability and children’s exposure to airborne toxins in large cities in the United States. We find that children who grow up in neighborhoods with higher levels of neurologically hazardous air pollution score lower on measures of academic and intellectual ability at age 9 and have significantly accelerated methylation ages, a calculation of “cellular aging”. Additionally, we identify two differentially methylated regions in the promoters of HOXA4 and MGRN1, in the association between cognitive ability and cumulative neurological pollution exposure. Exploring DNA methylation as a mediator of the association between air pollution exposure and lower cognitive ability may establish a more direct link and thus provide insight into the biological mechanisms involved in the effects of environmental toxins on changes in the central nervous system

Ejaculation: the Process and Characteristics From Start to Finish

Purpose of Review Semen analysis serves as the initial step in the evaluation of male infertility. However, given the difficulty in interpreting abnormal findings, physicians and patients often struggle with understanding the results. In this review, we aim to review the normal physiology of ejaculation and create an accessible resource for interpreting abnormal semen volume, viscosity, liquefaction, pH, appearance, and color. Recent Findings Emerging evidence has revealed that men with genitourinary tract infections have a greater number of seminal leukocytes, which may result in clumping of motile sperm and altered morphology. Hence, these patients may have abnormal sperm parameters secondary to their health status. Recent findings have further characterized the semen liquefaction process, suggesting that increased levels of semenogelin and decreased levels of proteases and plasminogen activators (e.g., urokinase and chymotrypsin) may be associated with the failure of semen to convert to a watery consistency. This article creates a resource which may be referenced when abnormalities in semen analysis are encountered. We offer a comprehensive overview of normal ejaculation physiology and abnormal variants in male ejaculate volume-including aspermia, anejaculation, retrograde ejaculation, and hypo- and hyperspermia-and their potential etiologies. Additionally, we discuss several processes (infection, inflammation, and dysfunction of male sex glands) which may affect semen viscosity, liquefaction, and pH. Finally, our discussion of the potential colors of male ejaculate is meant to reduce the anxiety of both patient and provider. Through a better understanding of the process and varying characteristics of ejaculation, physicians may adequately counsel their patients on abnormal findings and concerns regarding infertility

The Impact of Obesity on Sperm Parameters in Young Adult Males: A Retrospective Study of Sperm Donors

OBJECTIVETo utilize a large cohort of healthy sperm bank donors to evaluate the association between body mass index (BMI) and individual sperm parameters. METHODSSperm parameters from donors across the United States were obtained between 2013-2022. Donors were healthy men aged 18-46 years old. Semen samples were analyzed in a certified lab following guidelines by the World Health Organization. A multivariable interaction model between age, BMI, and sperm parameters was conducted. RESULTSThere were 117,357 sperm donations included in our study. In our sample, 98,397 (83.84%) men were classified as young donors (ages 18-32 years) and 18,960 (16.16%) were classified as old donors (ages 33-46 years). We identified 1,032 (0.88%) men as underweight, 76,635 (65.30%) as normal weight, 36,686 (31.26%) as overweight, and 3,004 (2.56%) as obese. Participants had a median Total Motile Sperm Count (TMSC) of 186 (IQR: 128 million), volume of 3.36 (IQR: 1.82mL), sperm concentration of 56 (IQR: 34 million/mL) and a progressive motility of 59.84% (IQR: 16.95%). Older obese donor had lower TMSC (β = -22.98±4.66, p < 0.001), semen volumes (β = -0.85±0.06, p < 0.001), and progressive motility (β = -3.94±0.56, p < 0.001) compared to younger, healthy weight donors. CONCLUSIONSWe observed lower TMSC, semen volumes, and progressive motility in older obese donors. Although these values are within the normal expected ranges for individual sperm parameters, our ability to detect differences even within this healthy population highlights the importance of maintaining a healthy diet and exercise regimen for preserving high sperm counts

Patient Satisfaction and Long-Term Clinical Outcomes in Adolescent Sub-inguinal Microscopic Varicocelectomy

Introduction and objective: The long-term outcomes of varicocelectomy in adolescents is debated. The aim of this study was to evaluate symptom improvement, hypogonadism, and paternity in those who underwent adolescent sub-inguinal microscopic varicocelectomy. Material and methods: A retrospective chart review was done of adolescents (median=19, interquartile range (IQR)=16-19.75 years) who underwent microscopic varicocelectomy between 2011 and 2021. Demographics, surgical indications, and outcomes were collected, as well as pre- and postoperative hormone levels and semen parameters. A questionnaire was prospectively collected to evaluate orchialgia, paternity, and symptoms of hypogonadism. Descriptive statistics and t-tests were performed, with significance assessed at p-value < 0.05. Results: A total of 46 adolescents were included. Age at the time of diagnosis and surgery was 19 (IQR=16-20) and 19 (IQR= 18-21) years, respectively. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and total testosterone were not affected after surgery. Similarly, semen parameters were preserved after varicocelectomy, with median concentration increasing from 12x10 6 /ml to 16x10 6 /ml but not reaching significance (p=0.272). A total of 26 men completed the questionnaire. The age of responders was 22 (IQR=21-24) years, and the time after having had the varicocelectomy was 36.5 (IQR= 18.25-62.25) months. Orchialgia persisted in five men, and three reported having a recurrence. Two men, who had a preoperative abnormal semen analysis, were actively trying to have children and reported successfully having achieved natural pregnancies. None of the patients reported having hypogonadism, and none were receiving testosterone therapy. Conclusion: Our study suggests that microscopic varicocelectomy in adolescents appears to be a safe and feasible procedure with a low rate of syndrome recurrence and no association with symptoms or biochemical evidence of hypogonadism

U-shaped association between prevalence of secondary hypogonadism and body mass index: a retrospective analysis of men with testosterone deficiency

The prevalence of both obesity and hypogonadism in the United States has increased over the past two decades. While prior studies have shown an association between obesity and secondary hypogonadism-low testosterone and luteinizing hormone-few have used a large enough sample size to determine prevalence at each body mass index class. We aimed to compare rates of secondary hypogonadism among body mass index classes by constructing a retrospective database with men who had their body mass index, morning testosterone and luteinizing hormone levels measured during a visit to a urology clinic at a tertiary academic medical center between 2011-2020. Men previously on testosterone replacement therapy, Clomiphene, or Anastrozole were excluded. Chi-squared analysis was conducted in "R". We found that among the 7211 men studied, 45.7%, 22.6%, and 4.4% were classified as having diagnosis of secondary, primary, and compensated hypogonadism, respectively. We found that obese men and underweight men had increased prevalence of secondary hypogonadism as compared to men with normal body mass index. These findings support the need for routine screening criteria and personalized advice to patients dealing with secondary hypogonadism