An assessment of alterations to human sperm methylation patterns in coronavirus disease 2019 infected and healthy control males.

OBJECTIVE: To determine whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection affects male reproductive health, considering the many potential factors that contribute to declines in male fertility on a semiglobal scale. DESIGN: In total, 64 human semen samples-32 treatment and 32 control-were laboratory processed and bioinformatically analyzed to assess differences in DNA methylation patterns. Implementing multiple bioinformatic tools, the analyses conducted will elicit between-group differences with respect to epigenetic age, epigenetic instability, semiglobal, and regional methylation, in addition to methylation patterns as a function of time since infection. SETTING: University hospital. PATIENTS: The study cohort of 64 individuals was drawn from a larger population of 94 volunteer participants recruited at the Human Reproduction Center at the Clinical Hospital of the Ribeirao Preto Medical School-University of São Paulo between June 2021 and January 2022 as well as in accordance with the ethical guidelines established by the Declaration of Helsinki. INTERVENTION: Exposure to SARS-CoV-2. MAIN OUTCOME MEASURE(S): Effects on male reproductive health were reported as differences in DNA methylation measured using an array. Mean ß values at key regulatory loci for human spermatocytes were analyzed and compared between groups. Further analysis of ß values using epigenetic age, instability, semiglobal, and regional methylation tools provided an analysis with substantial breadth and depth. RESULTS: In all analyses, there were no differences between groups. Considering these results, it can be inferred that infection with SARS-CoV-2 does not alter the epigenome of human spermatocytes in significant and/or persistent ways. Tangentially, these data also suggest that human male reproductive health is minimally altered by the virus, or that it is altered in a way that is independent of epigenetic programming. CONCLUSION: Infection with SARS-CoV-2 has been reportedly associated with alterations in male fertility. This study asserts that such alterations do not have an epigenetic basis but are likely a result of concomitant symptomatology, i.e., fever and inflammation. Across the multiple bioinformatic analyses conducted, the results of this test did not detect any differences in DNA methylation patterns between coronavirus disease 2019 and noncoronavirus disease semen donor groups.

Altered Epigenetic Profiles in the Placenta of Preeclamptic and Intrauterine Growth Restriction Patients.

Intrauterine growth restriction (IUGR) and preeclampsia (PE) are placental pathologies known to complicate pregnancy and cause neonatal disorders. To date, there is a limited number of studies on the genetic similarity of these conditions. DNA methylation is a heritable epigenetic process that can regulate placental development. Our objective was to identify methylation patterns in placental DNA from normal, PE and IUGR-affected pregnancies. DNA was extracted, and bisulfite was converted, prior to being hybridized for the methylation array. Methylation data were SWAN normalized and differently methylated regions were identified using applications within the USEQ program. UCSC's Genome browser and Stanford's GREAT analysis were used to identify gene promoters. The commonality among affected genes was confirmed by Western blot. We observed nine significantly hypomethylated regions, two being significantly hypomethylated for both PE and IGUR. Western blot confirmed differential protein expression of commonly regulated genes. We conclude that despite the uniqueness of methylation profiles for PE and IUGR, the similarity of some methylation alterations in pathologies could explain the clinical similarities observed with these obstetric complications. These results also provide insight into the genetic similarity between PE and IUGR and suggest possible gene candidates plausibly involved in the onset of both conditions.

Efficacy of collagenase Clostridium histolyticum in men with congenital penile curvature.

BACKGROUND: Collagenase Clostridium histolyticum (CCH) has been proven effective in multiple subpopulations of PD men; however, no studies have evaluated its role with congenital penile curvature (CPC). AIM: To evaluate the safety and efficacy of CCH in men with CPC. METHODS: A prospective registry was queried of men undergoing CCH injections at our institution. Beginning in 2016, CCH was administered to CPC men using a similar protocol to PD. A comparative analysis was performed between cohorts to evaluate the safety and efficacy of therapy. OUTCOMES: Objective measures included penile length and curvature, while subjective outcomes included standardized (International Index of Erectile Function and Peyronie's Disease Questionnaire) and non-standardized assessments. Curvature outcomes were categorized as follows: 1 - included all men, with the most recent assessment considered final, and 2 - only men who had completed eight CCH injections or stopped early due to satisfaction. RESULTS: From 2014 to Oct 2021, a total of 453 men (408 PD, 45 CPC) underwent one or more CCH injections. In comparing cohorts, CPC men were younger (33 vs 58 years, p<0.0001), had lesser baseline curvatures (52.5 vs 65°, p<0.01), more ventral curves (25.7 vs 9.2%, p<0.01), and longer penile lengths (12.5 vs 12.0 cm, p=0.04). Following treatment, both cohorts experienced similar curvature improvements. Specifically, PD men experienced 20-25° or 33-35% improvements depending on definition compared to 25-30° or 40-50% in CPC men (all p-values >0.05). CPC and PD men also demonstrated similar changes on standardized questionnaires, with the exception of the Psychological and Physical subdomain, which was more improved in CPC men (-11 vs -4, p<0.01). Baseline curvature was positively correlated with greater absolute (degree) and relative (percent) improvements. Adverse events were similar between groups after controlling for confounders. CLINICAL IMPLICATIONS: CCH may be safely and effectively administered in men with CPC. These data provide the first evidence for the efficacy of a non-surgical therapeutic option in this cohort. STRENGTHS AND LIMITATIONS: Strengths - large, prospective series with standardized assessments; Limitations - non-randomized study, short-term follow-up, and lack of standardized method to differentiate CPC from PD. CONCLUSIONS: CCH may be safely and effectively administered to men with CPC, with similar success rates compared to PD. Increasing curvature was associated with greater absolute (degree) and relative (percent) improvements, supporting the role for CCH in men with mild, moderate, or severe curvatures. External validation is warranted prior to routine implementation.