Sperm DNA methylation profiling in patients with Kallmann syndrome.
Wang. Rongrong R; Li. Xiaogang X; Zhang. Jingdi J; Wang. Xi X; Mao. Jiangfeng J; Feng. Xinxin X; Wang. Siyu S; Li. Yongzhe Y; Wu. Xueyan X; Guo. Ye Y
Key Findings
- KS patients have higher overall sperm DNA methylation, with 4,749 regions altered.
- Affected genes include those involved in neuronal function, GnRH secretion, and key KS genes (CHD7, DCC, IL17RD, NELFA, SEMA3E).
- Spermatogenesis genes such as BRCA1, H3FC3, and HSP90AA1 show methylation changes that correlate with semen parameters.
Practical Outcomes
- Using gonadorelin (synthetic GnRH) to boost hormone levels may lead to lasting epigenetic changes in sperm that could affect fertility. Biohackers should be aware that hormone‑boosting protocols might have hidden impacts on sperm DNA and consider monitoring semen quality if they pursue GnRH therapy.
Summary
The study looked at men with Kallmann syndrome and found that their sperm DNA has many extra chemical tags (methyl groups) compared to healthy men. Some of these changes are linked to genes that control brain development, hormone release, and sperm production. After treatment with GnRH or gonadotropins, the DNA still shows these changes, and they are tied to poorer semen quality.
Abstract
This study aims to comprehensively characterize the DNA methylation profile in the sperm of patients with Kallmann syndrome (KS), providing new insights into the potential epigenetic mechanisms contributing to the pathogenesis of the disease. Sperm samples from patients with KS and healthy controls (HCs) were analyzed for DNA methylation patterns. Differentially methylated regions (DMRs) were identified, and the associated genes underwent enrichment analysis. Spermatogenesis-related genes were screened, analyzed for functional enrichment, and key genes were identified using the STRING database and CytoHubba. Their correlations with semen parameters were then evaluated. This study analyzed six patients with KS and six age-matched HCs, revealing higher DNA methylation in patients with KS. 4,749 DMRs were identified (4,020 hypermethylated, 729 hypomethylated) affecting genes linked to neuronal function, migration, and gonadotropin-releasing hormone (GnRH) secretion. DMRs were also observed in key KS-related genes, including CHD7, DCC, IL17RD, NELFA, and SEMA3E. Moreover, 1,938 spermatogenesis-related genes were identified within the gene body, with significant enrichment in chromosome remodeling pathways. Notably, core spermatogenesis genes such as BRCA1, H3FC3, and HSP90AA1 exhibited significant correlations with semen parameters. This study identified DNA methylation changes in patients with KS after gonadotropin or pulsatile GnRH therapy, reflecting downstream epigenetic consequences of congenital gonadotropin deficiency and its treatment. These alterations are associated with persistent spermatogenic abnormalities, providing a foundation for future studies on epigenetic biomarkers and potential interventions.
Study Information
pubmed
2025
2025-10-18T00:00:00.000Z
10.1530/ec-25-0224