男性不育症患者的铁生物标志物与精子DNA羟甲基化及累积活产率相关：一项前瞻性研究。

Iron biomarkers in men with infertility are associated with sperm DNA hydroxymethylation and cumulative live birth rates: a prospective study.

作者信息

Raad Georges, Husseiny Fatima, Yarkiner Zalihe, Grandjean Valerie, Bazzi Marwa, Rizk Marilyne, Fakih Fadi, Mourad Youmna, Fakih Chadi

机构信息

Al Hadi Laboratory and medical center, Beirut, Lebanon.

School of Medicine and Medical Sciences, Holy Spirit University of Kaslik, P.O.Box 446, Jounieh, Lebanon.

出版信息

J Transl Med. 2025 Aug 5;23(1):861. doi: 10.1186/s12967-025-06777-9.

DOI:10.1186/s12967-025-06777-9

PMID:40764934

Abstract

BACKGROUND

Pregnancy rates after intracytoplasmic sperm injection (ICSI) could be influenced by sperm quality. Maintaining iron homeostasis is crucial for both sperm quality and the activity of ten-eleven translocation (TET) enzymes. TETs play a role in DNA chemical modifications. However, the impact of iron biomarkers on the sperm DNA chemical modifications and pregnancy outcomes has not been explored. This prospective study aimed to assess whether iron biomarkers in men from infertile couples were associated with global DNA hydroxymethylation (5-hmC) in spermatozoa and cumulative live birth rates (CLBR).

METHODS

Semen and blood samples were collected from 60 infertile men undergoing ICSI cycles with their female partners, alongside medical histories and CLBR outcomes. Serum and seminal fluid levels of iron, transferrin, and total iron binding capacity (TIBC) were measured, and sperm global DNA 5-hmC was quantified using ELISA-based colorimetric assays.

RESULTS

5-hmC levels in spermatozoa were positively correlated with serum iron (R = 0.29; p = 0.04), serum TIBC (R = 0.29; p = 0.04), and seminal fluid iron (R = 0.30; p = 0.04). Univariate analysis showed that a 1 µg/dl increase in seminal fluid or serum iron was associated with a 0.001% rise in 5-hmC (p < 0.05), and each unit increase in serum TIBC led to a 0.001% rise in 5-hmC (p = 0.03). Multivariate regression confirmed that higher serum TIBC levels were significantly associated with increased 5-hmC (%) (p = 0.02). Additionally, multivariate analysis revealed that a 1 µg/dl increase in seminal fluid iron was associated with a 1.016% rise in CLBR (p = 0.0009), while a 1 mg/dl increase in seminal fluid transferrin was associated with a 3.754% decrease in CLBR (p = 0.04).

CONCLUSION

Serum TIBC is positively associated with sperm 5-hmC, while seminal iron shows a positive and transferrin a negative association with CLBR.

摘要

背景

胞浆内单精子注射（ICSI）后的妊娠率可能受精子质量影响。维持铁稳态对精子质量和10-11易位（TET）酶的活性都至关重要。TET酶在DNA化学修饰中起作用。然而，铁生物标志物对精子DNA化学修饰和妊娠结局的影响尚未得到探索。这项前瞻性研究旨在评估不育夫妇男性中的铁生物标志物是否与精子中的整体DNA羟甲基化（5-hmC）和累积活产率（CLBR）相关。

方法

收集了60名接受ICSI周期治疗的不育男性及其女性伴侣的精液和血液样本，以及病史和CLBR结局。测量血清和精液中铁、转铁蛋白和总铁结合力（TIBC）的水平，并使用基于酶联免疫吸附测定的比色法对精子整体DNA 5-hmC进行定量。

结果

精子中的5-hmC水平与血清铁（R = 0.29；p = 0. .04）、血清TIBC（R = 0.29；p = 0.04）和精液铁（R = 0.30；p = 0.04）呈正相关。单因素分析显示，精液或血清铁每增加1μg/dl与5-hmC升高0.001%相关（p < 0.05），血清TIBC每增加一个单位导致5-hmC升高0.001%（p = 0.03）。多因素回归证实，较高的血清TIBC水平与5-hmC（%）增加显著相关（p = 0.02）。此外，多因素分析显示，精液铁每增加1μg/dl与CLBR升高1.016%相关（p = 0.0009），而精液转铁蛋白每增加1mg/dl与CLBR降低3.754%相关（p = 0.04）。