Epigenetic determinants of reproductive potential augment the predictive ability of the semen analysis

F&S science Pub Date : 2023-11-01 DOI:10.1016/j.xfss.2023.09.001

Ryan H. Miller M.S. , Elizabeth A. DeVilbiss Ph.D. , Kristin R. Brogaard Ph.D. , Carter R. Norton , Chad A. Pollard B.S. , Benjamin R. Emery M.S. , Kenneth I. Aston Ph.D. , James M. Hotaling M.D., M.S. , Tim G. Jenkins Ph.D.

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引用次数: 0

Abstract

Objective

To investigate the power of DNA methylation variability in sperm cells in assessing male fertility potential.

Design

Retrospective cohort.

Setting

Fertility care centers.

Patients

Male patients seeking infertility treatment and fertile male sperm donors.

Intervention

None.

Main Outcome Measures

Sperm DNA methylation data from 43 fertile sperm donors were analyzed and compared with the data from 1344 men seeking fertility assessment or treatment. Methylation at gene promoters with the least variable methylation in fertile patients was used to create 3 categories of promoter dysregulation in the infertility treatment cohort: poor, average, and excellent sperm quality.

Results

After controlling for female factors, there were significant differences in intrauterine insemination pregnancy and live birth outcomes between the poor and excellent groups across a cumulative average of 2–3 cycles: 19.4% vs. 51.7% (P=.008) and 19.4% vs. 44.8% (P=.03), respectively. Live birth outcomes from in vitro fertilization, primarily with intracytoplasmic sperm injection, were not found to be significantly different among any of the 3 groups.

Conclusion

Methylation variability in a panel of 1233 gene promoters could augment the predictive ability of semen analysis and be a reliable biomarker for assessing intrauterine insemination outcomes. In vitro fertilization with intracytoplasmic sperm injection appears to overcome high levels of epigenetic instability in sperm.

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生殖潜力的表观遗传学决定因素增强了精液分析的预测能力。

目的：研究精子细胞DNA甲基化变异性在评估男性生育潜力中的作用。设计：回顾性队列。设置：生育护理中心。患者：寻求不孕不育治疗的男性患者和可生育的男性精子捐献者。干预：无。主要结果指标：分析43名可生育精子捐献者的精子DNA甲基化数据，并将其与1344名寻求生育评估或治疗的男性的数据进行比较。在不孕不育治疗队列中，使用可生育患者中甲基化变化最小的基因启动子甲基化来产生3类启动子失调：精子质量差、平均和优秀。结果：在控制了女性因素后，在累计平均2-3个周期内，贫穷组和优秀组在宫内受精妊娠和活产结局方面存在显著差异：分别为19.4%和51.7%（P=0.008）以及19.4%和44.8%（P=0.03）。体外受精（主要是卵浆内精子注射）的活产结果在三组中没有发现显著差异。结论：1233个基因启动子的甲基化变异性可以增强精液分析的预测能力，并成为评估宫内受精结果的可靠生物标志物。卵浆内精子注射的体外受精似乎可以克服精子中高水平的表观遗传不稳定性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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