Miller Ryan H, DeVilbiss Elizabeth A, Brogaard Kristin R, Norton Carter R, Pollard Chad A, Emery Benjamin R, Aston Kenneth I, Hotaling James M, Jenkins Tim G
Inherent Biosciences, Salt Lake City, Utah.
Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.
F S Sci. 2023 Nov;4(4):279-285. doi: 10.1016/j.xfss.2023.09.001. Epub 2023 Sep 13.
To investigate the power of DNA methylation variability in sperm cells in assessing male fertility potential.
Retrospective cohort.
Fertility care centers.
Male patients seeking infertility treatment and fertile male sperm donors.
None.
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.
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.
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.
研究精子细胞中DNA甲基化变异性在评估男性生育潜力方面的作用。
回顾性队列研究。
生育护理中心。
寻求不孕治疗的男性患者和有生育能力的男性精子捐献者。
无。
分析了43名有生育能力的精子捐献者的精子DNA甲基化数据，并与1344名寻求生育评估或治疗的男性的数据进行了比较。在生育能力正常的患者中甲基化变异最小的基因启动子处的甲基化情况，被用于在不孕治疗队列中创建3类启动子失调情况：精子质量差、中等和优秀。
在控制女性因素后，在累计平均2至3个周期内，精子质量差和优秀的两组之间，宫内人工授精的妊娠和活产结局存在显著差异：分别为19.4%对51.7%（P = 0.008）和19.4%对44.8%（P = 0.03）。体外受精（主要是卵胞浆内单精子注射）的活产结局在3组中的任何一组之间均未发现显著差异。
1233个基因启动子的甲基化变异性可增强精液分析的预测能力，并成为评估宫内人工授精结局的可靠生物标志物。卵胞浆内单精子注射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。
