The impact of zinc and folic acid supplementation on sperm DNA methylation: results from the folic acid and zinc supplementation randomized clinical trial (FAZST)

被引:16
作者
Jenkins, Tim [1 ,2 ,3 ]
Aston, Kenneth [1 ,3 ]
Carrell, Douglas [1 ,3 ,4 ]
DeVilbiss, Elizabeth [5 ]
Sjaarda, Lindsey [5 ]
Perkins, Neil [6 ]
Mills, James L. [5 ]
Chen, Zhen [6 ]
Sparks, Amy [7 ]
Clemons, Traci [8 ]
Chaney, Kayla [8 ]
Peterson, C. Matthew [9 ]
Emery, Benjamin [3 ]
Hotaling, Jim [1 ]
Johnstone, Erica [9 ]
Schisterman, Enrique [10 ]
Mumford, Sunni L. [5 ]
机构
[1] Univ Utah, Sch Med, Dept Surg, Div Urol, Salt Lake City, UT USA
[2] Brigham Young Univ, Dept Cell Biol & Physiol, Provo, UT 84602 USA
[3] Univ Utah, Sch Med, Androl & IVF Labs, Salt Lake City, UT USA
[4] Univ Utah, Sch Med, Dept Human Genet, Salt Lake City, UT 84132 USA
[5] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, Bethesda, MD 20892 USA
[6] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, Bethesda, MD USA
[7] Ctr Adv Reprod Care, IVF & Androl Labs, Iowa City, IA USA
[8] Emmes Co LLC, Rockville, MD USA
[9] Univ Utah, Sch Med, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Salt Lake City, UT 84132 USA
[10] Univ Penn, Perelman Sch Med, Dept Biostat Epidemiol & Informat, Philadelphia, PA 19104 USA
基金
美国国家卫生研究院;
关键词
DNA methylation; sperm; folic acid; zinc; epigenetics; METHYLOME;
D O I
10.1016/j.fertnstert.2021.09.009
中图分类号
R71 [妇产科学];
学科分类号
100211 ;
摘要
Objective: To determine if 6-month folic acid (5 mg) and zinc (30 mg) supplementation impacts sperm DNA methylation patterns. Design: A multicenter, double-blind, block randomized, placebo-controlled trial titled "The Folic Acid and Zinc Supplementation Trial (FAZST)." Setting: Infertility care centers. Patient(s): Male partners (18 years and older) from heterosexual couples (female partners aged 18-45 years) seeking fertility treatment were recruited. Intervention(s): Men were randomized 1:1 to receive folic acid (5 mg) and elemental zinc (30 mg) (n = 713) or a matching placebo (n = 757) daily for 6 months. Main Outcome Measure(s): Sperm DNA methylation was analyzed using the EPIC methylation array (Illumina) at 6 months. Differential sperm DNA methylation was assessed at multiple levels (regional, single cytosine phosphate guanine, etc.). We additionally assessed the impact of supplementation on epigenetic age. Result(s): No significant differences were identified between the treatment and placebo groups although some trends appeared to be present. To determine if these trends were noteworthy, we implemented various permutations and found that the patterns we identified were no more than would be expected by random chance. Conclusion(s): The data presented here strongly suggest that this supplementation regimen is not effective at altering sperm DNA methylation. These data comport well with previous findings from the FAZST study that found no impact of supplementation on basic semen analysis parameters or live birth. (C) 2021 by American Society for Reproductive Medicine.)
引用
收藏
页码:75 / 85
页数:11
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