1. Sperm epigenetic clock associates with pregnancy outcomes in the general population.
- Author
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Pilsner, J Richard, Saddiki, Hachem, Whitcomb, Brian W, Suvorov, Alexander, Buck Louis, Germaine M, Mumford, Sunni L, Schisterman, Enrique F, Oluwayiose, Oladele A, and Balzer, Laura B
- Subjects
Reproductive Medicine ,Biomedical and Clinical Sciences ,Prevention ,Aging ,Clinical Research ,Contraception/Reproduction ,Reproductive health and childbirth ,Child ,Epigenesis ,Genetic ,Female ,Humans ,Male ,Pregnancy ,Pregnancy Outcome ,Prospective Studies ,Semen ,Spermatozoa ,Time-to-Pregnancy ,sperm epigenetic clock ,aging ,methylation ,infertility ,pregnancy ,machine learning ,Medical and Health Sciences ,Studies in Human Society ,Obstetrics & Reproductive Medicine ,Reproductive medicine - Abstract
Study questionIs sperm epigenetic aging (SEA) associated with probability of pregnancy among couples in the general population?Summary answerWe observed a 17% lower cumulative probability at 12 months for couples with male partners in the older compared to the younger SEA categories.What is known alreadyThe strong relation between chronological age and DNA methylation profiles has enabled the estimation of biological age as epigenetic 'clock' metrics in most somatic tissue. Such clocks in male germ cells are less developed and lack clinical relevance in terms of their utility to predict reproductive outcomes.Study design, size, durationThis was a population-based prospective cohort study of couples discontinuing contraception to become pregnant recruited from 16 US counties from 2005 to 2009 and followed for up to 12 months.Participants/materials, setting, methodsSperm DNA methylation from 379 semen samples was assessed via a beadchip array. A state-of-the-art ensemble machine learning algorithm was employed to predict age from the sperm DNA methylation data. SEA was estimated from clocks derived from individual CpGs (SEACpG) and differentially methylated regions (SEADMR). Probability of pregnancy within 1 year was compared by SEA, and discrete-time proportional hazards models were used to evaluate the relations with time-to-pregnancy (TTP) with adjustment for covariates.Main results and the role of chanceOur SEACpG clock had the highest predictive performance with correlation between chronological and predicted age (r = 0.91). In adjusted discrete Cox models, SEACpG was negatively associated with TTP (fecundability odds ratios (FORs)=0.83; 95% CI: 0.76, 0.90; P = 1.2×10-5), indicating a longer TTP with advanced SEACpG. For subsequent birth outcomes, advanced SEACpG was associated with shorter gestational age (n = 192; -2.13 days; 95% CI: -3.67, -0.59; P = 0.007). Current smokers also displayed advanced SEACpG (P
- Published
- 2022