{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:31:40Z","timestamp":1791977500038,"version":"4.4.0"},"reference-count":50,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T00:00:00Z","timestamp":1708041600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Environmental Health Sciences, National Institutes of Health (R01 ES028298; PI: J.R.P.)"},{"name":"Robert J. Sokol, MD Endowed Chair of Molecular Obstetrics and Gynecology (J.R.P.)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>The well-documented relationship between chronological age and the sperm methylome has allowed for the construction of epigenetic clocks that estimate the biological age of sperm based on DNA methylation, which we previously termed sperm epigenetic age (SEA). Our lab demonstrated that SEA is positively associated with the time taken to achieve pregnancy; however, its relationship with semen parameters is unknown. A total of 379 men from the Longitudinal Investigation of Fertility and Environment (LIFE) study, a non-clinical cohort, and 192 men seeking fertility treatment from the Sperm Environmental Epigenetics and Development Study (SEEDS) were included in the study. Semen analyses were conducted for both cohorts, and SEA was previously generated using a machine learning algorithm and DNA methylation array data. Association analyses were conducted via multivariable linear regression models adjusting for BMI and smoking status. We found that SEA was not associated with standard semen characteristics in SEEDS and LIFE cohorts. However, SEA was significantly associated with higher sperm head length and perimeter, the presence of pyriform and tapered sperm, and lower sperm elongation factor in the LIFE study (p &lt; 0.05). Based on our results, SEA is mostly associated with defects in sperm head morphological factors that are less commonly evaluated during male infertility assessments. SEA shows promise to be an independent biomarker of sperm quality to assess male fecundity.<\/jats:p>","DOI":"10.3390\/cimb46020101","type":"journal-article","created":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T08:02:17Z","timestamp":1708070537000},"page":"1567-1578","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Associations between Sperm Epigenetic Age and Semen Parameters: An Evaluation of Clinical and Non-Clinical Cohorts"],"prefix":"10.3390","volume":"46","author":[{"given":"Savni","family":"Sawant","sequence":"first","affiliation":[{"name":"C.S. Mott Center for Human Growth and Development, Department of Obstetrics and Gynecology, School of Medicine, Wayne State University, Detroit, MI 48201, USA"},{"name":"Department of Biochemistry, Microbiology, Immunology, School of Medicine, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oladele A.","family":"Oluwayiose","sequence":"additional","affiliation":[{"name":"C.S. Mott Center for Human Growth and Development, Department of Obstetrics and Gynecology, School of Medicine, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Nowak","sequence":"additional","affiliation":[{"name":"C.S. Mott Center for Human Growth and Development, Department of Obstetrics and Gynecology, School of Medicine, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"DruAnne L.","family":"Maxwell","sequence":"additional","affiliation":[{"name":"C.S. Mott Center for Human Growth and Development, Department of Obstetrics and Gynecology, School of Medicine, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Houle","sequence":"additional","affiliation":[{"name":"C.S. Mott Center for Human Growth and Development, Department of Obstetrics and Gynecology, School of Medicine, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda L.","family":"Paskavitz","sequence":"additional","affiliation":[{"name":"C.S. Mott Center for Human Growth and Development, Department of Obstetrics and Gynecology, School of Medicine, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hachem","family":"Saddiki","sequence":"additional","affiliation":[{"name":"Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6892-9244","authenticated-orcid":false,"given":"Ricardo P.","family":"Bertolla","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Urology, Human Reproduction Section, S\u00e3o Paulo Federal University, S\u00e3o Paulo 04024-001, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Richard","family":"Pilsner","sequence":"additional","affiliation":[{"name":"C.S. Mott Center for Human Growth and Development, Department of Obstetrics and Gynecology, School of Medicine, Wayne State University, Detroit, MI 48201, USA"},{"name":"Institute of Environmental Health Sciences, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,16]]},"reference":[{"key":"ref_1","unstructured":"WHO (2023). Infertility Prevalence Estimates, 1990\u20132021."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0140-6736(20)32667-2","article-title":"Male infertility","volume":"397","author":"Agarwal","year":"2021","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Boitrelle, F., Shah, R., Saleh, R., Henkel, R., Kandil, H., Chung, E., Vogiatzi, P., Zini, A., Arafa, M., and Agarwal, A. (2021). The Sixth Edition of the WHO Manual for Human Semen Analysis: A Critical Review and SWOT Analysis. 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