Integrating paternal preconception health and sperm molecular biology into proportionate clinical counseling
- 1Hunan Provincial Key Laboratory of Regional Hereditary Birth Defect Prevention and Control, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University
- 2Hunan Normal University Health Science Center, School of Public Health
- 3Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, Hainan Provincial Clinical Research Center for Thalassemia, Key Laboratory of Reproductive Health Diseases Research and Translation (Hainan Medical University), Ministry of Education, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University
Abstract
Paternal preconception health increasingly appears to modulate reproductive success through alterations in classical semen parameters and spermatozoal molecular architecture. Beyond nuclear genomic transmission, ejaculated spermatozoa convey regulatory chromatin configurations, retained histones, and diverse small non-coding RNA populations to the oocyte. This narrative review synthesizes evidence across metabolic conditions, lifestyle choices, environmental and occupational toxicant exposures, advanced paternal age, thermal insults, and gonadotoxic therapeutic regimens. Furthermore, emerging considerations regarding psychological strain, circadian misalignment, microplastic accumulation, and male reproductive tract microbial dysbiosis are critically evaluated. We critically synthesize preclinical, epidemiological, and interventional data addressing sperm concentration, motility, morphology, spermatozoal DNA integrity, and coupled clinical endpoints. These clinical benchmarks encompass fertilization efficiency, spontaneous miscarriage, and live-birth rates, alongside documented neurodevelopmental and cardiometabolic trajectories in offspring. Although observational studies link various paternal exposures to impaired semen quality, substantial heterogeneity persists across diverse patient cohorts. Crucially, direct empirical evidence demonstrating that exposure-associated spermatozoal molecular alterations survive post-fertilization reprogramming to cause adverse human phenotypes remains lacking. Postulated mechanistic axes include oxidative stress, systemic inflammation, endocrine disruption, and altered epididymal vesicular signaling, despite incomplete clinical validation. Nevertheless, the 74–90-day window of spermatogenesis and epididymal transit provides an actionable timeline for preconception risk mitigation, rather than a proven “epigenetic reset.” We therefore propose an evidence-informed clinical framework delineating guideline-endorsed baseline evaluations and low-risk lifestyle counseling from investigational assays and commercial claims. Importantly, this framework does not assume that paternal exposure-associated sperm epigenetic alterations persist after fertilization, are transmitted across generations, or determine offspring health.
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BibTeX
@article{liu2026integrating,
title = {{Integrating paternal preconception health and sperm molecular biology into proportionate clinical counseling}},
author = {Jing Liu and Lulu Qin and Bang Liu and Mengmei Lv and Jingyu Fan and Dai Zhou},
journal = {Frontiers in Endocrinology},
year = {2026},
month = nov,
doi = {10.3389/fendo.2026.1970976},
url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.1970976/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Integrating paternal preconception health and sperm molecular biology into proportionate clinical counseling
AU - Jing Liu
AU - Lulu Qin
AU - Bang Liu
AU - Mengmei Lv
AU - Jingyu Fan
AU - Dai Zhou
PY - 2026
DA - 2026/11/02
JO - Frontiers in Endocrinology
DO - 10.3389/fendo.2026.1970976
UR - https://www.frontiersin.org/articles/10.3389/fendo.2026.1970976/full
AB - Paternal preconception health increasingly appears to modulate reproductive success through alterations in classical semen parameters and spermatozoal molecular architecture. Beyond nuclear genomic transmission, ejaculated spermatozoa convey regulatory chromatin configurations, retained histones, and diverse small non-coding RNA populations to the oocyte. This narrative review synthesizes evidence across metabolic conditions, lifestyle choices, environmental and occupational toxicant exposures, advanced paternal age, thermal insults, and gonadotoxic therapeutic regimens. Furthermore, emerging considerations regarding psychological strain, circadian misalignment, microplastic accumulation, and male reproductive tract microbial dysbiosis are critically evaluated. We critically synthesize preclinical, epidemiological, and interventional data addressing sperm concentration, motility, morphology, spermatozoal DNA integrity, and coupled clinical endpoints. These clinical benchmarks encompass fertilization efficiency, spontaneous miscarriage, and live-birth rates, alongside documented neurodevelopmental and cardiometabolic trajectories in offspring. Although observational studies link various paternal exposures to impaired semen quality, substantial heterogeneity persists across diverse patient cohorts. Crucially, direct empirical evidence demonstrating that exposure-associated spermatozoal molecular alterations survive post-fertilization reprogramming to cause adverse human phenotypes remains lacking. Postulated mechanistic axes include oxidative stress, systemic inflammation, endocrine disruption, and altered epididymal vesicular signaling, despite incomplete clinical validation. Nevertheless, the 74–90-day window of spermatogenesis and epididymal transit provides an actionable timeline for preconception risk mitigation, rather than a proven “epigenetic reset.” We therefore propose an evidence-informed clinical framework delineating guideline-endorsed baseline evaluations and low-risk lifestyle counseling from investigational assays and commercial claims. Importantly, this framework does not assume that paternal exposure-associated sperm epigenetic alterations persist after fertilization, are transmitted across generations, or determine offspring health.
SN - 1664-2392
ER -