A Systematic Review of Genotoxicity and Mutagenicity Affecting Reproductive and Neurocognitive Health: Bridging...

This systematic literature review (B-SLR) examines the emerging scholarly consensus on mechanistic linkage between genotoxic exposures and multisystem health dysfunctions. We systematically reviewed 200 peer-reviewed publications from 2021 to 2025 applying SPAR4-SLR protocol with quality appraisal using ROBINS-I adaptation and also performed assessment of publication bias. We have identified trends in genotoxicity research and its causal relationship with reproductive and neurocognitive health outcomes. This novel interdisciplinary approach bridges the traditional siloed research domains of toxicology, genetics, reproductive medicine, and neuroscience. A systematic search strategy using Scopus database and Boolean operators was used at a period of 2020-2025 as well as 2021-2025 to extract articles. SPAR4-SLR protocol was implemented thereby across three stages of assembling, arranging, and assessing. Furthermore, Biblioshiny software (R Language) with quality appraisal (ROBINS-I adapted) and publication bias quantification was performed. This was followed by reporting of thematic mapping, citation network analysis, mechanistic pathway modeling, and validity checks (Scopus vs. Web of Science overlap = 89.5%). This validated coverage adequacy. Bibliometric analysis identified eight major research clusters with distinct maturity profiles: (1) DNA mutations and chromosomal damage (n = 167 papers; h-index 85; mature domain); (2) reprotoxicity and gonadal dysfunction (n = 78; h-index 42; emerging); (3) neurotoxicity and cognitive impairment (n = 89; h-index 51; emerging); (4) transgenerational/epigenetic transmission (n = 34; h-index 28; nascent); (5) bioaccumulation and environmental persistence (n = 96; h-index 59; mature); (6) emerging contaminants (nanoplastics/PFAS/bisphenols) (n = 42; h-index 19; nascent); (7) mechanistic pathway integration (n = 23; h-index 12; nascent); and (8) regulatory and policy applications (n = 8; h-index 4; nascent). A critical knowledge gap was also identified where animal studies dominate, and human epidemiological studies constitute merely 3%. This creates a 20- to 30-year translation lag. The following five high-priority research agendas were identified: (1) comparative potency assessment across emerging contaminants; (2) epigenetic mechanism specificity in transgenerational transmission; (3) mixture/cumulative effects (current literature focuses on single-agent exposures); (4) cost-effective remediation/mitigation strategies; (5) vulnerability characterization for developmentally sensitive populations (gestational windows, critical brain periods, pubertal transition). The research is ready for translation into policy, and the regulatory opportunity closes by 2027-2028. Practical Implications This review provides actionable intelligence for the following five groups: (1) funding agencies-identifies nascent research clusters warranting priority funding; (2) international regulators (OECD, EPA, and EMA)-identifies five critical gaps in current testing guidelines and proposes a unified testing battery, which includes epigenetic endpoints and adverse outcome pathway analysis; (3) occupational health professionals-identifies priority exposure reduction strategies in high-risk sectors; (4) pharmaceutical developers-highlights risk assessment strategies for drug candidates with genotoxic potential; (5) reproductive/pediatric health practitioners-provides evidence synthesis supporting patient counselling on avoidable exposures during critical developmental windows. This integrated mechanistic framework bridges previously siloed research domains to enable coordinated multistakeholder action.