{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T16:43:28Z","timestamp":1786725808830,"version":"build-2736575974"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>\n                    A\n                    <jats:sc>BSTRACT<\/jats:sc>\n                  <\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Environmental exposures to endocrine-disrupting chemicals have emerged as significant risk factors underlying the etiopathogenesis of hypospadias, yet molecular mechanisms linking environmental factors to phenotypic outcomes remain poorly understood. This systematic review aimed to evaluate epigenetic alterations in human subjects with hypospadias and identify DNA methylation patterns contributing to the disease etiopathogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods:<\/jats:title>\n                    <jats:p>A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Comprehensive literature searches were performed in PubMed\/MEDLINE in June 2025 using terms including hypospadias, epigenetics, DNA methylation, and related concepts. Two reviewers independently conducted study selection, data extraction, and quality assessment using an adapted Joanna Briggs Institute\u2019s (JBI) Critical appraisal checklist.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Eight studies (2011\u20132024) involving 182 patients and 146 controls from diverse geographical locations met the inclusion criteria. Various methodologies were employed including genome-wide methylation profiling, methylated-site display-amplified fragment length polymorphism, and quantitative RT-PCR. Key findings included: (1) hormone signaling dysregulation with androgen receptor downregulation and estrogen receptor alpha upregulation; (2) differential methylation patterns in genes regulating smooth muscle function, lipid transport, and developmental signaling; (3) inverse correlation between differentially methylated regions and phenotypic severity; (4) environmental factor associations with xenobiotic metabolism gene upregulation; and (5) tissue-specific epigenetic signatures with potential as noninvasive biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Epigenetic regulation represents a critical dimension in hypospadias etiopathogenesis. DNA methylation alterations are linked to disrupted hormonal signaling, developmental pathways, and environmental exposures. Novel candidate genes and tissue-specific signatures offer potential biomarkers and therapeutic targets. These findings provide translational insights for early diagnosis, prevention strategies, and targeted interventions, warranting validation through larger multicentric cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/jiaps.jiaps_287_25","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T20:00:20Z","timestamp":1778011220000},"page":"418-426","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Epigenetic Signatures in Hypospadias: Systematic Review"],"prefix":"10.4103","volume":"31","author":[{"given":"Jyoti","family":"Sharma","sequence":"first","affiliation":[{"name":"Department of Paediatric Surgery, All India Institute of Medical Sciences, New Delhi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prabudh","family":"Goel","sequence":"additional","affiliation":[{"name":"Department of Paediatric Surgery, All India Institute of Medical 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