{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T00:56:51Z","timestamp":1784941011801,"version":"3.55.0"},"reference-count":87,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T00:00:00Z","timestamp":1729209600000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Reproduction Devel"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The development of novel non\u2010hormonal male contraceptives represents a pivotal frontier in reproductive health, driven by the need for safe, effective, and reversible contraceptive methods. This comprehensive review explores the genetic underpinnings of male fertility, emphasizing the crucial roles of specific genes and structural variants (SVs) identified through advanced sequencing technologies such as long\u2010read sequencing (LRS). LRS has revolutionized the detection of structural variants and complex genomic regions, offering unprecedented precision and resolution over traditional next\u2010generation sequencing (NGS). Key genetic targets, including those implicated in spermatogenesis and sperm motility, are highlighted, showcasing their potential as non\u2010hormonal contraceptive targets. The review delves into the systematic identification and validation of male reproductive tract\u2010specific genes, utilizing advanced transcriptomics and genomics studies with validation using novel knockout mouse models. We discuss the innovative application of small molecule inhibitors, developed through platforms like DNA\u2010encoded chemistry technology (DEC\u2010Tec), which have shown significant promise in preclinical models. Notable examples include inhibitors targeting serine\/threonine kinase 33 (STK33), soluble adenylyl cyclase (sAC), cyclin\u2010dependent kinase 2 (CDK2), and bromodomain testis associated (BRDT), each demonstrating nanomolar affinity and potential for reversible and specific inhibition of male fertility. This review also honors the contributions of Dr. David L. Garbers whose foundational work has paved the way for these advancements. The integration of genomic, proteomic, and chemical biology approaches, supported by interdisciplinary collaboration, is poised to transform male contraceptive development. Future perspectives emphasize the need for continued innovation and rigorous testing to bring these novel contraceptives from the laboratory to clinical application, promising a new era of male reproductive health management.<\/jats:p>","DOI":"10.1002\/mrd.70000","type":"journal-article","created":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T09:55:17Z","timestamp":1729245317000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Novel Genes of the Male Reproductive System: Potential Roles in Male Reproduction and as Non\u2010hormonal Male Contraceptive Targets"],"prefix":"10.1002","volume":"91","author":[{"given":"Thomas X.","family":"Garcia","sequence":"first","affiliation":[{"name":"Center for Drug Discovery Baylor College of Medicine Houston Texas USA"},{"name":"Department of Pathology &amp; Immunology Baylor College of Medicine Houston Texas USA"},{"name":"Scott Department of Urology Baylor College of Medicine Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin M.","family":"Matzuk","sequence":"additional","affiliation":[{"name":"Center for Drug Discovery Baylor College of Medicine Houston Texas USA"},{"name":"Department of Pathology &amp; Immunology Baylor College of Medicine Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,18]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.12603"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-36119-6"},{"key":"e_1_2_8_4_1","unstructured":"Baylor College of Medicine.2022. \u201cMammalian Reproductive Genetics Database Version 2 (MRGDv2).\u201dhttps:\/\/orit.research.bcm.edu\/MRGDv2."},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1008691"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038-019-0686-1"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.202000499"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21517-5"},{"key":"e_1_2_8_9_1","unstructured":"ClinicalTrials.gov Identifier: NCT03452111.2018. \u201cStudy of Daily Application of Nestorone\u00ae (NES) and Testosterone (T) Combination Gel for Male Contraception.\u201dhttps:\/\/clinicaltrials.gov\/study\/NCT03452111."},{"key":"e_1_2_8_10_1","unstructured":"ClinicalTrials.gov Identifier: NCT03455075.2018. \u201cStudy of Spermatogenesis Suppression With DMAU Alone or With LNG Versus Placebo Alone in Normal Men.\u201dhttps:\/\/clinicaltrials.gov\/study\/NCT03455075."},{"key":"e_1_2_8_11_1","unstructured":"ClinicalTrials.gov Identifier: NCT06094283.2023. \u201cFirst in Human Study Evaluating Single Ascending Oral Doses of YCT\u2010529 in Healthy Males.\u201dhttps:\/\/clinicaltrials.gov\/study\/NCT06094283."},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.686461"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60327-214-8_14"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-023-04714-4"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gau018"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-022-02510-4"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1586\/erp.12.52"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19113-0"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c01731"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.13329"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.6.3415"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1997.4620"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.contraception.2010.03.016"},{"key":"e_1_2_8_24_1","unstructured":"Grand View Research. 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