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Defects in sperm head shaping frequently lead to teratozoospermia concomitant with oligozoospermia and asthenozoospermia, but the pathogenic mechanism underlying sperm head shaping, and its role in male infertility, remain poorly understood.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>OBJECTIVE AND RATIONALE<\/jats:title>\n                  <jats:p>This review aims to summarize the mechanism underlying sperm head shaping, reveal the relationship between gene defects associated with sperm head shaping and male infertility in humans and mice, and explore potential clinical improvements in ICSI treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>SEARCH METHODS<\/jats:title>\n                  <jats:p>We searched the PubMed database for articles published in English using the keyword \u2018sperm head shaping\u2019 in combination with the following terms: \u2018acrosome formation\u2019, \u2018proacrosomal vesicles (PAVs)\u2019, \u2018manchette\u2019, \u2018perinuclear theca (PT)\u2019, \u2018chromatin condensation\u2019, \u2018linker of nucleoskeleton and cytoskeleton (LINC) complex\u2019, \u2018histone-to-protamine (HTP) transition\u2019, \u2018male infertility\u2019, \u2018ICSI\u2019, and \u2018artificial oocyte activation (AOA)\u2019. The selected publications until 1 August 2024 were critically summarized, integrated, and thoroughly discussed, and the irrelevant literature were excluded.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>OUTCOMES<\/jats:title>\n                  <jats:p>A total of 6823 records were retrieved. After careful screening, integrating relevant literature, and excluding articles unrelated to the topic of this review, 240 articles were ultimately included in the analysis. Firstly, we reviewed the important molecular events and structures integral to sperm head shaping, including PAV formation to fusion, acrosome attachment to the nucleus, structure and function of the manchette, PT, chromatin condensation, and HTP transition. Then, we set forth human male infertility associated with sperm head shaping and identified genes related to sperm head shaping resulting in teratozoospermia concomitant with oligozoospermia and asthenozoospermia. Finally, we summarized the outcomes of ICSI in cases of male infertility resulting from mutations in the genes associated with sperm head shaping, as well as the ICSI outcomes through AOA for infertile men with impaired sperm head.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>WIDER IMPLICATIONS<\/jats:title>\n                  <jats:p>Understanding the molecular mechanisms of sperm head shaping and its relationship with human male infertility holds profound clinical implications, which may contribute to risk prediction, genetic diagnosis, and the potential treatment of human male infertility.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/humupd\/dmaf003","type":"journal-article","created":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T00:23:31Z","timestamp":1741134211000},"page":"307-332","source":"Crossref","is-referenced-by-count":15,"title":["Molecular insights into sperm head shaping and its role in human male fertility"],"prefix":"10.1093","volume":"31","author":[{"given":"Jiaxin","family":"He","sequence":"first","affiliation":[{"name":"Institute of Reproduction and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Xiangya Basic Medical Sciences, Central South University , Changsha, Hunan,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinle","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Reproduction and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Xiangya Basic Medical Sciences, Central South University , Changsha, Hunan,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Tan","sequence":"additional","affiliation":[{"name":"Institute of Reproduction and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Xiangya Basic Medical Sciences, Central South University , Changsha, Hunan,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Reproduction and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Xiangya Basic Medical Sciences, Central South University , Changsha, Hunan,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilan","family":"Su","sequence":"additional","affiliation":[{"name":"Institute of Reproduction and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Xiangya Basic Medical Sciences, Central South University , Changsha, Hunan,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ge","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Reproduction and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Xiangya Basic Medical Sciences, Central South University , Changsha, Hunan,","place":["China"]},{"name":"Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA , Changsha, Hunan,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8359-4654","authenticated-orcid":false,"given":"Yue-Qiu","family":"Tan","sequence":"additional","affiliation":[{"name":"Institute of Reproduction and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Xiangya Basic Medical Sciences, Central South University , Changsha, Hunan,","place":["China"]},{"name":"Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA , Changsha, 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