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This is first seen 1\u20132\u2009weeks post heat stress, peaking 4\u20135\u2009weeks thereafter. The higher the temperature, or the longer the duration of heat, the more pronounced germ cell loss becomes, within extreme cases this leads to azoospermia. The second, and often underappreciated impact of testicular hyperthermia is the production of poor\u2010quality spermatozoa. Typically, those cells that survive hyperthermia develop into morphologically abnormal and poorly motile spermatozoa. While both apoptotic and non\u2010apoptotic pathways are known to contribute to hyperthermic germ cell loss, the mechanisms leading to formation of poor\u2010quality sperm remain unclear.<\/jats:p><jats:p>Mechanistically, it is unlikely that testicular hyperthermia affects messenger RNA (mRNA) abundance, as a comparison of four different mammalian studies shows no consistent single gene changes. Using available evidence, we propose two novel models to explain how testicular hyperthermia impairs sperm formation. Our first model suggests aberrant alternative splicing, while the second model proposes a loss of RNA repression. Importantly, neither model requires consistent changes in RNA species.<\/jats:p>","DOI":"10.1111\/brv.12921","type":"journal-article","created":{"date-parts":[[2022,11,22]],"date-time":"2022-11-22T10:40:04Z","timestamp":1669113604000},"page":"603-622","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Testicular heat stress, a historical perspective and two postulates for why male germ cells are heat sensitive"],"prefix":"10.1111","volume":"98","author":[{"given":"Benjamin R.","family":"Robinson","sequence":"first","affiliation":[{"name":"Faculty of Science and Faculty of Health and Medicine University of Newcastle  Callaghan NSW 2308 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob K.","family":"Netherton","sequence":"additional","affiliation":[{"name":"Faculty of Science and Faculty of Health and Medicine University of Newcastle  Callaghan NSW 2308 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel A.","family":"Ogle","sequence":"additional","affiliation":[{"name":"Faculty of Science and Faculty of Health and Medicine University of Newcastle  Callaghan NSW 2308 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3933-9784","authenticated-orcid":false,"given":"Mark A.","family":"Baker","sequence":"additional","affiliation":[{"name":"Faculty of Science and Faculty of Health and Medicine University of Newcastle  Callaghan NSW 2308 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,11,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.4161\/oxim.1.1.6843"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-58923-6"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplegacy.1941.132.3.791"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001899"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1530\/REP-15-0562"},{"issue":"2","key":"e_1_2_8_7_1","first-page":"93","article-title":"The sequential appearance of sperm abnormalities after scrotal insulation or dexamethasone treatment in bulls","volume":"35","author":"Barth A. 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