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Testicular function is temperature dependent, and in both man and mouse the position of the testes in the scrotum ensures that they are kept at between 2 and 8\u200a\u00b0C below core body temperature. We used a mouse model to investigate the impact of a single, transient, mild, scrotal heat stress (38, 40 or 42\u200a\u00b0C for 30\u200amin) on testicular function, sperm DNA integrity and embryo survival. We detected temperature-dependent changes in testicular architecture, number of apoptotic cells and a significant reduction in testis weight 7 and 14 days after heat stress at 42\u200a\u00b0C. We report for the first time that DNA strand breaks (\u03b3-H2AX-positive foci) were present in spermatocytes recovered from testes subjected to 40 or 42\u200a\u00b0C. Fertility of heat-stressed males was tested 23\u201328 d after treatment (sperm at this time would have been spermatocytes at time of heating). Paternal heat stress at 42\u200a\u00b0C resulted in reduced pregnancy rate, placental weight and litter size; pregnancies from the 40\u200a\u00b0C group had increased resorptions at e14.5. Abnormalities in embryonic development were detected at e3.5 and in vitro fertilisation with sperm recovered 16\u200ah or 23 d after scrotal stress at 42\u200a\u00b0C revealed a block in development between the 4-cell and blastocyst stages. This study has provided evidence of temperature-dependent effects on germ cell DNA integrity and highlighted the importance of an intact paternal genome for normal embryo development.<\/jats:p>","DOI":"10.1530\/rep-08-0036","type":"journal-article","created":{"date-parts":[[2008,4,11]],"date-time":"2008-04-11T11:48:19Z","timestamp":1207914499000},"page":"73-84","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-11","source":"Crossref","is-referenced-by-count":241,"title":["A single, mild, transient scrotal heat stress causes DNA damage, subfertility and impairs formation of blastocysts in mice"],"prefix":"10.1093","volume":"136","author":[{"given":"Catriona","family":"Paul","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison A","family":"Murray","sequence":"additional","affiliation":[{"name":"MRC Human Reproductive Sciences Unit Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK and 1Centre for Integrative Physiology University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norah","family":"Spears","sequence":"additional","affiliation":[{"name":"MRC Human Reproductive Sciences Unit Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK and 1Centre for Integrative Physiology University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippa T K","family":"Saunders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,7,1]]},"reference":[{"key":"2026010712481848800_bib1","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1530\/rep.1.00531","article-title":"Impact of a mild scrotal heat stress on DNA integrity in murine spermatozoa","volume":"129","author":"Banks","year":"2005","journal-title":"Reproduction"},{"key":"2026010712481848800_bib2","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1038\/311374a0","article-title":"Role of paternal and maternal genomes in mouse development","volume":"311","author":"Barton","year":"1984","journal-title":"Nature"},{"key":"2026010712481848800_bib3","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/978-1-4684-5913-5_3","article-title":"Effects of elevated temperature on the epididymis and testis: experimental studies","volume":"286","author":"Bedford","year":"1991","journal-title":"Advances in Experimental Medicine and Biology"},{"key":"2026010712481848800_bib4","first-page":"86","article-title":"The culture of mouse embryos in vitro","volume-title":"Methods in Mammalian Embryology","author":"Biggers","year":"1971"},{"key":"2026010712481848800_bib5","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1016\/j.theriogenology.2006.06.011","article-title":"Genetic variation in fertility of heat-stressed male mice","volume":"66","author":"Cammack","year":"2006","journal-title":"Theriogenology"},{"key":"2026010712481848800_bib6","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1007\/s10495-005-0813-7","article-title":"Apoptosis and cell removal in the cryptorchid rat testis","volume":"10","author":"Chaki","year":"2005","journal-title":"Apoptosis"},{"key":"2026010712481848800_bib7","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1002\/1097-0142(19900501)65:9<1903::AID-CNCR2820650905>3.0.CO;2-#","article-title":"Testicular dysfunction after cyclophosphamide-vincristine-procarbazine-prednisolone chemotherapy for advanced Hodgkin's disease. 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