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Additionally, high-fat (HF) diet is a risk factor for reproductive disorders in males. In this study, we tested the hypothesis that prenatal exposure to a physiologically relevant dose of DEHP in conjunction with HF diet synergistically impacts reproductive function and fertility in male offspring. Female mice were fed a control or HF diet 7\u00a0days prior to mating and until their litters were weaned on postnatal day 21. Pregnant dams were exposed to DEHP or vehicle from gestational day 10.5 until birth. The male offspring\u2019s gross phenotype, sperm quality, serum hormonal levels, testicular histopathology, and testicular gene expression pattern were analyzed. Male mice born to dams exposed to DEHP + HF had smaller testes, epididymides, and shorter anogenital distance compared with those exposed to HF or DEHP alone. DEHP + HF mice had lower sperm concentration and motility compared with DEHP mice. Moreover, DEHP + HF mice had more apoptotic germ cells, fewer Leydig cells, and lower serum testosterone levels than DEHP mice. Furthermore, testicular mRNA expression of Dnmt1 and Dnmt3a was two to eight-fold higher than in DEHP mice by qPCR, suggesting that maternal HF diet and prenatal DEHP exposure additively impact gonadal function by altering the degree of DNA methylation in the testis. These results suggest that the combined exposure to DEHP and high-fat synergistically impairs reproductive function in male offspring, greater than exposure to DEHP or HF diet\u00a0alone.<\/jats:p>","DOI":"10.1093\/biolre\/ioae029","type":"journal-article","created":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T17:36:31Z","timestamp":1708536991000},"page":"1025-1037","source":"Crossref","is-referenced-by-count":4,"title":["Prenatal exposure to Di(2-ethylhexyl) phthalate and high-fat diet synergistically disrupts gonadal function in male mice"],"prefix":"10.1093","volume":"110","author":[{"given":"Radwa","family":"Barakat","sequence":"first","affiliation":[{"name":"Department of Comparative Biosciences , College of Veterinary Medicine, , Urbana, IL , USA"},{"name":"University of Illinois , College of Veterinary Medicine, , Urbana, IL , USA"},{"name":"Department of Toxicology and Forensic Medicine , Faculty of Veterinary Medicine, , Qalyubia , Egypt"},{"name":"Benha University , Faculty of Veterinary Medicine, , Qalyubia , Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po-Ching Patrick","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Comparative Biosciences , College of Veterinary Medicine, , Urbana, IL , USA"},{"name":"University of Illinois , College of Veterinary Medicine, , Urbana, IL , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Bunnell","sequence":"additional","affiliation":[{"name":"Department of Comparative Biosciences , College of Veterinary Medicine, , Urbana, IL , USA"},{"name":"University of Illinois , College of Veterinary Medicine, , Urbana, IL , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Eun","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Comparative Biosciences , College of Veterinary Medicine, , Urbana, IL , USA"},{"name":"University of Illinois , College of Veterinary Medicine, , Urbana, IL , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saniya","family":"Rattan","sequence":"additional","affiliation":[{"name":"Department of Comparative Biosciences , College of Veterinary Medicine, , Urbana, IL , USA"},{"name":"University of Illinois , College of Veterinary Medicine, , Urbana, IL , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyrus","family":"Arnieri","sequence":"additional","affiliation":[{"name":"Department of Comparative Biosciences , College of Veterinary Medicine, , Urbana, IL , USA"},{"name":"University of Illinois , College of Veterinary Medicine, , Urbana, IL , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jodi A","family":"Flaws","sequence":"additional","affiliation":[{"name":"Department of Comparative Biosciences , College of Veterinary Medicine, , Urbana, IL , USA"},{"name":"University of Illinois , College of Veterinary Medicine, , Urbana, IL , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"CheMyong J","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Comparative Biosciences , College of Veterinary Medicine, , Urbana, IL , USA"},{"name":"University of Illinois , College of Veterinary Medicine, , Urbana, IL , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,2,21]]},"reference":[{"key":"2024051505515468600_ref1","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1007\/s10815-023-02859-z","article-title":"Global trends in semen quality of young men: a systematic review and regression analysis","volume":"40","author":"Luo","year":"2023","journal-title":"J Assist Reprod Genet"},{"key":"2024051505515468600_ref2","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1111\/jmwh.12500","article-title":"Endocrine-disrupting chemicals and reproductive 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