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Hence, in chickens, excessive ambient temperature negatively influences their reproductive performance and health. Heat stress induces inflammation and oxidative stress, thereby rendering many reproductive organs dysfunctional. In this study, we evaluated the effects of the supplementation of dietary quercetin and vitamin E on the uterine function, eggshell quality via estrogen concentration, calcium metabolism, and antioxidant status of the uterus of laying hens under heat stress. The ambient temperature transformation was set at 34 \u00b1 2 \u00b0C for 8 h\/d (9:00 am\u20135:00 pm), which was followed by 22 \u00b0C to 28 \u00b0C for 16 h\/d. Throughout the experiment, the relative humidity in the chicken\u2019s pen was at 50 to 65%. A total of 400 Tianfu breeder hens (120-days-old) were randomly divided into four dietary experimental groups, including basal diet (Control); basal diet + 0.4 g\/kg quercetin; basal diet + 0.2 g\/kg vitamin E; and basal diet + the combination of quercetin (0.4 g\/kg) and vitamin E (0.2 g\/kg). The results show that the combination of quercetin and vitamin E significantly increased the serum alkaline phosphatase levels and the antioxidant status of the uterus (p &lt; 0.05). In addition, the combination of quercetin and vitamin E significantly increased the concentrations of serum estrogen and progesterone, as well as elevated the expression of hypothalamic gonadotropin-releasing hormone-1 and follicular cytochrome P450 family 19 subfamily A member-1 (p &lt; 0.05). We also found that the calcium levels of the serum and uterus were significantly increased by the synergistic effects of quercetin and vitamin E (p &lt; 0.05), and they also increased the expression of Ca2+-ATPase and the mRNA expression of calcium-binding-related genes in the uterus (p &lt; 0.05). These results are consistent with the increased eggshell quality of the laying hens under heat stress. Further, the combination of quercetin and vitamin E significantly increased the uterine morphological characteristics, such as the height of the uterine mucosal fold and the length of the uterine mucosa villus of the heat-stressed laying hens. These results collectively improve the uterine function, serum and uterine calcium concentration, eggshell strength, and eggshell thickness (p &lt; 0.05) in heat-stressed laying hens. Taken together, we demonstrated in the present study that supplementing the combination of dietary quercetin and vitamin E alleviated the effects of heat stress and improved calcium metabolism, hormone synthesis, and uterine function in the heat-stressed laying hens. Thus, the supplementation of the combination of quercetin and vitamin E alleviates oxidative stress in the eggshell gland of heat-stressed laying hens, thereby promoting calcium concentration in the serum and eggshell gland, etc., in laying hens. Hence, the combination of quercetin and vitamin E promotes the reproductive performance of the laying hens under heat stress and can also be used as a potent anti-stressor in laying hens.<\/jats:p>","DOI":"10.3390\/ani14111554","type":"journal-article","created":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T08:30:22Z","timestamp":1716539422000},"page":"1554","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Supplementation of the Combination of Quercetin and Vitamin E Alleviates the Effects of Heat Stress on the Uterine Function and Hormone Synthesis in Laying Hens"],"prefix":"10.3390","volume":"14","author":[{"given":"Xueqing","family":"Cao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2682-1993","authenticated-orcid":false,"given":"Felix Kwame","family":"Amevor","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaxia","family":"Du","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youhao","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Wei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0610-9635","authenticated-orcid":false,"given":"Gang","family":"Shu","sequence":"additional","affiliation":[{"name":"Department of Basic Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Feng","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry and Veterinary Medicine, Tibet Academy of Agricultural and Animal Husbandry Science, Lhasa 851418, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0633-4701","authenticated-orcid":false,"given":"Xiaoling","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.3382\/ps.2011-01951","article-title":"Interaction of hen 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