{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T22:39:35Z","timestamp":1785191975743,"version":"3.55.0"},"reference-count":74,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,12]],"date-time":"2023-04-12T00:00:00Z","timestamp":1681257600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of the People\u2019s Republic of China","award":["31830091"],"award-info":[{"award-number":["31830091"]}]},{"name":"National Natural Science Foundation of the People\u2019s Republic of China","award":["32172733"],"award-info":[{"award-number":["32172733"]}]},{"name":"National Natural Science Foundation of the People\u2019s Republic of China","award":["BAIC05-2022"],"award-info":[{"award-number":["BAIC05-2022"]}]},{"name":"Beijing Innovation Consortium of Livestock Research System","award":["31830091"],"award-info":[{"award-number":["31830091"]}]},{"name":"Beijing Innovation Consortium of Livestock Research System","award":["32172733"],"award-info":[{"award-number":["32172733"]}]},{"name":"Beijing Innovation Consortium of Livestock Research System","award":["BAIC05-2022"],"award-info":[{"award-number":["BAIC05-2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In the current study, using Aanat and Mt2 KO mice, we observed that the preservation of the melatonergic system is essential for successful early pregnancy in mice. We identified that aralkylamine N-acetyltransferase (AANAT), melatonin receptor 1A (MT1), and melatonin receptor 1B (MT2) were all expressed in the uterus. Due to the relatively weak expression of MT1 compared to AANAT and MT2, this study focused on AANAT and MT2. Aanat and Mt2 KO significantly reduced the early implantation sites and the abnormal morphology of the endometrium of the uterus. Mechanistical analysis indicated that the melatonergic system is the key player in the induction of the normal nidatory estrogen (E2) response for endometrial receptivity and functions by activating the STAT signaling pathway. Its deficiency impaired the interactions between the endometrium, the placenta, and the embryo. The reduction in melatonin production caused by Aanat KO and the impairment of signal transduction caused by Mt2 KO reduced the uterine MMP-2 and MMP-9 activity, resulting in a hyperproliferative endometrial epithelium. In addition, melatonergic system deficiency also increased the local immunoinflammatory reaction with elevated local proinflammatory cytokines leading to early abortion in the Mt2 KO mice compared to the WT mice. We believe that the novel data obtained from the mice might apply to other animals including humans. Further investigation into the interaction between the melatonergic system and reproductive effects in different species would be worthwhile.<\/jats:p>","DOI":"10.3390\/ijms24087127","type":"journal-article","created":{"date-parts":[[2023,4,12]],"date-time":"2023-04-12T04:51:01Z","timestamp":1681275061000},"page":"7127","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The Uterine Melatonergic Systems of AANAT and Melatonin Membrane Receptor 2 (MT2) Are Essential for Endometrial Receptivity and Early Implantation in Mice"],"prefix":"10.3390","volume":"24","author":[{"given":"Xiao","family":"Ma","sequence":"first","affiliation":[{"name":"National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agricultural, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Scienceand Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agricultural, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Scienceand Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Likai","family":"Wang","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agricultural, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Scienceand Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laiqing","family":"Yan","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agricultural, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Scienceand Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunjie","family":"Liu","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agricultural, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Scienceand Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenkui","family":"Ma","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agricultural, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Scienceand Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengyun","family":"Ji","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agricultural, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Scienceand Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agricultural, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Scienceand Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5688-3645","authenticated-orcid":false,"given":"Guoshi","family":"Liu","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agricultural, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Scienceand Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/nrg1808","article-title":"Roadmap to embryo implantation: Clues from mouse models","volume":"7","author":"Wang","year":"2006","journal-title":"Nat. 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