title: Melatonin-related genes expressed in the mouse uterus during early gestation promote embryo implantation.
abstract: Melatonin, a superior antioxidant, is an important molecule which regulates female reproduction due to its receptor-mediated and receptor-independent antioxidant actions. In this study, we investigated the effect of melatonin on early gestation in a mouse model. During early gestation, the expression of the melatonin's rate-limiting enzyme, AANAT, gradually increased - in the uterus while the MT2 melatonin receptor was only expressed at day 2 of gestation and no MT1 was detected. Based on these findings, we conducted a melatonin injection experiment which demonstrated that 15 mg/kg melatonin significantly improved the number of implantation sites and the litter size. Also, the blastocyst and uterus were collected to identify the local action of melatonin. In the melatonin-treated mice, the endometrium was thicker than in the control mice; melatonin also caused an increase in density of uterine glands, and the uterine gland index (UGI) was significantly elevated over that of the control. Serum steroid hormone measurements revealed that at day 6 of gestation (postimplantation), melatonin significantly downregulated the E2 level, with no obvious effects on progesterone. Gene expression assay revealed that melatonin significantly upregulated expression of HB-EGF, a crucial gene involved in implantation as well as its receptor ErbB1 in the blastocyst. In addition, PRA, an important gene which influences the decidual response and luminal cell differentiation, p53, which regulates uterine through leukaemia inhibitory factor (LIF), were both increased after melatonin treatment. These data suggest that melatonin and its MT2 receptor influence early gestation. Exogenous melatonin treatment can improve mouse embryo implantation and litter size, which may have important applications in human reproductive health and animal husbandry.
authors.affiliation: National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, China.
authors.forename: Changjiu
authors.initials: C
authors.lastname: He
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.forename: Kuanfeng
authors.initials: K
authors.lastname: Zhu
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Xu
authors.forename: Yile
authors.initials: Y
authors.lastname: Song
authors.forename: Yukun
authors.initials: Y
authors.lastname: Song
authors.forename: Guoshi
authors.initials: G
authors.lastname: Liu
mesh_terms: D000818:Animals; D047068:Arylalkylamine N-Acetyltransferase / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D010064:Embryo Implantation / Q000235:genetics*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D008297:Male; D008550:Melatonin / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D044123:Receptor, Melatonin, MT2 / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D014599:Uterus / Q000737:chemistry / Q000378:metabolism*
chemical_list: D044123:Receptor, Melatonin, MT2; D047068:Arylalkylamine N-Acetyltransferase; D008550:Melatonin
keywords: AANAT; MT2; antioxidant; early pregnancy; embryo implantation; melatonin; uterus