miR-144 and targets, c-fos and cyclooxygenase-2 (COX2), modulate synthesis of PGE2 in the amnion during pregnancy and labor.
Labor is initiated as a result of hormonal changes that are induced by the activation of the inflammatory response and a series of biochemical events. The amnion, which is the primary source of prostaglandin E2 (PGE2), plays an important role in the process of labor. In the present study, we uncovered a pathway in which c-fos, cyclooxygenase-2 (COX2) and miR-144 function as hormonal modulators in the amnions of pregnant mice and humans. miR-144 down-regulated the synthesis of PGE2 during pregnancy by directly and indirectly inhibiting COX2 expression and by directly inhibiting the expression of c-fos, a transcriptional activator of COX2 and miR-144. Estrogen (E2) activated c-fos, thus promoting the expression of miR-144 and COX2 during labor. However, the increase in COX2 resulted in the partial inhibition of COX2 expression by miR-144, thereby slightly reducing the secretion of PGE2. These observations suggest that miR-144 inhibits PGE2 secretion by section to prevent the initiation of premature labor. Up-regulated expression of miR-144, c-fos and COX2 was also observed both in preterm mice and in mice undergoing normal labor. In summary, miR-144, c-fos and COX2 play important roles in regulating PGE2 secretion in the amnion during pregnancy and labor.
Key Laboratory of Swine Genetics and Breeding of Agricultural Ministry and Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, People's Republic of China.
Huanan
H
Li
Key Laboratory of Swine Genetics and Breeding of Agricultural Ministry and Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, People's Republic of China.
Jiawei
J
Zhou
Key Laboratory of Swine Genetics and Breeding of Agricultural Ministry and Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, People's Republic of China.
Xiajie
X
Wei
Key Laboratory of Swine Genetics and Breeding of Agricultural Ministry and Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, People's Republic of China.
Ran
R
Chen
Key Laboratory of Swine Genetics and Breeding of Agricultural Ministry and Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, People's Republic of China.
Junnan
J
Geng
Key Laboratory of Swine Genetics and Breeding of Agricultural Ministry and Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, People's Republic of China.
Rong
R
Zheng
Key Laboratory of Swine Genetics and Breeding of Agricultural Ministry and Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, People's Republic of China.
Jin
J
Chai
Key Laboratory of Swine Genetics and Breeding of Agricultural Ministry and Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, People's Republic of China.
Fenge
F
Li
Key Laboratory of Swine Genetics and Breeding of Agricultural Ministry and Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, People's Republic of China.|The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China People's Republic of China.
Siwen
S
Jiang
D000818:Animals; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D035683:MicroRNAs / Q000235:genetics*; D007752:Obstetric Labor, Premature / Q000235:genetics* / Q000276:immunology; D011247:Pregnancy / Q000276:immunology*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*
D004967:Estrogens; D008070:Lipopolysaccharides; C554293:MIRN144 microRNA, human; C551064:MIRN144 microRNA, mouse; D035683:MicroRNAs; D016760:Proto-Oncogene Proteins c-fos; D051546:Cyclooxygenase 2; D015232:Dinoprostone