Down-regulation of miR-378a-3p induces decidual cell apoptosis: a possible mechanism for early pregnancy loss.

STUDY QUESTION: Do microRNAs (miRNAs) contribute to human early pregnancy loss (EPL)?

SUMMARY ANSWER: miR-378a-3p expression is regulated by progesterone and is down-regulated in ducidua of EPL patients which may contribute to decidual apoptosis through Caspase-3 activation.

WHAT IS KNOWN ALREADY: A variety of miRNAs have been demonstrated to be associated with the development of decidualization and placental formation. However, little has been reported on the roles of miRNA in the pathogenesis of EPL.

STUDY DESIGN, SIZE, DURATION: Normal and EPL decidual tissues were collected from patients with normal pregnancies undergoing elective termination of gestation, and from patients with EPL, respectively.

PARTICIPANTS/MATERIALS, SETTING, METHODS: miRNA microarrays were used to identify the differentially expressed miRNAs between normal and EPL decidua, and miRNA expression was confirmed by qRT-PCR, qRT-PCR, western blotting and luciferase reporter assays were employed to validate the downstream targets of miR-378a-3p. The effects of miR-378a-3p were evaluated using miR-378a-3p-transfected decidual cells.

MAIN RESULTS AND THE ROLE OF CHANCE: Of note, 32 up-regulated miRNAs and 38 down-regulated miRNAs were identified by microarray analysis when comparing EPL to normal decidua. MiR-378a-3p was significantly down-regulated in the EPL decidua and was found to inversely regulate the expression of Caspase-3 by directly binding to its 3'-UTRs. In decidual cells, transfection of miR-378a-3p mimics resulted in the inhibition of cell apoptosis and in the increase of cell proliferation through Caspase-3 suppression. Moreover, we found that progesterone could induce the expression of miR-378a-3p in decidual cells.

LIMITATIONS, REASONS FOR CAUTION: This study focused on the function of miR-378a-3p and its target Caspase-3, however, numerous other targets and miRNAs may also be responsible for the pathogenesis of EPL. Therefore, further studies are required to elucidate the role of miRNAs in EPL.

WIDER IMPLICATIONS OF THE FINDINGS: Our findings indicate that miR-378a-3p may contribute to the development of EPL, and that it could serve as a new potential predictive and therapeutic target of progesterone-treatment for EPL.

STUDY FUNDING/COMPETING INTEREST: This study was supported by National Basic Research Program of China (No.2012CB944900); National Science Foundation of China (No.31471405 and 81490742, No.81361120246); The National Science and Technology Support Program (No.2012BA132B00). Authors declare no competing interests.