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Decidualization is a critical process for successful embryo implantation and subsequent placenta formation. The characterization and physiological function of lncRNA during decidualization remain largely unknown. In the present study, we conducted RNA-sequencing analysis to compare gene expression between decidua of days 6 and 8, and normal pregnant endometrium (day 4). A total of 2332 high-confidence putative lncRNA transcripts were expressed. Functional clustering analysis of  cis  and  trans  lncRNA targets showed that differentially expressed lncRNAs may regulate multiple gene ontology terms and pathways that have important functions in decidualization. Subsequent analyses using qRT-PCR validated that eight of all lncRNAs were differentially regulated in mice uteri during decidualization, both  in vivo  and  in vitro . Furthermore, we showed that differentially expressed lncRNA of  Hand2os1  was specifically detected in stromal cells on days 2 to 5 of pregnancy and was strongly upregulated in decidual cells on days 6–8 of pregnancy. Similarly,  Hand2os1  expression was also strongly expressed in decidualized cells following artificial decidualization, both  in vivo  and  in vitro . In uterine stromal cells, P 4  was able to significantly upregulate the expression of  Hand2os1 , but upregulation was impeded by RU486, whereas E 2  appeared to have no regulating effect on  Hand2os1  expression. Concurrently,  Hand2os1  significantly promoted the decidual process  in vitro  and dramatically increased decidualization markers  Prl8a2  and  Prl3c1 . Our results provide a valuable catalog for better understanding of the functional roles of lncRNAs in pregnant mouse uteri, as it relates to decidualization.

Progesterone-induced RNA Hand2os1 regulates decidualization in mice uteri