As you pointed out, we infer that downregulation of PGRMC1 may be necessary for decidualization to proceed. To clarify this point, we further attempted to overexpress PGRMC1 by introducing expression vectors into primary ESCs under various conditions using lipofection and calcium phosphate transfection methods, as you suggested. Unfortunately, for reasons unknown, we were unable to establish ESCs overexpressing PGRMC1. In the present study, we found that not only knockdown of PGRMC1 but also functional inhibition with inhibitors promotes ESC decidualization in vitro. Furthermore, in a previous report, overexpression of PGRMC1 suppressed ESCs differentiation (Ref. 19). These results indicate that decreased PGRMC1 in the endometrium may be associated with accelerated dedifferentiation. As you suggested, we have changed the title significantly because further evidence was not available. We plan to establish a model of miR-resistant PGRMC1 overexpression using several ESCs cell lines to investigate the role of PGRMC1 in decidualization, and if possible, we would be happy to make this our next research topic.
The authors could consider whether an inducible miRNA-resistant PGRMC1 promoter could be designed.