METTL3 is essential for normal progesterone signaling during embryo implantation via mA-mediated translation control of progesterone receptor.

Embryo implantation, a crucial step in human reproduction, is tightly controlled by estrogen and progesterone (P) via estrogen receptor alpha and progesterone receptor (PGR), respectively. Here, we report that -methyladenosine (mA), the most abundant mRNA modification in eukaryotes, plays an essential role in embryo implantation through the maintenance of P signaling. Conditional deletion of methyltransferase-like 3 (), encoding the mA writer METTL3, in the female reproductive tract using a Cre mouse line with promoter () resulted in complete implantation failure due to pre-implantation embryo loss and defective uterine receptivity.