Unique and independent role of the GABA(B1) subunit in embryo implantation and uterine decidualization in mice

Embryo implantation and decidualization are crucial for successful pregnancy, which include multiple genes and signaling pathways, while the precise mechanism regarding embryo implantation and decidualization has yet to be explored. The GABA which activates GABA(A) or GABA(B) receptors has been found playing an important role in early pregnancy. Here we seek to investigate whether GABA(B) receptors participate in embryo implantation in mice. This study first characterized the spatiotemporal expression pattern of GABA(B) receptors in the uterus during the peri-implantation period and found that GABA(B1) expression was drastically upregulated in stromal cells on days 4–6, a period of embryo implantation and early stages of decidualization. Embryo delayed implantation and oil-induced decidualization models were further used to confirm that the GABA(B1) was associated with embryo implantation and decidualization. We also found estrogen or progesterone had no directly effect on expression of GABA(B1) in ovariectomized model. Because we were unable to detect significant GABA(B2) which couples with GABA(B1) to form whole GABA(B) receptors, and the agonist and antagonist of whole GABA(B) receptors had weak effect on the proliferation and differentiation of stromal cells as well, we excluded the possibility whole GABA(B) receptors function, and concluded it should be non-classical signals of GABA(B1) involving in embryo implantation and decidualization. Future studies should focus on investigating the roles and mechanisms of GABA(B1) during embryo implantation and decidualization.