| First Author | Filis P | Year | 2013 |
| Journal | Mol Hum Reprod | Volume | 19 |
| Issue | 5 | Pages | 290-301 |
| PubMed ID | 23295235 | Mgi Jnum | J:317564 |
| Mgi Id | MGI:6855304 | Doi | 10.1093/molehr/gas067 |
| Citation | Filis P, et al. (2013) Implantation failure in mice with a disruption in Phospholipase C beta 1 gene: lack of embryonic attachment, aberrant steroid hormone signalling and defective endocannabinoid metabolism. Mol Hum Reprod 19(5):290-301 |
| abstractText | Phospholipase C beta 1 (PLCbeta1) is a downstream effector of G-protein-coupled receptor signalling and holds central roles in reproductive physiology. Mice with a disruption in the Plcbeta1 gene are infertile with pleiotropic reproductive defects, the major reproductive block in females being implantation failure. Here, PLCbeta1 was demonstrated at the luminal and glandular epithelia throughout the pre- and peri-implantation period, with transient stromal expression during 0.5-1.5 days post coitum (dpc). Examination of implantation sites at 4.5 dpc showed that in females lacking functional PLCbeta1 (knock-out (KO) females), embryos failed to establish proper contact with the uterine epithelium. Proliferating luminal epithelial cells were evident in KO implantation sites, indicating failure to establish a receptive uterus. Real-time PCR demonstrated that KO implantation sites had aberrant ovarian steroid signalling, with high levels of estrogen receptor alpha, lactoferrin and amphiregulin mRNA, while immunohistochemistry revealed very low levels of estrogen receptor alpha protein, possibly due to rapid receptor turnover. KO implantation sites expressed markedly less fatty acid amide hydrolase and monoacylglycerol lipase, indicating that endocannabinoid metabolism was also affected. Collectively, our results show that PLCbeta1 is essential for uterine preparation for implantation, and that defective PLCbeta1-mediated signalling during implantation is associated with aberrant ovarian steroid signalling and endocannabinoid metabolism. |
