Phospholipase C-beta1 signaling affects reproductive behavior, ovulation, and implantation

Infertility can result from a wide range of defects, from behavioral, through germ cell development and maturation, to fertilization or embryo development. Many of the hormones regulating these processes signal via G protein-coupled receptors, which in turn activate a range of plasma membrane enzymes including phospholipase C (PLC)-beta isoforms. Transgenic mice lacking functional Plc-beta1 (Plc-beta1 KO mice) have been noted to have severely impaired fertility, but there has been little study of the reproductive processes affected by lack of this enzyme. This study examined reproductive behavior, gonadal development, fertilization, and implantation in Plc-beta1 KO mice. Male and female Plc-beta1 KO mice exhibited impaired reproductive behavior. No other defect in reproduction was noted in males, raising the possibility that the reduced fertility of Plc-beta1 KO males could be due solely to impaired behavior. In contrast, female Plc-beta1 KO mice exhibited both behavioral and nonbehavioral defects. Plc-beta1 KO females ovulated only in response to exogenous hormones, with a large proportion of in vivo embryos recovered on embryonic d 4.5 exhibiting abnormal morphology. In addition, uteri of pregnant Plc-beta1 KO females exhibited an implantation defect, with poor embryo attachment and a failure to up-regulate cyclooxygenase-2 mRNA.