The placental circulation is crucial for the development of mammalian embryos [1]. The labyrinth layer in the placenta is created by extensive villous branching of the trophoblast and vascularization arising from the embryonic mesoderm. In the labyrinth, materials are exchanged between the maternal and embryonic circulation. Recently, we have found that inositol 1,4,5-trisphosphate (IP₃) receptors (IP₃Rs) may be required for the placental vascularization.

IP₃Rs are intracellular Ca²⁺ release channels that have three subtypes in mammals (IP₃R1, IP₃R2 and IP₃R3) [2]. We previously showed that IP₃R1 and IP₃R2 played an essential role in heart development from the analysis of mouse embryo double knockout for IP₃R1 and IP₃R2 [3]. A previous report on the requirement for phospholipase (PLC) δ1 and δ3 [4] that produce IP₃ for placentation led us to investigate the placental defects by deletion of any subtypes of IP₃Rs. Our preliminary result revealed that embryonic vasculature in the labyrinth was impaired in the placenta double knockout for IP₃R1 and IP₃R3 at E9.25 (Fig. 32.1). The detailed phenotype and the underlying mechanism how the intracellular Ca²⁺ signaling via IP₃Rs may be implicated in the development of extraembryonic vasculature are under investigation.

Fig. 32.1

Cross sections of E9.25 placentas from the IP₃R1^+/−3^−/− (a and b) and IP₃R1^−/−3^−/− (c and d) mice. (b) and (d) show higher-power fields of the rectangular areas of the labyrinth in (a) and (c), respectively. (more...)

This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan (to K.U. and H.Y.).