Regulation of cAMP on the first mitotic cell cycle of mouse embryos

Abstract

Mitosis promoting factor (MPF) plays a central role during the first mitosis of mouse embryo. We demonstrated that MPF activity increased when one-cell stage mouse embryo initiated G2/M transition following the decrease of cyclic adenosine 3', 5'-monophosphate (cAMP) and cAMP-dependent protein kinase (PKA) activity. When cAMP and PKA activity increases again, MPF activity decreases and mouse embryo starts metaphase-anaphase transition. In the downstream of cAMP/PKA, there are some effectors such as polo-like kinase 1 (Plk1), Cdc25, Mos (mitogen-activated protein kinase kinase kinase), MEK (mitogen-activated protein kinase kinase), mitogen-activated protein kinase (MAPK), Wee1, anaphase-promoting complex (APC), and phosphoprotein phosphatase that are involved in the regulation of MPF activity. Here, we demonstrated that following activation of MPF, MAPK activity was steady, whereas Plk1 activity fluctuated during the first cell cycle. Plk1 activity was the highest at metaphase and decreased at metaphase-anaphase transition. Further, we established a mathematical model using Gepasi algorithm and the simulation was in agreement with the experimental data. Above all the evidences, we suggested that cAMP and PKA might be the upstream factors which were included in the regulation of the first cell cycle development of mouse embryo.

The methyltransferase Setdb1 is essential for meiosis and mitosis in mouse oocytes and early embryos

“…Some Setdb1 m−z+ embryos went through the first cleavage division, but these embryos displayed chromosome segregation defects. Given that the meiosis-to-mitosis transition is mechanistically a gradual process lasting over many cleavage divisions (Courtois et al, 2012;Cui et al, 2008;Poueymirou and Schultz, 1987;Yu et al, 2008), we propose that the observed defects in G2/M transition and mitosis underlie the arrest of Setdb1 m−z+ embryos at successive stages of preimplantation development.…”

“…Interactions between microtubules and kinetochores on chromosomes ensure proper chromosome segregation (Watanabe, 2012). Following fertilization, embryonic cleavage divisions share initially common mechanisms with meiosis such as a cAMP-PKA-dependent nuclear envelope breakdown (NEBD) and MTOC-driven bipolar spindle formation (Courtois et al, 2012;Cui et al, 2008;Poueymirou and Schultz, 1987;Yu et al, 2008). The organization of spindles gradually transitions over eight cleavage divisions from a large meiotic spindle into a short mitotic spindle harboring centrosomes (Courtois et al, 2012;Kubiak et al, 2008).…”

Characterization of p70 S6 kinase 1 in early development of mouse embryos

“…It is well-known that MPF is a critical regulator of early embryo development in mice (Yu et al, 2005(Yu et al, , 2008. This factor is composed of a catalytic subunit, Cdc2, with a histone H1 kinase activity and a regulatory subunit, cyclin B (King et al, Fig.…”

CFTR mediates bicarbonate-dependent activation of miR-125b in preimplantation embryo development

“…After its entry, HCO 3 − has been shown to activate the downstream cAMP-dependent pathway in a number of cell types via its sensor, the soluble adenylate cyclase (sAC) [33]. Interestingly, it has been shown that cAMP activation is essential for embryo development [34] and both CFTR and sAC are expressed in preimplantation embryos [5] (Supplementary information, Figures S1 and S2), suggesting their possible involvement in mediating HCO 3 − -dependent cAMP signaling in preimplantation embryo. Given the recently revealed role of miR-125b in embryo development of lower organisms, we proposed that the high HCO 3 − content present in the female reproductive tract may exert its effect on embryo development by regulating miR-125b expression via CFTR-mediated cAMP pathway.…”