Effects of cilostamide and forskolin on the meiotic resumption and embryonic development of immature human oocytes

Abstract

Combined treatment of cilostamide and forskolin positively influences oocyte developmental competence by exhibiting a synergistic effect on the prevention of GJC loss and resumption of meiosis.

Regulation of sheep oocyte maturation using cAMP modulators

“…Furthermore, meiotic resumption occurs in a rapid and uncontrolled manner [25]. However, the SPOM and related IVM models using elevated cAMP concentrations attenuated spontaneous meiosis, thereby resulting in a more gradual cessation of oocyte transcription and transition into the M-phase and promoting and prolonging oocyte-cumulus cell gap junction communication (GJC) [13,[32][33][34][35]. Part of the rationale for these approaches were substantial increases in cAMP occurred in vivo following LH-induction of the ovulatory cascade in porcine [36] and murine COCs [13,37].…”

Oocyte maturation and quality: role of cyclic nucleotides

“…Use of dbcAMP has proved highly successful and is now widely used in porcine IVM embryo production systems (Table 2). Other cAMP-elevating agents of note used for this approach include invasive adenylate cyclase (iAC; (Aktas et al 1995, Luciano et al 1999) and forskolin (Ali & Sirard 2005, Shu et al 2008. Forskolin, in particular, leads to rapid and large increases in whole COC and intra-oocyte cAMP (Thomas et al 2002, Bernal-Ulloa et al 2016 to levels that approximate the spike in COC cAMP levels that occur in vivo in response to LH (Fig.…”

“…A PDE inhibitor such as cilostamide can be included in the IVM phase, as used in SPOM version 1 (Albuz et al 2010) or omitted as per SPOM version 2 (Zeng et al 2013, Richani et al 2014b, Zeng et al 2014, Li et al 2016, and in the iAC and dbcAMP approaches (Funahashi et al 1997, Luciano et al 1999, Guixue et al 2001. It is noteworthy that in all induced IVM (high cAMP) approaches, oocyte meiotic maturation is induced as a result of the elevated CC cAMP, even in the presence of a PDE inhibitor (Dekel et al 1988, Shu et al 2008) (this does not or is less likely to occur in biphasic IVM). This may seem paradoxical, as pharmacological stimulation of cAMP synthesis in CCs increases intra-oocyte cAMP by at least an order of magnitude (Thomas et al 2002), initially preventing GVBD.…”

“…It is interesting that in induced IVM systems, GVBD occurs at a higher intra-oocyte cAMP concentration than in standard IVM (Wang et al 2011). Despite the improvements across species in oocyte developmental competence using induced IVM systems (Table 2), this mode of oocyte maturation does not typically improve MII rates, which would be useful in species such as human where IVM MII rates are typically low (~50%) (Shu et al 2008, Zeng et al 2013.…”

Reversible meiotic arrest in feline oocytes

“…Another important variable is the presence or absence of gonadotrophins and growth factors (eCG and EGF in our system) during the period of meiotic arrest. Some protocols require moving the COCs from a medium containing the meiosis arresting agent(s) to a fresh medium without these chemicals at a specific time of culture (Funahashi et al 1997;Somfai et al 2003;Kawashima et al 2008;Shu et al 2008). Other protocols expose COCs to meiosis-arresting agents at the same time as gonadotrophins or growth factors and maturation proceeds as the stimulatory signal of the gonadotrophins and growth factors overcomes the inhibitory cAMP signal (Downs et al 1988;Thomas et al 2004b;Albuz et al 2010).…”