Exocannabinoids effect on in vitro bovine oocyte maturation via activation of AKT and ERK1/2

Abstract

Endocannabinoids are known to mediate practically all reproductive events in mammals; however, little is known about their role in oocyte maturation. Through RT-PCR and immunocytochemistry, this study confirms the presence of CB1 and CB2 cannabinoid receptors in bovine oocytes and shows how exposure to the exogenous cannabinoids HU-210 and THC during their in vitro maturation (IVM) activates the phosphorylation of AKT and ERK1/2 proteins associated with the resumption of meiosis. Although supplementation with HU-210 or THC during IVM did not increase blastocyst yields, the expression of interferon tau (IFNτ) and gap junction alpha-1 protein (GJA1) was enhanced at the blastocyst stage. Our data suggest that cannabinoid agonists may be useful IVM supplements as their presence during oocyte maturation upregulates the expression in blastocysts of key genes for embryo quality.

Implication of mu opioid receptor in the in vitro maturation of oocytes and its effects on subsequent fertilization and embryo development in mice

“…The Oprm1 transcript was present at GV stage and granulosa cells, whereas at MI and MII stages no signal was detected. This fact has been described previously for other transcripts (Agirregoitia et al, ; López‐Cardona et al, ) since mRNA is selective degraded during oocyte maturation and transcription becomes silent from the resumption of meiosis until two‐cell stage in mice (Gosden & Lee, ; Picton, Briggs, & Gosden, ). Mu opioid receptor transcript has also been detected in oocytes and granulosa cells from other species, such as bovine, equine, human, or porcine (Agirregoitia et al, ; Dang‐Nguyen et al, ; Dell'Aquila et al, ; Lunger et al, ).…”

“…Although there is no previous evidence of opioid action on AKT phosphorylation in oocytes, morphine is able to stimulate its phosphorylation in neuronal cells (Madishetti et al, ). Likewise, it has been described that the exposure to cannabinoids, very related to opioids due to their similar action mechanism, was able to accelerate the AKT activation both in granulosa cells and oocytes during maturation in bovine and mice (López‐Cardona et al, ).…”

UCH-L1 inhibitor LDN-57444 hampers mouse oocyte maturation by regulating oxidative stress and mitochondrial function and reducing ERK1/2 expression

“…ERK1/2, members of MAPK superfamily, have been found to be closely associated with oocyte maturation [ 42 , 43 ]. For example, a previous study pointed out that ERK1/2 expression was notably reduced in matured bovine oocytes compared with unmatured or control oocytes [ 44 ].…”

CB1cannabinoid receptor drives oocyte maturation and embryo development via PI3K/Akt and MAPK pathways

“…1B-E). In previous work, it was also detected the lack of Cnr1 mRNA but the presence of CB 1 protein on bovine oocytes (5). In fact, because during the resumption of oocyte meiosis the transcription of new RNAs falls to barely detectable levels and some RNAs are degraded, it is known that the timing and pattern of RNA synthesis in the oocyte may not necessary coincide with translation into an active protein (28).…”

“…Components of the endocannabinoid system have been identified in human (2)(3)(4)(5), and rat (6) follicles. The cannabinoid receptors 1 (CNR1, also called CB 1 ) and 2 (CNR2, also called CB 2 ) are GPCR-Gais that mainly inhibit adenylyl cyclase, reducing cyclic AMP and blocking PKA.…”