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

Abstract

Endocannabinoids have been recognized as mediators of practically all reproductive events in mammals. However, little is known about the role of this system in oocyte maturation. In a mouse model, we observed that activation of cannabinoid receptor 1 (CB) during oocyte maturation modulated the phosphorylation status of Akt and ERK1/2 and enhanced the subsequent embryo production. In the absence of CB, oocyte maturation was impaired and embryo development delayed. Cannabinoid receptor 2 (CB) was unable to rescue these effects. Finally, we confirmed abnormal oocyte maturation rather than impaired embryonic transport through the oviduct in CB knockouts. Our data suggest that cannabinoid agonists may be useful maturation supplements. For fertilization patients intolerant to gonadotropins, this could be a promising and only option.-López-Cardona, A. P., Pérez-Cerezales, S., Fernández-González, R., Laguna-Barraza, R., Pericuesta, E., Agirregoitia, N., Gutiérrez-Adán, A., Agirregoitia, E. CB cannabinoid receptor drives oocyte maturation and embryo development PI3K/Akt and MAPK pathways.

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, ).…”

“…Relative results to control group (0 nM) are shown and results are the means ± SEM of five independent experiments. The different combinations of letters indicate significant differences between groups; p < .05 in all cases 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, 2017, 2016.…”

The Expression of ERK1/2 in Female Yak (Bos grunniens) Reproductive Organs

“…Meanwhile, a suitable biochemical component of the oviduct content provides an adapt circumstance for the development of the preimplantation embryo. On the contrary, the incorrect function of the oviduct may be the result in infertility, or deficiency of the embryonal development [59,60]. The oviduct content, also named as oviduct fluid, consists of proteins secreted by the secretory cells of the oviduct epithelium and other plasma-derived constituents [61,62].…”

Construction of Gene Network in Type 2 Diabetes with Genome-Wide Association Study

“…The phosphatidylinositol 3-kinase (phosphoinositide, 3-kinase, PI3K) [8]as an example, in the KEGG database, the PI3K gene is involved in 60 biological pathways, including PI3K-Akt [9] signaling pathway, Jak-STAT signaling pathway, TNF signaling pathway, insulin signaling pathway and type 2 diabetes [10], in a variety of metabolic processes were related to the expression of PI3K has correlation PI3K signaling pathway and glucose production, insulin secretion and signal transduction of literature reports, in the liver, PI3K signaling pathway mediated by glucose, PI3K signaling pathway is related to insulin sensitivity. Through the above process is often selected genes in various biological processes must be able to participate in the molecular biological pathway most, through the intermediate gene mediated to susceptibility genes connected.…”