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

• Published in: Molecular reproduction and development 2019-09, Vol.86 (9), p.1236-1244
• Main Authors: Olabarrieta, Estibaliz, Totorikaguena, Lide, Agirregoitia, Naiara, Agirregoitia, Ekaitz
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Cell culture; embryo; Fertilization; Granulosa cells; Immunocytochemistry; in vitro fertilization; in vitro maturation; Localization; MAP kinase; Maturation; Morphine; Naloxone; Narcotics; oocyte; Oocytes; Opioid receptors (type mu); opioids; Peptides; Polymerase chain reaction; Therapeutic applications
• ISSN: 1040-452X; 1098-2795
• DOI: 10.1002/mrd.23248

Oocyte maturation is the process by which immature oocytes acquire all the necessary characteristics for successful fertilization. The endogenous opioid peptides have been suggested to have a role modulating this process. However, little is known about its implication and the effect of exposing oocyte maturation to opioids on the subsequent fertilization and embryo development. Hence, in the present work, we focused on elucidating the function of the mu opioid receptor (OPRM1) in the modulation of the oocyte maturation. We analyzed the expression and localization of OPRM1 in mice oocytes and granulosa cells by reverse‐transcription polymerase chain reaction (RT‐PCR) and immunocytochemistry. To observe the activity of the OPRM1, immature oocytes were incubated with morphine agonist and/or naloxone antagonist and we evaluated the PI3K/Akt and MAPK pathways, as well as the effect on the subsequent fertilization and embryo development. OPRM1 was present in mice oocytes and granulosa cells, changing its expression pattern depending on the maturation stage. Moreover, morphine, modulating PI3K/Akt and MAPK pathways, helped oocytes to reach blastocyst stage, which was reverted by naloxone. These results propose the OPRM1 as a possible therapeutic target for in vitro maturation culture medium, as it could improve the blastocyst rates obtained in the actual reproduction assisted techniques. This manuscript provides information concerning the presence and function of the mu opioid receptor during oocyte in vitro maturation. The mu opioid receptor was present in mice oocytes and granulosa cells, changing its expression pattern depending on the maturation stage. Moreover, our research team showed, for the first time, that morphine, modulating PI3K/Akt and MAPK pathways, helped oocytes to reach blastocyst stage, which was blocked by naloxone. These results propose the mu opioid receptor as a possible therapeutic target for in vitro maturation culture medium, as it could improve the blastocyst rates obtained in the actual reproduction assisted techniques