Evaluation role of beta-2 adrenoceptor agonist and antagonist in the expression of gap junction genes (connexin 37/43) in cumulus cells of women with poor ovarian response

Connexon is a membrane structural protein in the gap junctions. These cellular connections are responsible for transporting ions and messenger molecules to the oocyte. This study aimed to investigate the role of beta-2-adrenoceptors in the process of follicle growth based on the expression of the two connexins 37/43 in the gap junctions that have a primary role in the mitotic resumption and oocyte maturation.

This case-control study was conducted from April 2019 to November 2020 at the Reproductive Health Research Center of Tehran Imam Khomeini Hospital was performed on women with the poor ovarian response (POR) and control (women donate eggs) groups. Both groups had entry criteria with a body mass index under 28 m2/kg and 20-45 years old. Exit criteria were including no drug use except ovarian stimulants and no illness. The diagnosis was made agreeing to the Bologna model criterion. Ovulation stimulation cycle was performed, and then after the puncture, cumulus cells were isolated by enzyme and were freezing in -80 centigrade until the time of inserting into the cell culture medium. Isoproterenol (agonist) and propranolol (antagonist) at a concentration of 100 nM were added to the culture medium as the beta-2 adrenoceptors selective drugs. After culture, RNA extraction was performed and the concentration was read by Nanodrop, and then cDNA was synthesized. Gene expression was determined by real-time PCR.

The findings of connexin expression in the three study groups: without the drug (P<0.001), propranolol (P<0.001), and isoproterenol (P<0.001) were significant compared to the control group. Isoproterenol decreased expression but propranolol increased it (P<0.001).

These findings confirm the important role of connexins 37 and 43 in cumulus cleft junctions that propranolol was able to increase its expression. Therefore, we suggest firstly these two connexins can be an effective target for oocyte growth and maturation. Secondly, propranolol could be a new treatment for women with POR and be effective in assisted reproductive technology (ART).