The beneficial effect of repaglinide on in vitro maturation and development ability of immature mouse oocytes

Abstract

Repaglinide is a hypoglycemic drug, causing depolarization of the cell membrane, opening the voltage-gated calcium channels, and then increasing intracellular calcium in the pancreatic B cells by inhibition of the K-ATP-sensitive channels. Oocyte in vitro maturation (IVM) is influenced by different factors such as calcium signaling. In this study, we examined the effects of repaglinide on in vitro maturation and fertilization ability of mouse oocyte. Immature oocytes were isolated from female Naval Medical Research Institute mice which are 6-8 wk old mechanically and then cultured in 30 μl droplets of T6 medium with different concentrations of repaglinide. The control group did not receive repaglinide (R). Treatment groups received different concentrations (5, 10, and 100 nM and 1 and 10 μM) of repaglinide (R, R, R, R, and R, respectively). Oocyte in vitro maturation rate was assessed after 24 h. In vitro fertilization was performed using metaphase II oocytes obtained from R and R treatments. Embryo cleavage rate was calculated at 48 h post-IVF. Chi-square test was used for evaluating difference between control and treatment groups (p < 0.05). Oocyte maturation rate after 24 h in treatment groups R, R, R, and R was significantly higher than that in the control (p < 0.05). Supplementation of medium with 1 μM of repaglinide (R) during IVM significantly improved outcome of embryo cleavage rate than control at 48 h post-IVF (p < 0.05). In conclusion, repaglinide can be considered as an effective agent for in vitro oocyte maturation and embryo cleavage.

In vitro maturation medium supplementation: utilization of repaglinide, L-carnitine, and mesenchymal stem cell-conditioned medium to improve developmental competence of oocytes derived from endometriosis mouse models

“…Thus, adding anti-oxidative components to the IVM medium of EMS subjects is likely to provide more appropriate conditions and boost maturation, fertilization, and further embryo development (29). We recently discovered that supplementing IVM medium with RG promotes oocyte maturation and embryo cleavage rate by elevating the intracellular calcium concentration (9). In line with this, the present findings revealed that RG significantly improved nuclear oocyte maturation in normal mice.…”

“…It belongs to the meglitinide class of short-acting insulin secretagogues, which induce insulin secretion by attaching to the b cells of the pancreas (8). RG achieves this by inhibition of the K-ATP-sensitive channels in the membrane of the b cells (9). This depolarizes the b cells, allowing voltage-gated calcium channels to open, and the subsequent calcium influx stimulates insulin release (10).…”

Effects of In Vitro Repaglinide Supplementation on Improving Sperm Motility Parameters, Viability, and DNA Integrity in Normozoospermic and Asthenozoospermic Men

“… Fernandes et al (2016) showed that both inhibition and activation of K-ATP channels with drugs targeting K-ATP channels such as glibenclamide, 2, 4-dinitrophenol (DNP), and pinacidil are useful in maintaining Ca 2+ homeostasis in oocytes in in vitro culture. Our research team recently indicated that the application of repaglinide in IVM, IVF, and follicle growth culture medium significantly improved in vitro mice oocyte maturation, fertilization, embryo cleavage, and follicle growth rates, probably by elevating intracellular calcium concentrations ( Kalehoei & Azadbakht, 2017 ; Awadh et al , 2019 ; 2020 ). The study of Mahdi & AL-Hady (2021) showed that combination treatments with metformin (500 mg/kg) and repaglinide (4 mg/kg) in diabetic rats had a positive effect on sperm parameters such as motility and viability.…”

“…An aliquot without repaglinide was used as a control and for the experimental groups the medium was supplemented with 100 nM or 1 µM concentrations of repaglinide. The two repaglinide concentrations were selected from a previous study by Kalehoei & Azadbakht (2017) . Dimethyl sulfoxide 0.1% (DMSO) was used to dissolve repaglinide as described by Fernandes et al (2016) .…”