Department of Biology, Faculty of Basic Sciences, Razi University, Kermanshah, Iran.
Department of Clinical Sciences, Faculty of Veterinary Medicine, Razi University, Kermanshah, Iran.
Braz J Med Biol Res. 2022 Apr 27;55:e11948. doi: 10.1590/1414-431X2022e11948. eCollection 2022.
Endometriosis (EMS) is one of the most prevalent causes for female infertility. Herein, we investigated the effect of the repaglinide (RG), L-carnitine (LC), and bone marrow mesenchymal stem cell-conditioned medium (BMSC-CM) supplementation during in vitro maturation (IVM) on the quality, maturation, and fertilization rates, as well as embryonic quality and development of oocytes derived from normal and EMS mouse model. Immature oocytes were collected from two groups of normal and EMS-induced female NMRI mice at 6-8 weeks of age. Oocytes were cultured in IVM medium unsupplemented (control group), or supplemented with 1 M RG, 0.3 and 0.6 mg/mL LC, and 25 and 50% BMSC-CM. After 24 h of oocyte incubation, IVM rate and antioxidant status were assessed. Subsequently, the rates of fertilization, cleavage, blastulation, and embryonic development were assessed. Our results demonstrated that supplementation of IVM medium with LC and BMSC-CM, especially 50% BMSC-CM, significantly enhanced IVM and fertilization rates, and markedly improved blastocyst development and total blastocyst cell numbers in EMS-induced mice compared to the control group (53.28±0.24 vs 18.09±0.10%). Additionally, LC and BMSC-CM were able to significantly modulate EMS-induced nitro-oxidative stress by boosting total antioxidant capacity (TAC) and mitigating nitric oxide (NO) levels. Collectively, LC and BMSC-CM supplementation improved oocyte quality and IVM rates, pre-implantation developmental competence of oocytes after in vitro fertilization, and enhanced total blastocyst cell numbers probably by attenuating nitro-oxidative stress and accelerating nuclear maturation of oocytes. These outcomes may provide novel approaches to refining the IVM conditions that can advance the efficiency of assisted reproductive technologies in infertile couples.
子宫内膜异位症 (EMS) 是女性不孕的最常见原因之一。在此，我们研究了在体外成熟 (IVM) 期间补充瑞格列奈 (RG)、左旋肉碱 (LC) 和骨髓间充质干细胞条件培养基 (BMSC-CM) 对来自正常和 EMS 小鼠模型的卵母细胞质量、成熟和受精率以及胚胎质量和发育的影响。将 6-8 周龄的正常和 EMS 诱导的 NMRI 雌性小鼠的未成熟卵母细胞分别收集在两组中。将卵母细胞在未补充 (对照组) 或补充 1M RG、0.3 和 0.6mg/mL LC 以及 25%和 50%BMSC-CM 的 IVM 培养基中培养 24 小时，评估 IVM 率和抗氧化状态。随后，评估受精、卵裂、囊胚形成和胚胎发育率。我们的结果表明，与对照组相比，LC 和 BMSC-CM 补充 IVM 培养基显著提高了 EMS 诱导的小鼠的 IVM 和受精率，并显著改善了囊胚发育和总囊胚细胞数（53.28±0.24 对 18.09±0.10%）。此外，LC 和 BMSC-CM 能够通过提高总抗氧化能力 (TAC) 和减轻一氧化氮 (NO) 水平来显著调节 EMS 诱导的硝基氧化应激。总的来说，LC 和 BMSC-CM 的补充通过减轻硝基氧化应激和加速卵母细胞核成熟，提高了卵母细胞的质量和 IVM 率、体外受精后卵母细胞的着床前发育能力，并增加了总囊胚细胞数。这些结果可能为改进 IVM 条件提供新方法，从而提高不孕夫妇辅助生殖技术的效率。
