Sumapraja Kanadi, Hestiantoro Andon, Liem Isabella Kurnia, Boediono Arief, Z Jacoeb Teuku
Division of Reproductive Immunoendocrinology, Department of Obstetrics and Gynecology, Faculty of Medicine Universitas Indonesia, Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia.
Cluster of Human Reproduction, Fertility and Family Planning, the Indonesian Medical Education and Research Institute Universitas Indonesia, Jakarta, Indonesia.
Int J Reprod Biomed. 2022 Jan 12;19(12):1037-1044. doi: 10.18502/ijrm.v19i12.10054. eCollection 2021 Dec.
The umbilical cord-derived mesenchymal stem cells conditioned medium (UC-MSCs-CM) produces secretomes with anti-apoptotic properties, and has the potential to prevent apoptosis of granulosa cells (GC) during controlled ovarian hyperstimulation.
To observe the effect of UC-MSCs-CM on the interaction between pro- and anti-apoptotic proteins and the influence of growth differentiation factor 9 (GDF9) production in GC.
UC-MSCs-CM was collected from umbilical cord stem cell culture on passage 4. GC from 23 women who underwent in vitro fertilization were cultured and exposed to UC-MSCs-CM for 24 hr. Then RNA of the GC was extracted and the mRNA expression of BCL-2 associated X (BAX), survivin and GDF9 were analysed using quantitative real-time PCR. The spent culture media of the GC were collected for measurement of insulin growth factor 1 using ELISA.
The expression of BAX was significantly different after UC-MSCs-CM exposure (4.09E-7 vs. 3.74E-7, p = 0.02). No significant changes occurred in survivin, BAX/survivin ratio, and GDF9 expression after UC-MSCs-CM exposure (p 0.05). The IGF-1 level of the CM was significantly higher after the CM was used as a culture medium for GC (2.28 vs. 3.07 1.72, p 0.001). A significant positive correlation was found between survivin and GDF9 (r = 0.966, p 0.001).
IGF-1 produced by UC-MSCs-CM can work in paracrine fashion through the IGF receptor, which can inhibit BAX and maintain GDF9 production. Moreover, under the influence of UC-MSCs-CM, GC are also capable of producing IGF-1, which can impact GC through autocrine processes.
脐带间充质干细胞条件培养基（UC-MSCs-CM）可产生具有抗凋亡特性的分泌组，有潜力在控制性卵巢过度刺激过程中防止颗粒细胞（GC）凋亡。
观察UC-MSCs-CM对促凋亡蛋白与抗凋亡蛋白相互作用的影响以及对GC中生长分化因子9（GDF9）产生的影响。
从第4代脐带干细胞培养物中收集UC-MSCs-CM。培养来自23例行体外受精妇女的GC，并使其暴露于UC-MSCs-CM中24小时。然后提取GC的RNA，使用定量实时PCR分析BCL-2相关X蛋白（BAX）、生存素和GDF9的mRNA表达。收集GC的用过的培养基，用酶联免疫吸附测定法测量胰岛素生长因子1。
暴露于UC-MSCs-CM后，BAX的表达有显著差异（4.09E-7对3.74E-7，p = 0.02）。暴露于UC-MSCs-CM后，生存素、BAX/生存素比值和GDF9表达无显著变化（p>0.05）。当CM用作GC的培养基后，CM中的IGF-1水平显著更高（2.28对3.07±1.72，p<0.001）。发现生存素与GDF9之间存在显著正相关（r = 0.966，p<0.001）。
UC-MSCs-CM产生的IGF-1可通过IGF受体以旁分泌方式发挥作用，抑制BAX并维持GDF9的产生。此外，在UC-MSCs-CM的影响下，GC也能够产生IGF-1，其可通过自分泌过程影响GC。
