Department of Obstetrics and Gynecology, Adana City Training and Research Hospital, 01370 Adana, Turkey; Department of Histology and Embryology, Medicine Faculty, Zonguldak Bulent Ecevit University, 67600 Zonguldak, Turkey.
IVF Unit, Adana City Training and Research Hospital, 01370 Adana, Turkey; Department of Histology and Embryology, Medicine Faculty, Zonguldak Bulent Ecevit University, 67600 Zonguldak, Turkey.
Eur J Obstet Gynecol Reprod Biol. 2023 Sep;288:191-197. doi: 10.1016/j.ejogrb.2023.08.001. Epub 2023 Aug 6.
Premature ovarian failure (POF) is defined as the cessation of menstrual periods for at least 4-6 months before the age of 40 years, accompanied by FSH values measuring over 40 IU/L for a month. Radiation therapy, one of the cancer treatment methods, is known to accelerate ovarian aging by reducing and eliminating the number of primordial follicles in the ovarian follicle pool. Ionizing radiation has been reported to cause POF. The objective of this study is to investigate the impact of mesenchymal stem cell conditioned medium (hAMSCs-CM), which is isolated from the amniotic membrane of human placenta, on premature ovarian failure (POF) caused by whole-body irradiation. The study will focus on the ER stress and apoptosis mechanisms in the process.
A POF model was created by exposing rats to 7 Gy of whole-body irradiation. Serum-free hAMSCs-CM were then administered via the tail vein. Follicle count was performed on the ovaries, and immunohistochemistry was used to determine the expressions of GRP78, CHOP, IRE-1, caspase-12, caspase-9, caspase-3. TUNEL was also carried out, and levels of serum FSH, LH, E2, AMH, and oxidative stress marker 8-OHdG were measured.
The application of hAMSCs-CM has been found to have a positive impact on follicles affected by radiation. After treatment, the number of primordial, primary, secondary, and graafian follicles, which had previously decreased due to radiation, showed an increase. Furthermore, the number of atretic follicles, which had been increasing due to radiation, showed a decrease. ER is one of the targets affected by ionizing radiation. After ionizing radiation, the expressions of ER stress-related markers and apoptosis markers increased in the ovary. After hAMSCs-CM administration, the expressions of these markers and number of TUNEL-positive cells decreased. Following irradiation, anti-mullerian hormone (AMH) and estradiol (E2) levels decreased, while follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels increased. After administration of hAMSCs-CM, AMH and E2 levels increased, while FSH and LH levels decreased. Amnion membrane-derived mesenchymal stem cell conditioned medium can play a therapeutic role in ionizing radiation-induced premature ovarian failure by reducing endoplasmic reticulum stress and apoptosis.
卵巢早衰（POF）定义为 40 岁之前闭经至少 4-6 个月，同时 FSH 值持续 1 个月超过 40IU/L。放射治疗是癌症治疗方法之一，已知通过减少和消除卵巢卵泡池中原始卵泡的数量来加速卵巢衰老。有报道称电离辐射会导致 POF。本研究旨在探讨从人胎盘羊膜分离的间充质干细胞条件培养基（hAMSCs-CM）对全身照射引起的卵巢早衰（POF）的影响。该研究将重点关注内质网应激和细胞凋亡机制。
通过对大鼠进行 7Gy 全身照射创建 POF 模型，然后通过尾静脉给予无血清 hAMSCs-CM。对卵巢进行卵泡计数，并通过免疫组织化学测定 GRP78、CHOP、IRE-1、caspase-12、caspase-9、caspase-3 的表达。还进行了 TUNEL 检测，并测量血清 FSH、LH、E2、AMH 和氧化应激标志物 8-OHdG 的水平。
应用 hAMSCs-CM 对受辐射影响的卵泡产生了积极影响。治疗后，由于辐射而减少的原始、初级、次级和格拉夫卵泡的数量增加，而由于辐射而增加的闭锁卵泡数量减少。内质网是电离辐射作用的靶点之一。电离辐射后，卵巢中 ER 应激相关标志物和细胞凋亡标志物的表达增加。给予 hAMSCs-CM 后，这些标志物的表达和 TUNEL 阳性细胞的数量减少。照射后，抗苗勒管激素（AMH）和雌二醇（E2）水平下降，而卵泡刺激素（FSH）和黄体生成素（LH）水平升高。给予 hAMSCs-CM 后，AMH 和 E2 水平升高，而 FSH 和 LH 水平降低。羊膜来源的间充质干细胞条件培养基可通过减少内质网应激和细胞凋亡在电离辐射诱导的卵巢早衰中发挥治疗作用。
