Department of Digital Oncomorphology, National Medical Research Centre of Radiology, 2nd Botkinsky Pass., 3, 125284 Moscow, Russia.
Laboratory of Histology and Immunohistochemistry, Institute of Translational Medicine and Biotechnology, Sechenov University, Trubetskaya St., 8/2, 119991 Moscow, Russia.
Int J Mol Sci. 2024 Sep 20;25(18):10115. doi: 10.3390/ijms251810115.
Radiotherapy is one of the risk factors for radiation-induced premature ovarian failure and infertility in cancer patients. The development of methods for ovarian radioprotection remains relevant. Moreover, electrons are a little-studied and promising method of radiation with the least toxic effect on normal tissues. The assessment of intracellular mechanisms regulating the protective effects of leukocyte-poor platelet-rich plasma in a model of radiation-induced premature ovarian failure caused by electron irradiation. Wistar rats were divided into four groups, namely a control group, irradiation group (electron exposure), irradiation + leukocyte-poor platelet-rich plasma group, and only leukocyte-poor platelet-rich plasma group. Fragments of ovaries were removed and hormonal, oxidant, histological, and morphometric studies were carried out. The cell cycle of ovarian follicles and the inflammatory and vascular response were assessed using immunohistochemistry. The activity of MAPK, ERK, and PI3K pathways was also assessed using the RT-qPCR. We found that electron irradiation causes a decrease in the functional activity of the ovaries and the death of follicular cells through apoptosis. The administration of LP-PRP led to a partial restoration of the cytokine balance. In addition, minor ovarian damage and mild inflammation were observed in this group. Leukocyte-poor platelet-rich plasma components have anti-inflammatory, angiogenetic, and radioprotective effects, reducing the activation of the NOX4, caspase and cytokine cascades, and inflammatory response severity through the MAPK/p38/JNK signaling pathway. This leads to the induction of endogenous antioxidant protection, the repair of post-radiation follicular damage, and slowing down the development of radiation-induced premature ovarian failure after electron irradiation.
放射治疗是癌症患者发生辐射诱导性卵巢早衰和不孕的危险因素之一。开发卵巢放射防护方法仍然具有重要意义。此外，电子射线是一种研究较少但很有前途的辐射方法，对正常组织的毒性最小。本研究旨在评估白细胞减少富血小板血浆在电子照射诱导的卵巢早衰模型中调节其保护作用的细胞内机制。将 Wistar 大鼠分为对照组、照射组（电子暴露）、照射+白细胞减少富血小板血浆组和仅白细胞减少富血小板血浆组。切除卵巢片段，进行激素、氧化应激、组织学和形态计量学研究。使用免疫组织化学评估卵巢卵泡的细胞周期和炎症及血管反应。还使用 RT-qPCR 评估 MAPK、ERK 和 PI3K 通路的活性。我们发现，电子照射通过细胞凋亡导致卵巢功能活性下降和卵泡细胞死亡。LP-PRP 的给药导致细胞因子平衡部分恢复。此外，在该组中还观察到卵巢损伤较小和炎症较轻。白细胞减少富血小板血浆成分具有抗炎、血管生成和放射防护作用，通过 MAPK/p38/JNK 信号通路降低 NOX4、半胱天冬酶和细胞因子级联的激活以及炎症反应的严重程度。这导致内源性抗氧化保护的诱导、辐射后卵泡损伤的修复以及电子照射后卵巢早衰的发展减缓。
