Kim Se Jeong, Kim Tae Eun, Jee Byung Chul
Department of Obstetrics and Gynecology, Fertility Center of CHA Ilsan Medical Center, CHA University School of Medicine, Seoul, Republic of Korea.
Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea.
Clin Exp Reprod Med. 2022 Jun;49(2):93-100. doi: 10.5653/cerm.2022.05218. Epub 2022 May 30.
The impact of imatinib, a tyrosine kinase inhibitor, on ovarian follicles and several proteins related to follicular function and apoptosis was investigated in mice.
Saline, cyclophosphamide (Cp; 50 or 75 mg/kg), or imatinib (7.5 or 15 mg/kg) was injected once intraperitoneally into female B6D2F1 mice (18 mice in each group). In multiple ovarian sections, the number of various types of follicles and the proportion of good-quality (G1) follicles were counted. The levels of six proteins (anti-Müllerian hormone [AMH], BCL-xL, BAX, acid sphingomyelinase [A-SMase], caspase-3, and α-smooth muscle actin [α-SMA]) within the whole ovaries were quantified using Western blots.
Compared to the saline group, a significant reduction of the primordial follicle count was observed in the group treated with imatinib 7.5 and 15 mg/kg, as well as in the group treated with Cp 75 mg/kg. Administration of Cp significantly decreased the proportion of G1 primordial follicles, but administration of imatinib did not. No differences in the AMH, anti-apoptotic BCLX-L, pro-apoptotic BAX, and A-SMase levels in the ovarian tissues were observed among the five groups. However, caspase-3 and α-SMA levels were significantly higher in the imatinib and Cp groups than in the saline group.
The administration of imatinib to mice significantly reduced the primordial follicle count and increased the protein levels of caspase-3 and α-SMA. Our findings suggest that imatinib potentially exerts ovarian toxicity via apoptotic processes, similarly to Cp.
在小鼠中研究酪氨酸激酶抑制剂伊马替尼对卵巢卵泡以及几种与卵泡功能和凋亡相关蛋白质的影响。
将生理盐水、环磷酰胺（Cp；50或75mg/kg）或伊马替尼（7.5或15mg/kg）一次性腹腔注射到雌性B6D2F1小鼠体内（每组18只小鼠）。在多个卵巢切片中，计数各种类型卵泡的数量以及优质（G1）卵泡的比例。使用蛋白质免疫印迹法对整个卵巢内六种蛋白质（抗苗勒管激素[AMH]、BCL-xL、BAX、酸性鞘磷脂酶[A-SMase]、半胱天冬酶-3和α-平滑肌肌动蛋白[α-SMA]）的水平进行定量。
与生理盐水组相比，在接受7.5和15mg/kg伊马替尼治疗的组以及接受75mg/kg Cp治疗的组中，原始卵泡计数显著减少。给予Cp显著降低了G1原始卵泡的比例，但给予伊马替尼则没有。五组之间在卵巢组织中的AMH、抗凋亡BCLX-L、促凋亡BAX和A-SMase水平上未观察到差异。然而，伊马替尼组和Cp组中的半胱天冬酶-3和α-SMA水平显著高于生理盐水组。
给小鼠施用伊马替尼显著减少了原始卵泡计数，并增加了半胱天冬酶-3和α-SMA的蛋白质水平。我们的研究结果表明，伊马替尼可能通过凋亡过程发挥卵巢毒性作用，与Cp类似。
