Hong Yeon Hee, Kim Se Jeong, Kim Seul Ki, Lee Seung-Chan, Jun Jin Hyun, Jee Byung Chul, Kim Seok Hyun
Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam, Korea.
Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea.
Clin Exp Reprod Med. 2020 Dec;47(4):269-276. doi: 10.5653/cerm.2020.03755. Epub 2020 Nov 24.
We investigated the impact of tyrosine kinase inhibitor (imatinib or dasatinib) coadministration with cyclophosphamide (Cp) on preantral follicle development in an in vitro mouse model.
Seventy-three female BDF1 mice were allocated into four experimental groups: group A, saline; group B, Cp (25 mg/kg); group C, Cp (25 mg/kg) and imatinib (7.5 mg/kg); and group D, Cp (25 mg/kg) and dasatinib (7.5 mg/kg). Preantral follicles were isolated and cultured in vitro up to 12 days. Final oocyte acquisition and spindle integrity of metaphase II (MII) oocytes were assessed. Levels of 17β-estradiol and anti-Müllerian hormone (AMH) in the final spent media were measured by enzyme-linked immunosorbent assays, and the mRNA levels of Star, Sod1, Mapk3, and Casp3 in the final follicular cells were quantified by real-time polymerase chain reaction.
The percentage of MII oocytes per initiated follicle, the proportion of MII oocytes with normal spindles, and the 17β-estradiol level were similar in all four groups. The median AMH level in group B (7.74 ng/mL) was significantly lower than that in group A (10.84 ng/mL). However, the median AMH levels in group C (9.96 ng/mL) and group D (9.71 ng/mL) were similar to that in group A. The mRNA expression levels of Star, Sod1, Mapk3, and Casp3 were similar in all four groups.
Coadministration of imatinib or dasatinib with Cp could preserve AMH production capacity in this in vitro mice preantral follicle culture model, and it did not affect MII oocyte acquisition.
我们在体外小鼠模型中研究了酪氨酸激酶抑制剂（伊马替尼或达沙替尼）与环磷酰胺（Cp）联合使用对窦前卵泡发育的影响。
将73只雌性BDF1小鼠分为四个实验组：A组，生理盐水；B组，Cp（25mg/kg）；C组，Cp（25mg/kg）和伊马替尼（7.5mg/kg）；D组，Cp（25mg/kg）和达沙替尼（7.5mg/kg）。分离窦前卵泡并在体外培养12天。评估最终卵母细胞的获取情况以及中期II（MII）卵母细胞的纺锤体完整性。通过酶联免疫吸附测定法测量最终培养液中17β-雌二醇和抗苗勒管激素（AMH）的水平，并通过实时聚合酶链反应定量最终卵泡细胞中Star、Sod1、Mapk3和Casp3的mRNA水平。
所有四个组中每个起始卵泡的MII卵母细胞百分比、具有正常纺锤体的MII卵母细胞比例以及17β-雌二醇水平相似。B组的AMH水平中位数（7.74ng/mL）显著低于A组（10.84ng/mL）。然而，C组（9.96ng/mL）和D组（9.71ng/mL）的AMH水平中位数与A组相似。所有四个组中Star、Sod1、Mapk3和Casp3的mRNA表达水平相似。
在这个体外小鼠窦前卵泡培养模型中，伊马替尼或达沙替尼与Cp联合使用可保留AMH的产生能力，并且不影响MII卵母细胞的获取。
