One of the major reasons for implantation failure and spontaneous abortion is a high incidence of preimplantation chromosomal aneuploidy. Lapatinib simultaneously inhibits EGFR and HER2, leading to apoptosis. We hypothesized a higher sensitivity for aneuploid cells in preimplantation embryos to lapatinib based on reports of aneuploid cell lines being sensitive to some anticancer drugs. Late 2-cell mouse embryos were treated with lapatinib after determining a nontoxic dose. Morphologies were recorded 24, 48, and 60 hours later. The effect of lapatinib on the aneuploidy rate was evaluated by studying blastocyst cells using FISH. Although the rate of development to 8-cell and morula stage was higher in the control group (p < 0.05), there was no difference in development to the blastocyst stage at the same studied intervals between lapatinib-treated and control groups (p = 0.924). The mean number of cells in morula and blastocyst stages were not different between the groups (p = 0.331 and p = 0.175, respectively). The frequency of aneuploid cells and diploid embryos was, respectively, significantly lower and higher in lapatinib-treated embryos, (p < 0.001). Since lapatinib treatment reduced the aneuploidy rate without impact on the development of mouse preimplantation embryos to the blastocyst stage and number of total cells, lapatinib seems useful for prevention of preimplantation aneuploidy in in vitro fertilization.

中文翻译：

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拉帕替尼降低体外受精小鼠胚胎的着床前非整倍体率而不影响着床前发育的完成

着床失败和自然流产的主要原因之一是着床前染色体非整倍体的发生率高。拉帕替尼同时抑制 EGFR 和 HER2，导致细胞凋亡。根据非整倍体细胞系对某些抗癌药物敏感的报告，我们假设植入前胚胎中的非整倍体细胞对拉帕替尼具有更高的敏感性。在确定无毒剂量后，用拉帕替尼处理晚期 2 细胞小鼠胚胎。24、48 和 60 小时后记录形态。通过使用 FISH 研究囊胚细胞来评估拉帕替尼对非整倍体率的影响。虽然对照组发展到 8 细胞和桑椹期的速度较高（p < 0.05），在相同的研究时间间隔内，拉帕替尼治疗组和对照组之间发育到囊胚阶段没有差异（p = 0.924）。桑椹胚和胚泡阶段的平均细胞数在​​各组之间没有差异（分别为 p = 0.331 和 p = 0.175）。在拉帕替尼处理的胚胎中，非整倍体细胞和二倍体胚胎的频率分别显着降低和升高（p < 0.001）。由于拉帕替尼治疗降低了非整倍体率而不影响小鼠植入前胚胎发育至囊胚阶段和总细胞数，因此拉帕替尼似乎可用于预防体外受精中的植入前非整倍体。分别）。在拉帕替尼处理的胚胎中，非整倍体细胞和二倍体胚胎的频率分别显着降低和升高（p < 0.001）。由于拉帕替尼治疗降低了非整倍体率而不影响小鼠植入前胚胎发育至囊胚阶段和总细胞数，因此拉帕替尼似乎可用于预防体外受精中的植入前非整倍体。分别）。在拉帕替尼处理的胚胎中，非整倍体细胞和二倍体胚胎的频率分别显着降低和升高（p < 0.001）。由于拉帕替尼治疗降低了非整倍体率而不影响小鼠植入前胚胎发育至囊胚阶段和总细胞数，因此拉帕替尼似乎可用于预防体外受精中的植入前非整倍体。