Imatinib-Induced Hemorrhage in the Corpus Luteum Is Attenuated in Pseudopregnant and Hypophysectomized Rats

Abstract

Imatinib, a tyrosine kinase inhibitor that targets BCR-ABL, platelet-derived growth factor receptors (PDGFRs), and c-KIT, is known to cause rare ovarian hemorrhagic events. This study investigated the mechanisms underlying imatinib-induced hemorrhage in the corpus luteum by comparing normal, pseudopregnant, and hypophysectomized rats. While normal rats treated with imatinib exhibited significant luteal cyst with hemorrhage, this effect was markedly attenuated in pseudopregnant and hypophysectomized rats, whose estrous cycles were halted. Immunohistochemical analysis revealed that imatinib reduced the ratio of α-SMA-positive pericytes to CD31-positive endothelial cells in the corpus luteum of normal rats, but not in the other groups. These findings suggest that the susceptibility of rats to imatinib-induced hemorrhage is linked to active angiogenesis in the early luteal phase. In contrast, resistance is conferred by the stability of luteal capillaries in pseudopregnant and hypophysectomized rats with stable corpus luteum following arrest of the estrous cycle. This study provides new insights into the risk and mechanism of imatinib-induced luteal hemorrhage and suggests that the suppression of ovulation may mitigate this adverse effect in clinical use.