Abstract:

Objective  To study the effect of cisplatin on ovarian structure and function in rats and its possible molecular mechanism. Methods  Three-month-old SD female rats were divided into control group (C group, n=5) and chemotherapy group (H group, n=5). Rats in H group were given intraperitoneal injection of cisplatin 2 mg/（kg.d）, rats in C group were given intraperitoneal injection of equal volume of saline. After 7 days continuous injection, rat ovarian index (ovarian wet weight / body weight) was measured. The levels of serum estradiol (E₂) and follicle stimulating hormone (FSH) were tested by enzyme-linked immunosorbent assay (ELISA). The follicle development was observed by hematoxylin-eosin staining. The expression of Smad2, p-Smad2, Smad3, p-Smad3, Smad4 and Smad7 proteins/mRNAs in ovary tissue were detected by immunohistochemistry and Real-time PCR. Results  Compared with C group, the ovarian volume in H group was decreased and the number of growing follicles was significantly decreased (P<0.05). The ovarian index decreased (P<0.05), and the levels of E₂ and FSH in serum increased (P<0.05). Immunohistochemistry and Real-time PCR showed that Smad2 (p-Smad2), Smad3 (p-Smad3), Smad4 and Smad7 were expressed in ovarian follicles at all levels, and the expression of Smad2 protein and mRNA in H group increased (P<0.05). The expressions of Smad3, Smad4 and Smad7 protein and mRNA were decreased (P<0.05), and the expression of P-Smad3 was decreased (P<0.05). Conclusion  Cisplatin-induced follicle injury in rats promotes premature ovarian failure, which result in the increase of Smad2 expression, and decrease of Smad3 and Smad7 expression in the follicle cells. The Smad intracellular signal pathway is involved in the process of chemotherapy ovarian injury.

Key words: Cisplatin, Premature ovarian failure, Smad2(p-Smad2)/Smad3(p-Smad3), Smad4, Smad7, Immunohistochemistry, Real-time PCR, Rat