Differentially Expressed Genes in Cisplatin-induced Premature Ovarian Failure in Rats

Background: This study aimed to develop a working animal model for exploring the pathogenesis and molecular mechanisms of premature ovarian failure (POF) as induced by cisplatin.

Methods: Female Sprague-Dawley rats were intraperitoneally injected with different doses of cisplatin. The bodyweight, estrous cyclicity, concentration of gonadal hormones, ovarian weight, and histopathology were determined and compared with those of the control group. Gene chips were used to compare the genes that were differentially expressed between the POF and control ovaries.

Results: A cisplatin dose of 1.5 mg/kg body weight significantly reduced the E2 levels and elevated the gonadotropin levels after two weeks of injection. The treated rats were characterized by estrous cycle disorders and the lack of mature follicles. Thus, these animals could be used as a model for chemotherapy-induced POF. Compared with the controls, the Gene Ontology (GO) categories that were significantly increased in the POF ovaries included "monooxygenase activity," "cholesterol metabolism," and "acute inflammatory response." On the other hand, the GO terms "mitotic spindle organization," "ovulation," and "cholesterol biosynthetic process" were downregulated. The upregulation of three proteins CYP2E1, SCARB1, C3 and downregulation of CYP51 were verified in the cisplatin ovaries by Western blot analysis.

Conclusions: The immune inflammatory response and reactive oxygen species may damage ovarian function in the cisplatin-induced POF.