Progesterone decreases the extent of ovarian damage caused by cisplatin in an experimental rat model

Abstract

Background: Apart from the role of progesterone in reproductive physiology, the protective role of exogenously administered progesterone was observed in various injuries, such as neurologic defects and acute kidney injury.

Objectives: The aim of the present study was to investigate the effects of progesterone therapy on the immunoexpression of anti-Müllerian hormone (AMH) and the number of apoptotic cells in ovarian damage induced with cisplatin, a chemotherapeutic agent, in an experimental rat model.

Material and methods: Forty rats were randomly divided into 4 groups; the control group (the saline group), the cisplatin-treated group (rats were injected with 5 mg/kg/week cisplatin intraperitoneally (i.p.)), the cisplatin + progesterone-treated group (the rats were pretreated with 8 mg/kg progesterone intramuscularly (i.m.) (8 mg/kg) before they were injected with 5 mg/kg/week cisplatin i.p.), and the progesteronetreated group (the rats were treated with 8 mg/kg progesterone i.m.). The ovaries were removed from the rats in all groups 5 days after the final injection of cisplatin.

Results: Histopathologic examination and follicle counting were performed. The immunoreactivity intensity of AMH and apoptosis were compared. Histological analysis of the ovaries treated with cisplatin showed ovarian damage. Immunohistochemical analysis showed that the immunoreactivity intensity of AMH, a biomarker that discriminates the degree of ovarian damage, was lower in the cisplatin-treated groups than in other groups. Terminal deoxynucleotide transferase-mediated 20-deoxyuridine 50-triphosphate nick endlabeling (TUNEL) assays showed that the increase in the number of apoptotic cells was statistically significant in the cisplatin-treated group compared to the control group (p < 0.05). Progesterone administration with cisplatin resulted in decreases in TUNEL-positive cells. The decrease in the number of apoptotic cells was statistically significant in the cisplatin + progesterone-treated group compared to the control group (p < 0.001).

Conclusions: Our results showed that using progesterone as an adjuvant agent against ovarian damage in patients undergoing cancer chemotherapy with cisplatin is beneficial.

Keywords: anti-Müllerian hormone; apoptosis; cisplatin; ovarian damage; progesterone.