Protective effects of dichloroacetic acid on endometrial injury and ovarian reserve in an experimental rat model of diabetes mellitus

Abstract

Aim To study (1) ovarian and endometrial damage caused by the hyperglycemia and (2) the effects of dichloroacetic acid (DCA) on follicular reserve and endometrial damage in streptozocin induced diabetic rats. Methods This study consisted 24 rats randomly separated into three groups. A diabetes model was achieved in 16 rats experimentally, and normoglycemic eight rats were assigned as control group (Group 1). The rats with diabetes were randomly separated to two groups: 1 mL/kg/day intraperitoneal 0.9% NaCl was given to eight rats as diabetic vehicle (Group 2) and 10 mg/kg/day DCA was given to other eight rats as DCA treated group (Group 3). Hysterectomy with bilateral oophorectomy was performed for histopathological evaluation and blood samples were collected after 4 weeks. Results Diabetes caused ovarian and endometrial damage (p < 0.0001). Pentraxin-3 (PTX-3), lactic acid, and transforming growth factor-beta (TGF-beta) were higher (p < 0.05, p < 0.05, and p < 0.0001, respectively), whereas anti-Mullerian hormone (AMH) was lower in diabetic rats (p < 0.05). These findings reflected the diabetic damage in the genital tract and diminished ovarian reserve occurred via fibrosis, severe inflammation, and oxidative stress. DCA improved the histopathological fibrosis and degeneration in the ovaries and endometrium (p < 0.05). There was a concominant decrease of TGF-beta and lactic acid levels with DCA treatment (p < 0.05). DCA also improved ovarian reserve with higher AMH levels (p < 0.05). Conclusions The several unfavored changes in the endometrium and ovaries due to diabetes have been determined in this present study. DCA might provide the continuity of the endometrial cycle, physiological endometrial structure, ovarian follicular growth, oocyte maturation, and physiological ovarian function by decreasing the lactate levels via inhibiting pyruvate dehydrogenase kinase enzyme.