Synergic effect of bee pollen and metformin on proliferation and apoptosis of granulosa cells: Rat model of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most common cause of infertility associated with metabolic complications. Several classes of pharmacological agents have been used to manage PCOS. These drugs have shown adverse effects. Various studies showed the bee pollen (BP) as a substance rich in phytoestrogens. This study aimed to investigate the effects of BP and metformin alone and in combination with proliferation and apoptosis of granulosa cells in the rat model of PCOS. In this experimental study, 54 Wistar rats (180-210 g), was injected 2 mg of estradiol valerate intramuscularly and six rats were considered as control. After 60 days, the rats were divided into control, sham, and experimental groups. The rats were treated with bee pollen (50, 100, and 200 mg/kg) and metformin (300 mg/kg), either individually or in combination. Ovarian histology assessment was examined by H&E staining. The serum levels of NO and TNF-α were evaluated. The expressions of P53 and Ki67 were measured by IHC. In the BP and metformin-treated PCOS group, the preantral and antral follicles increased, and cystic follicles significantly decreased (p < .01). The levels of TNF-α, NO, as well as the expressions of Ki67 were decreased in the treated groups compared to the PCOS group (p < .01). On the contrary, apoptosis increased in the groups treated with BP compared to the untreated group (p < .01). BP individually or synergistically with metformin improved the symptoms of PCOS.