Curcumin exerts a protective effect against premature ovarian failure in mice.

Zhengjie Yan,Daorong Hou,Yuan Zheng,Heling Fu,Qingting Hao,Youjin Dai,Dan Bao,Xiaowei Nie,Yuan Yin,Qin Chen,Yugui Cui

doi:10.1530/jme-17-0214

Abstract

This study was designed to investigate the protective effect of curcumin against d-galactose (d-gal)-induced premature ovarian failure (POF) in mice. A mouse POF model was induced by subcutaneous injection of d-gal (200 mg/kg/day) daily for 42 days. Mice in the curcumin group received both d-gal treatment and intraperitoneal injection of curcumin (100 mg/kg/day) for 42 days. Ovarian function, oxidative stress and apoptosis were evaluated. The P, E2 and SOD levels were higher, and the FSH, LH and MDA levels were significantly lower in the curcumin group than those in the d-gal group. The proportion of primordial follicles was also significantly higher in the curcumin group than that in the d-gal group. In addition, curcumin treatment after d-gal administration resulted in significantly lower Sod2, Cat, 8-OhdG, 4-HNE, NTY and senescence-associated protein P16 expression levels, higher Amh expression levels and less apoptosis in granulosa cells than was observed in the d-gal group. Moreover, the p-Akt, Nrf2 and HO-1 protein expression levels were significantly higher and the apoptosis-related cleaved caspase-3 and -9 protein expression levels were markedly lower in the curcumin group than in the d-gal group. In conclusion, curcumin effectively inhibited d-gal-induced oxidative stress, apoptosis and ovarian injury via a mechanism involving the Nrf2/HO-1 and PI3K/Akt signaling pathways, suggesting that curcumin is a potential protective agent against POF.

Highlights

Premature ovarian failure (POF), called premature ovarian insufficiency (POI), affects approximately 1% of women in the general population, in whom it causes amenorrhea and hypergonadotropic hypoestrogenism before the age of 40 years (Kaufman et al 1988, Waggoner et al 1990, Guerrero et al 2000, Bandyopadhyay et al 2003).the pathological mechanism underlying POF remains unclear
In the POF model induced by d-gal, curcumin treatment significantly decreased the serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels (P < 0.05, Fig. 1A and B) and increased the serum E2 and P levels (P < 0.01, Fig. 1C and D) and the ovarian Amh expression level (P < 0.05, Fig. 1E)
A mouse POF model was successfully induced by d-galactose. d-galactose treatment resulted in increased reactive oxygen species (ROS) and advanced glycation end products (AGEs), increased granulosa cell apoptosis and damaged follicular development

Summary

Introduction

Premature ovarian failure (POF), called premature ovarian insufficiency (POI), affects approximately 1% of women in the general population, in whom it causes amenorrhea and hypergonadotropic hypoestrogenism before the age of 40 years (Kaufman et al 1988, Waggoner et al 1990, Guerrero et al 2000, Bandyopadhyay et al 2003). The pathological mechanism underlying POF remains unclear. The associated ovarian pathology is related to the toxic effects of galactose and its metabolites at both the ovarian and extraovarian levels (Campbell et al 2010a,b, Rubio-Gozalbo et al 2010). There is no effective etiological treatment for POF.

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Results

Conclusion