Vitamin D has therapeutic effects on obesity and hyperandrogenemia in PCOS mouse model induced by low dose DHEA and high-fat diet

Abstract

Polycystic ovary syndrome (PCOS) is the most complex and common reproductive endocrine disease among reproductive age women. This study aimed to investigate the effects of vitamin D (Vit.D) in a PCOS mouse model induced by low dose DHEA and high-fat diet. Prepubertal female mice were divided into 4 groups randomly: control, PCOS, PCOS with low dose Vit.D(LDVD), and PCOS with high dose Vit.D(HDVD) groups (n = 10 per group). PCOS mice were administrated with high-fat diet and subcutaneous injection with 6 mg/kg/day dehydroepiandrosterone throughout the study. After the first 30 days, 1,25(OH)2D3 was intend to be administered by intraperitoneal injection for 40 consecutive days, 1.3 µg/kg/week in LDVD group, and 13 µg/kg /week in HDVD group. However, the mice in HDVD group appeared to be fatigue and anorexic after the Vit.D injections, then all died within two weeks. The body weights and testosterone levels in PCOS group were significantly higher than those in the control and LDVD groups (P < 0.001). The total cholesterol levels in the control group were lower than those in PCOS and LDVD groups (P < 0.001). Further, the ratio of liver to body weight was different among groups (P < 0.001). Our data illustrates that Vit.D has therapeutic effects on obesity and hyperandrogenemia in PCOS mouse model induced by low dose DHEA and high-fat diet. However, over dose of Vit.D is toxic. Further researches are needed to elucidate the mechanisms.

Keywords: Hyperandrogenemia; Obesity; Polycystic ovary syndrome; Vitamin D.

Fig. 1

Estrous cycle and ovaries of different groups of mice. (A) Representative estrous cycle pattern from each group. P, proestrus; E, estrus; M, metestrus; D, diestrus. (B) Ovary weight. (C) Ratio of ovary to body weight. (D) Representative H&E staining of ovarian sections. Micrographs were taken at magnifications ×25, ×100, and ×400, and bars = 500, 125, and 31.3 μm, respectively. The boxed areas are shown at higher magnifications. Black asterisk, corpora lutea

Fig. 2

Livers of different groups of mice. (A) Gross morphology. (B) Liver weight. (C) Ratio of liver to body weight. # P < 0.05 vs. control group; ^ P < 0.05 vs. PCOS group. * P < 0.05 vs. LDVD group

Fig. 3

Body weight of different groups of mice. * P < 0.05 vs. control; # P < 0.05 vs. PCOS