Department of Obstetrics and Gynecology, Yamagata University Faculty of Medicine, Yamagata 990-9585, Japan.
J Ovarian Res. 2013 Sep 30;6(1):69. doi: 10.1186/1757-2215-6-69.
Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age and is characterized by chronic anovulation. Insulin resistance may be a key component of the pathogenesis of this disorder. Pioglitazone is a thiazolidinedione derivative that acts by improving insulin resistance via the peroxisome proliferator-activated receptor-γ (PPAR-γ) pathway. Reportedly, pioglitazone improves the anovulation status in patients with PCOS. In the present study, we examined whether pioglitazone directly affects ovarian follicular development and steroidogenesis using in vitro mouse preantral follicle culture system.
An isolated individual in vitro mouse preantral follicle culture was used to test the effects of pioglitazone on the follicle development and steroidogenesis. Tumor necrosis factor-α (TNF-α), which plays a role in insulin resistance, has been reported to inhibit the follicle stimulating hormone (FSH)-induced follicular development and steroidogenesis in an in vitro mouse preantral follicle culture system. Therefore, we examined whether pioglitazone counteracts these effects by TNF-α. We assessed the follicle diameter and follicle survival and antral-like cavity formation rates, the 17β-estradiol (E2) levels in the culture medium, and the ovulation rate using the in vitro preantral follicle culture.
Pioglitazone treatment counteracted the inhibition of TNF-α in FSH-induced follicle development in a dose-dependent manner. Pioglitazone, at a concentration of 5 μM, which was the minimum effective concentration, significantly counteracted the inhibition of TNF-α in FSH-induced follicle survival (29 versus 56%, P < 0.05), antral-like cavity formation (29 versus 48%, P < 0.05), E2 concentration in the culture medium (mean ± SEM = 21 ± 1 versus mean ± SEM = 27 ± 1 pg/mL, P < 0.05), and human chorionic gonadotropin-induced ovulation rate (9 versus 28%, P < 0.05).
Pioglitazone counteracted the inhibition by TNF-α on FSH-induced follicle development and steroidogenesis in the in vitro mouse preantral follicle culture. The results suggest that pioglitazone may directly affect the follicular development and steroidogenesis.
多囊卵巢综合征（PCOS）是一种常见的育龄期女性内分泌疾病，其特征为慢性无排卵。胰岛素抵抗可能是这种疾病发病机制的关键组成部分。吡格列酮是一种噻唑烷二酮衍生物，通过过氧化物酶体增殖物激活受体-γ（PPAR-γ）通路改善胰岛素抵抗。据报道，吡格列酮可改善 PCOS 患者的无排卵状态。在本研究中，我们使用体外小鼠原始卵泡培养系统，研究了吡格列酮是否直接影响卵巢卵泡发育和类固醇生成。
使用分离的体外小鼠原始卵泡培养来测试吡格列酮对卵泡发育和类固醇生成的影响。肿瘤坏死因子-α（TNF-α）在胰岛素抵抗中起作用，据报道，它可抑制体外小鼠原始卵泡培养系统中卵泡刺激素（FSH）诱导的卵泡发育和类固醇生成。因此，我们研究了吡格列酮是否可以通过 TNF-α来拮抗这些作用。我们评估了卵泡直径和卵泡存活率以及腔形成率、培养基中的 17β-雌二醇（E2）水平以及体外原始卵泡培养的排卵率。
吡格列酮治疗以剂量依赖性方式拮抗 TNF-α对 FSH 诱导的卵泡发育的抑制作用。吡格列酮的最低有效浓度 5μM 可显著拮抗 TNF-α对 FSH 诱导的卵泡存活率（29%对 56%，P<0.05）、腔形成（29%对 48%，P<0.05）、培养基中 E2 浓度（平均值±SEM=21±1 对平均值±SEM=27±1pg/mL，P<0.05）和人绒毛膜促性腺激素诱导的排卵率（9%对 28%，P<0.05）的抑制作用。
吡格列酮拮抗 TNF-α对体外小鼠原始卵泡培养中 FSH 诱导的卵泡发育和类固醇生成的抑制作用。结果表明，吡格列酮可能直接影响卵泡发育和类固醇生成。
