Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China.
Key laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China.
Front Endocrinol (Lausanne). 2022 May 20;13:874987. doi: 10.3389/fendo.2022.874987. eCollection 2022.
Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disease characterized by irregular menstrual, hyperandrogenism, and polycystic ovaries. The definitive mechanism of the disorder is not fully elucidated. Store-operated Ca2+ entry (SOCE) plays a role in glucose and lipid metabolism, inflammation, hormone secretion, and cell proliferation. STIMs and Orais are the main elements of SOCE. The potential role of SOCE in PCOS pathogenesis remains unclear.
The expression of STIMs and Orais in granulosa cells (GCs) derived from 83 patients with PCOS and 83 controls were analyzed, respectively, by using quantitative reverse transcription polymerase chain reaction. Binary regression analysis was used to identify the factors affecting PCOS after adjusted by body mass index and age. Pearson correlation analysis was used to determine the association between PCOS phenotypes and SOCE genes expression.
Significantly increased expression of STIM1, STIM2, Orai1, and Orai2 were observed in patients with PCOS compared with controls ( = 0.037, = 0.004, ≤ 0.001, and = 0.013, respectively), whereas the expression of Orai3 was decreased ( = 0.003). In addition, the expression levels of STIMs and Orais were identified as the factors affecting PCOS ( < 0.05). The expressions of these genes were correlated with hormone level and antral follicle count ( < 0.05).
For the first time, our findings indicated that the elements of SOCE were differently expressed, where STIM1, STIM2, Orai1, and Orai2 significantly increased, whereas Orai3 decreased in PCOS GCs, which might be dominantly involved in dysfunction of ovarian GCs and hormonal changes in PCOS.
多囊卵巢综合征（PCOS）是一种异质性内分泌疾病，其特征为月经不规律、高雄激素血症和多囊卵巢。该疾病的确切机制尚未完全阐明。钙库操纵的钙内流（SOCE）在葡萄糖和脂质代谢、炎症、激素分泌和细胞增殖中发挥作用。STIMs 和 Orais 是 SOCE 的主要元素。SOCE 在 PCOS 发病机制中的潜在作用尚不清楚。
采用实时定量逆转录聚合酶链反应分别分析 83 例 PCOS 患者和 83 例对照患者来源的颗粒细胞（GCs）中 STIMs 和 Orais 的表达。采用二元回归分析，在调整体重指数和年龄后，确定影响 PCOS 的因素。采用 Pearson 相关性分析，确定 PCOS 表型与 SOCE 基因表达之间的关系。
与对照组相比，PCOS 患者的 STIM1、STIM2、Orai1 和 Orai2 表达明显增加（ = 0.037、 = 0.004、 ≤ 0.001 和 = 0.013，分别），而 Orai3 的表达则降低（ = 0.003）。此外，STIMs 和 Orais 的表达水平被确定为影响 PCOS 的因素（ < 0.05）。这些基因的表达与激素水平和窦卵泡计数相关（ < 0.05）。
我们的研究结果首次表明，SOCE 的各组成部分表达不同，其中 STIM1、STIM2、Orai1 和 Orai2 显著增加，而 Orai3 减少，这可能主要参与卵巢 GC 功能障碍和 PCOS 中的激素变化。
