OBJECTIVE To characterize circulating insulin-like factor 3 (INSL3) in different stages of ovarian insufficiency and its role in the evaluation of premature ovarian insufficiency (POI). DESIGN Retrospective cohort study. SETTING University-based center for reproductive medicine. PATIENT(S) A total of 145 women, including 48 patients with POI (25 IU/L < follicle-stimulating hormone [FSH] ≤40 IU/L), 49 with biochemical POI (bPOI) (10 IU/L < FSH ≤25 IU/L) and 48 age-matched control women with normal ovarian reserve (FSH <10 IU/L), retrospectively included from the reproductive hospital affiliated with Shandong University between 2017 and 2019. INTERVENTION(S) Levels of INSL3 in the serum and follicular fluid assayed with a commercial radioimmunoassay. MAIN OUTCOME MEASURE(S) Level of INSL3 in serum and follicular fluid among control women and patients with bPOI and POI, its association with different ovarian reserve markers, and its predictive value for bPOI and POI. RESULT(S) The serum INSL3 level continuously declined with the progress of ovarian insufficiency. It showed strong negative association with FSH (-0.655) and luteinizing hormone (-0.433), but positively correlated with antimüllerian hormone (0.617), inhibin B (0.400), antral follicle count (0.630), and testosterone (0.180). Additionally, the circulating INSL3 served as a good predictor for bPOI and POI. No statistically significant difference of INSL3 levels in follicular fluid was observed between bPOI patients and control women. CONCLUSION(S) For the first time our study has revealed an INSL3 deficiency in women with POI, indicating that circulating INSL3 could serve as a promising theca-cell specific marker for POI. Future research on the role of INSL3 in modulating follicular development, steroidogenesis, and POI pathogenesis is warranted.

中文翻译：

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新的膜细胞标志物胰岛素样因子 3 与卵巢功能不全有关

目的 表征卵巢功能不全不同阶段的循环胰岛素样因子3（INSL3）及其在卵巢早衰（POI）评估中的作用。设计 回顾性队列研究。设置 大学为基础的生殖医学中心。患者（S）共145名女性，其中POI患者48名（25IU/L<促卵泡激素[FSH]≤40IU/L），生化POI（bPOI）患者49名（10IU/L<FSH≤ 25 IU / L）和48名年龄匹配的卵巢储备正常（FSH <10 IU / L）对照女性，回顾性纳入山东大学附属生殖医院2017-2019年。 干预（S）血清INSL3水平和用商业放射免疫测定法测定的卵泡液。主要观察指标（S）对照女性和bPOI和POI患者血清和卵泡液中INSL3水平、与不同卵巢储备标志物的关系及其对bPOI和POI的预测价值。结果（S）随着卵巢功能不全的进展，血清INSL3水平持续下降。它与 FSH (-0.655) 和黄体生成素 (-0.433) 呈强烈负相关，但与抗苗勒管激素 (0.617)、抑制素 B (0.400)、窦卵泡计数 (0.630) 和睾酮 (0.180) 呈正相关。此外，循环的 INSL3 是 bPOI 和 POI 的良好预测因子。在 bPOI 患者和对照女性之间未观察到卵泡液中 INSL3 水平的统计学显着差异。结论 (S) 我们的研究首次揭示了 POI 女性的 INSL3 缺陷，表明循环中的 INSL3 可以作为有前途的 POI 的膜细胞特异性标记物。需要进一步研究 INSL3 在调节卵泡发育、类固醇生成和 POI 发病机制中的作用。