Department of Obstetrics and Gynecology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-ku, Nagoya, Aichi ZIP 467-8601 , Japan.
Department of Obstetrics and Gynecology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-ku, Nagoya, Aichi ZIP 467-8601 , Japan; Department of Obstetrics and Gynecology, Nagoya City University West Medical Center, 1-1-1 Hirate-cho, Kita-ku, Nagoya, Aichi ZIP 462-8508, Japan.
J Reprod Immunol. 2023 Dec;160:104155. doi: 10.1016/j.jri.2023.104155. Epub 2023 Sep 22.
A recent meta-analysis revealed that patients with unexplained recurrent pregnancy loss (RPL) show higher insulin resistance compared to healthy controls. However, the etiology of RPL remains unknown. Prokineticin (PROK1), a pleiotropic uterine endometrial protein, is important for implantation and decidualization and is regulated by hypoxia and insulin. In this study, we investigated the decidualization status and the role of PROK1 in the decidua of patients with unexplained RPL showing insulin resistance. Thirty-two patients with unexplained RPL were included in this study. Following the diagnosis of a miscarriage, the decidua and villi of the patient were surgically collected. Fasting blood glucose and insulin levels were measured, and HOMA-β was calculated. Using IHC and ELISA, the expression of IGFBP-1, PRL and PROK1 in the decidua and IGF-2 in the villi were analyzed in patients with euploid miscarriage with a high HOMA-β index (n = 8) and compared to controls (euploid miscarriage with normal HOMA-β: n = 12, aneuploid miscarriage with normal HOMA-β: n = 12). The co-localization of PROK1 and IGFBP-1 was observed in the decidua by IHC. In the decidua of RPL patients with high HOMA-β, the expression levels of IGFBP-1 and PRL were significantly lower, whereas the PROK1/IGFBP-1 ratio was significantly higher compared to that of the controls. IGF-2 expression in villi was significantly lower in RPL patients with high HOMA-β. Impaired decidualization and excessive PROK1 production may have pathological implications in patients with unexplained RPL with insulin resistance, especially under the state of hyper insulin production.
一项最近的荟萃分析显示，与健康对照组相比，不明原因复发性妊娠丢失（RPL）患者表现出更高的胰岛素抵抗。然而，RPL 的病因仍然未知。促动力素（PROK1）是一种多效性的子宫内膜蛋白，对于着床和蜕膜化很重要，并且受缺氧和胰岛素调节。在这项研究中，我们研究了表现出胰岛素抵抗的不明原因 RPL 患者的蜕膜化状态和 PROK1 的作用。本研究纳入了 32 名不明原因 RPL 患者。在诊断为流产后，对患者的蜕膜和绒毛进行了手术采集。测量空腹血糖和胰岛素水平，并计算 HOMA-β。通过免疫组化和 ELISA，分析了高 HOMA-β 指数（n=8）的正常核型流产患者和对照组（正常核型流产患者，HOMA-β 正常：n=12，正常核型流产患者，HOMA-β 正常：n=12）蜕膜中 IGFBP-1、PRL 和 PROK1 的表达以及绒毛中 IGF-2 的表达。通过免疫组化观察到 PROK1 和 IGFBP-1 在蜕膜中的共定位。在 HOMA-β 较高的 RPL 患者的蜕膜中，IGFBP-1 和 PRL 的表达水平明显降低，而 PROK1/IGFBP-1 比值明显高于对照组。高 HOMA-β 的 RPL 患者绒毛中 IGF-2 的表达明显降低。蜕膜化受损和 PROK1 过度产生可能与胰岛素抵抗的不明原因 RPL 患者具有病理意义，尤其是在高胰岛素产生的情况下。
