Third Department of Pediatrics, National and Kapodistrian University of Athens, Medical School, University General Hospital "Attikon," GR-12464, Athens, Greece.
Department of Clinical Biochemistry, National and Kapodistrian University of Athens, Medical School, University General Hospital "Attikon," GR-12464, Athens, Greece.
J Clin Endocrinol Metab. 2023 Sep 18;108(10):2666-2675. doi: 10.1210/clinem/dgad164.
The low-density lipoprotein receptor-related protein 5 (LRP5) and its inhibitor sclerostin, are key components of bone metabolism and potential contributors to type 2 diabetes mellitus susceptibility. This study aims at evaluating the expression of placental LRP5 and sclerostin in pregnancies with gestational diabetes mellitus (GDM) and investigate possible associations with umbilical sclerostin concentrations and clinical outcomes in mothers and their neonates.
Twenty-six GDM-mothers and 34 non-GDM mothers of Caucasian origin and their neonates admitted in a gynecology and obstetrics department of a university hospital were included in this study. Demographic data and maternal fasting glucose concentrations (24-28 weeks of gestation) were retrieved from the patients' medical records. Placental LRP5 was determined by immunohistochemistry (IHC) and Western blotting analysis; placental sclerostin was determined by IHC. Umbilical serum sclerostin concentrations were measured by ELISA.
Placental sclerostin IHC intensity values were positively correlated with LRP5 values as detected either by IHC (r = 0.529; P < .001) or Western blotting (r = 0.398; P = .008), with pregestational maternal body mass index values (r = 0.299; P = .043) and with maternal fasting glucose concentrations (r = 0.475; P = .009). Placental sclerostin and LRP5 were significantly greater in GDM compared with non-GDM placentas (histo-score: 65.08 ± 17.09 vs 11.45 ± 2.33, P < .001; 145.53 ± 43.74 vs 202.88 ± 58.65, P < .001; respectively).
Sclerostin and LRP5 were detected in human placentas. The overexpression of placental sclerostin and LRP5 values in GDM compared with non-GDM pregnancies, as well as the positive association of placental sclerostin values with pregestational maternal body mass index and maternal fasting glucose concentrations may indicate the development of an adaptive mechanism in face of maternal hyperglycemia.
低密度脂蛋白受体相关蛋白 5（LRP5）及其抑制剂骨硬化蛋白是骨代谢的关键组成部分，也是 2 型糖尿病易感性的潜在贡献者。本研究旨在评估妊娠期糖尿病（GDM）孕妇胎盘 LRP5 和骨硬化蛋白的表达，并探讨其与脐血清骨硬化蛋白浓度及母婴临床结局的可能相关性。
本研究纳入了 26 名白人 GDM 孕妇和 34 名非 GDM 孕妇及其新生儿。从患者病历中提取人口统计学数据和孕妇空腹血糖浓度（妊娠 24-28 周）。通过免疫组织化学（IHC）和 Western blot 分析检测胎盘 LRP5；通过 IHC 检测胎盘骨硬化蛋白；通过 ELISA 检测脐血清骨硬化蛋白浓度。
胎盘骨硬化蛋白 IHC 强度值与通过 IHC（r = 0.529；P <.001）或 Western blot（r = 0.398；P =.008）检测到的 LRP5 值呈正相关，与孕前母体体重指数值（r = 0.299；P =.043）和母体空腹血糖浓度（r = 0.475；P =.009）呈正相关。GDM 胎盘的骨硬化蛋白和 LRP5 明显高于非 GDM 胎盘（组织评分：65.08 ± 17.09 比 11.45 ± 2.33，P <.001；145.53 ± 43.74 比 202.88 ± 58.65，P <.001；分别）。
在人胎盘组织中检测到了骨硬化蛋白和 LRP5。与非 GDM 妊娠相比，GDM 妊娠中胎盘骨硬化蛋白和 LRP5 的过度表达，以及胎盘骨硬化蛋白值与孕前母体体重指数和母体空腹血糖浓度的正相关，可能表明在面对母体高血糖时，存在一种适应性机制。
