Placental protein expression of kisspeptin-1 (KISS1) and the kisspeptin-1 receptor (KISS1R) in pregnancy complicated by diabetes mellitus or preeclampsia
Placental protein expression of kisspeptin-1 (KISS1) and the kisspeptin-1 receptor (KISS1R) in pregnancy complicated by diabetes mellitus or preeclampsia
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DOI：
10.1007/s00404-019-05408-1
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发表时间：
2020-02-01
影响因子：
2.6
通讯作者：
Kvetnoy, I. M.
中科院分区：
文献类型：
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作者：
Kapustin, R. V.;Drobintseva, A. O.;Kvetnoy, I. M.
目的Kisspeptins调节滋养细胞侵袭。这一过程的紊乱可能导致先兆子痫（PE）的发生。糖尿病（DM）与该并发症的高发生率相关。主要假设是研究糖尿病、先兆子痫和健康妊娠中kisspeptin-1（KISS 1）及其受体（KISS 1 R）的胎盘蛋白表达。方法将65例胎盘分为以下几组：对照组（n = 20），PE或非PE 1型糖尿病（T1 DM）（n = 10），PE或非PE 2型糖尿病（T2 DM）（n = 10），PE或非PE妊娠糖尿病（GDM）（n = 10）和无糖尿病的先兆子痫（PE）（n = 15）。免疫组化分析用于证明KISS 1/KISS 1 R在胎盘组织中的存在和定位，并测量免疫阳性表达的面积。进行相关性分析，以检测这些生物标志物的蛋白质表达和主要产科结局之间的联系。结果KISS 1在PE组和GDM组胎盘组织中的表达率最高，分别为35.4%和33.2%。在糖尿病患者中，KISS 1的表达水平依赖于PE的存在，并且高于糖尿病无PE组和对照组：T1 DM + PE组为30.6%，T2 DM + PE组为30.1%。在对照组中检测到最低表达（14.1%）。KISS 1 R在DM和PE中的表达高于对照组。我们检测到PE与KISS 1（r = 0.81）和KISS 1 R（r = 0.56）的胎盘表达之间的强直接联系，以及KISS 1与早产出生体重之间的负相关联系（r =-0.73）。KISS 1与IUGR（r = 0.29）和早产（r = 0.24）之间存在低相关性。KISS 1 R检测到相同的趋势。我们没有发现胎盘表达KISS/KISS 1 R与胎盘重量或HbA 1c水平之间存在任何显著相关性。结论糖尿病患者胎盘组织中KISS 1和KISS 1 R的表达水平升高，可能参与了胎盘形成过程的改变，导致子痫前期的发生。
Purpose Kisspeptins regulate the trophoblast invasion. The disturbance of this process might lead to the development of preeclampsia (PE). Diabetes mellitus (DM) is associated with the high rate of this complication. The main hypothesis was to investigate the placental protein expression of kisspeptin-1 (KISS1) and its receptor (KISS1R) in diabetic, preeclamptic, and healthy pregnancies. Methods Placentae (n = 65) were divided into the following groups: the control group (n = 20), either PE or non-PE type-1 diabetes mellitus (T1DM) (n = 10), either PE or non-PE type-2 diabetes mellitus (T2DM) (n = 10), either PE or non-PE gestational diabetes mellitus (GDM) (n = 10) and preeclampsia without diabetes (PE) (n = 15). Immunohistochemistry analysis was used for demonstrating the presence and location of KISS1/KISS1R in placental tissue and to measure the area of immunopositive expression. Correlation analyses were performed to detect the links between protein expression of these biomarkers and the main obstetric outcomes. Results The highest placental protein expressions of KISS1 were detected in the PE (35.4%) and GDM (33.2%) groups. In case of DM, levels of KISS1 expression depended on the presence of PE and were higher compared with DM no PE and control groups: (30.6%) in T1DM + PE and (30.1%) in T2DM + PE group. The lowest expression was detected in the control group (14.1%). The expression of KISS1R was higher in DM and PE compared to the control group. We detected the strong direct link between PE and placental expression of KISS1 (r = 0.81) and KISS1R (r = 0.56), and inverse correlation link between KISS1 and preterm birth weight (r = - 0.73). The low correlation links were found between KISS1 and IUGR (r = 0.29), and preterm birth (r = 0.24). The same trend was detected for KISS1R. We did not find any significant correlations between placental expressions of KISS/KISS1R and placental weight or HbA1c levels. Conclusion Increased expression levels of KISS1 and KISS1R in case of diabetes mellitus may play a role in the altered placentation process and lead to the development of preeclampsia.