Abstract
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.
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We thank all the patients who participated in this study and staff who assisted with sample collection.
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KRV: Project development, Manuscript writing, Data analysis. DAO: Project development, Data Collection. AEN: Data analysis, Data collection. OAR: Data collection. AON: Manuscript editing. PVO: Manuscript editing. KIM: Manuscript editing.
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Kapustin, R.V., Drobintseva, A.O., Alekseenkova, E.N. et al. Placental protein expression of kisspeptin-1 (KISS1) and the kisspeptin-1 receptor (KISS1R) in pregnancy complicated by diabetes mellitus or preeclampsia. Arch Gynecol Obstet 301, 437–445 (2020). https://doi.org/10.1007/s00404-019-05408-1
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DOI: https://doi.org/10.1007/s00404-019-05408-1