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Published on: January 26, 2024
Differential expression of human placental PAPP-A2 over gestation and in preeclampsia
Anita W Kramer1, Leah M Lamale-Smith1, Virginia D Winn1
1University of Colorado School of Medicine, Department of Obstetrics and Gynecology, 12631 E. 17th Avenue, Aurora, CO, USA.
Insights
Pregnancy Associated Plasma Protein A2 (PAPP-A2) is elevated in preeclampsia. This study shows PAPP-A2 is increased in placental tissue and maternal serum, but not fetal cord blood, in preeclamptic pregnancies.
Area of Science:
- Reproductive biology
- Endocrinology
- Obstetrics
Background:
- Pregnancy Associated Plasma Protein A2 (PAPP-A2) is an insulin-like growth factor binding protein-5 (IGFBP-5) protease.
- PAPP-A2 is known to be elevated in preeclampsia.
- Insulin-like growth factors are crucial for human implantation and placentation.
Purpose of the Study:
- To determine the expression pattern of PAPP-A2 during human gestation.
- To compare PAPP-A2 expression in normal and preeclamptic pregnancies.
- To evaluate the role of PAPP-A2 in placental development and preeclampsia pathogenesis.
Main Methods:
- Collected placental basal plate and chorionic villi samples, and maternal/fetal cord blood sera from preeclamptic and control pregnancies.
- Performed immunohistochemical staining for cytokeratin-7, HLA-G, and PAPP-A2 on placental tissues.
- Conducted PAPP-A2 immunoblot analysis on placental protein lysates and sera.
Main Results:
- PAPP-A2 is primarily expressed by differentiated trophoblasts and fetal endothelium.
- PAPP-A2 expression in chorionic villi is high in the first trimester, decreases in the second, and reappears in the third.
- PAPP-A2 levels are increased in placental tissues and maternal sera of preeclamptic pregnancies but absent in cord blood.
Conclusions:
- PAPP-A2 exhibits differential expression in trophoblast populations and is downregulated in the mid-second trimester.
- Preeclampsia is associated with increased maternal serum and placental PAPP-A2 levels.
- PAPP-A2 alterations in preeclampsia are confined to the maternal-placental unit and not reflected in fetal circulation.
Introduction:
Pregnancy Associated Plasma Protein A2 (PAPP-A2) is a pregnancy related insulin-like growth factor binding protein-5 (IGFBP-5) protease, known to be elevated in preeclampsia. As the insulin-like growth factors are important in human implantation and placentation, we sought to determine the expression pattern of PAPP-A2 over human gestation in normal and preeclamptic pregnancies to evaluate its role in placental development and the pathogenesis of preeclampsia.
Methods:
Placental basal plate and chorionic villi samples, maternal and fetal cord blood sera were obtained from preeclamptic and control pregnancies. Formalin-fixed tissue sections from across gestation were stained for cytokeratin-7, HLA-G, and PAPP-A2. PAPP-A2 immunoblot analysis was also performed on protein lysates and sera.
Results:
PAPP-A2 expression is predominately expressed by differentiated trophoblasts and fetal endothelium. Chorionic villi show strong expression in the first trimester, followed by a progressive decrease in the second trimester, which returns in the third trimester. PAPP-A2 expression is not impacted by labor. PAPP-A2 is increased in the basal plate, chorionic villi and maternal sera in preeclampsia compared to controls, but is not detectable in cord blood.
Discussion:
PAPP-A2 is differentially expressed in different trophoblast populations and shows strong down regulation in the mid second trimester in chorionic villous samples. Both maternal sera and placental tissue from pregnancies complicated by preeclampsia show increased levels of PAPP-A2. PAPP-A2 levels are not altered by labor. Additionally, PAPP-A2 cannot be detected in cord blood demonstrating that the alterations in maternal and placental PAPP-A2 are not recapitulated in the fetal circulation.
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