CONTEXT: The pathogenic origin of preeclampsia is defective placental development (placentation) and function. Preeclampsia is not diagnosed until later in pregnancy, and reliable early detection is highly desirable. HtrA3 is a recently cloned gene with high expression during placentation in the mouse, rhesus monkey, and human. OBJECTIVE: The present study examined the placental production and the serum profile of HtrA3 across gestation in women, the potential molecular mechanisms regulating HtrA3 production, and the association between maternal HtrA3 serum levels and preeclampsia. METHODS: Immunohistochemistry determined HtrA3 expression pattern and cellular localization in first-, second-, and third-trimester placenta. The maternal serum HtrA3 levels were analyzed by Western blotting. The regulation of placental HtrA3 production and the secretion by oxygen tension was investigated in first-trimester placental explants and trophoblast cells. RESULTS: Placental HtrA3 protein was maximally produced in the first trimester and then dramatically down-regulated, especially in the syncytiotrophoblast. HtrA3 was secreted into the maternal circulation with a serum profile reflecting placental production. Oxygen tension regulated HtrA3; low oxygen enhanced, whereas the transition from low to high oxygen decreased, HtrA3 protein production in syncytiotrophoblast. Maternal serum HtrA3 levels at approximately 13-14 wk of gestation were significantly higher in women who subsequently developed preeclampsia. It appeared that HtrA3 down-regulation was delayed in preeclamptic pregnancies. CONCLUSIONS: HtrA3 protein production is closely associated with changing in oxygen tension in the placenta. The decline in HtrA3 at the end of first trimester may reflect the placental low to high oxygen switch. Abnormally high levels of serum HtrA3 at approximately 13-14 wk of gestation is associated with preeclampsia.
CONTEXT: The pathogenic origin of preeclampsia is defective placental development (placentation) and function. Preeclampsia is not diagnosed until later in pregnancy, and reliable early detection is highly desirable. HtrA3 is a recently cloned gene with high expression during placentation in the mouse, rhesus monkey, and human. OBJECTIVE: The present study examined the placental production and the serum profile of HtrA3 across gestation in women, the potential molecular mechanisms regulating HtrA3 production, and the association between maternal HtrA3 serum levels and preeclampsia. METHODS: Immunohistochemistry determined HtrA3 expression pattern and cellular localization in first-, second-, and third-trimester placenta. The maternal serum HtrA3 levels were analyzed by Western blotting. The regulation of placental HtrA3 production and the secretion by oxygen tension was investigated in first-trimester placental explants and trophoblast cells. RESULTS: Placental HtrA3 protein was maximally produced in the first trimester and then dramatically down-regulated, especially in the syncytiotrophoblast. HtrA3 was secreted into the maternal circulation with a serum profile reflecting placental production. Oxygen tension regulated HtrA3; low oxygen enhanced, whereas the transition from low to high oxygen decreased, HtrA3 protein production in syncytiotrophoblast. Maternal serum HtrA3 levels at approximately 13-14 wk of gestation were significantly higher in women who subsequently developed preeclampsia. It appeared that HtrA3 down-regulation was delayed in preeclamptic pregnancies. CONCLUSIONS:HtrA3 protein production is closely associated with changing in oxygen tension in the placenta. The decline in HtrA3 at the end of first trimester may reflect the placental low to high oxygen switch. Abnormally high levels of serum HtrA3 at approximately 13-14 wk of gestation is associated with preeclampsia.
Authors: Przemyslaw Glaza; Jerzy Osipiuk; Tomasz Wenta; Dorota Zurawa-Janicka; Miroslaw Jarzab; Adam Lesner; Bogdan Banecki; Joanna Skorko-Glonek; Andrzej Joachimiak; Barbara Lipinska Journal: PLoS One Date: 2015-06-25 Impact factor: 3.240
Authors: Michael W Risør; Ebbe Toftgaard Poulsen; Line R Thomsen; Thomas F Dyrlund; Tania A Nielsen; Niels Chr Nielsen; Kristian W Sanggaard; Jan J Enghild Journal: Biochemistry Date: 2014-06-06 Impact factor: 3.162
Authors: Gabor Szalai; Yi Xu; Roberto Romero; Tinnakorn Chaiworapongsa; Zhonghui Xu; Po Jen Chiang; Hyunyoung Ahn; Birgitta Sundell; Olesya Plazyo; Yang Jiang; Mary Olive; Bing Wang; Suzanne M Jacques; Faisal Qureshi; Adi L Tarca; Offer Erez; Zhong Dong; Zoltan Papp; Sonia S Hassan; Edgar Hernandez-Andrade; Nandor Gabor Than Journal: PLoS One Date: 2014-11-13 Impact factor: 3.240
Authors: Gabor Szalai; Roberto Romero; Tinnakorn Chaiworapongsa; Yi Xu; Bing Wang; Hyunyoung Ahn; Zhonghui Xu; Po Jen Chiang; Birgitta Sundell; Rona Wang; Yang Jiang; Olesya Plazyo; Mary Olive; Adi L Tarca; Zhong Dong; Faisal Qureshi; Zoltan Papp; Sonia S Hassan; Edgar Hernandez-Andrade; Nandor Gabor Than Journal: PLoS One Date: 2015-04-10 Impact factor: 3.240