PMID- 26708340 OWN - NLM STAT- MEDLINE DCOM- 20161020 LR - 20161230 IS - 1872-7654 (Electronic) IS - 0301-2115 (Linking) VI - 196 DP - 2016 Jan TI - Placental NRP1 and VEGF expression in pre-eclamptic women and in a homocysteine-treated mouse model of pre-eclampsia. PG - 69-75 LID - S0301-2115(15)00408-X [pii] LID - 10.1016/j.ejogrb.2015.11.017 [doi] AB - OBJECTIVES: To investigate the expression levels of neuropilin 1 (NRP1) and vascular endothelial growth factor (VEGF) in the placentas of women with pre-eclampsia (PE), determine whether homocysteine (Hcy) contributes to the development of PE in mice, and detect alterations in placental NRP1 and VEGF in Hcy-treated mice. STUDY DESIGN: Placental tissue samples were obtained from 16 patients with and without PE. Using reverse transcription polymerase chain reaction (RT-PCR) and western blot analysis, the expression levels of NRP1 and VEGF in PE and control placental tissues were examined. Immunohistochemical (IHC) assay was used to detect the localization of NRP1 and VEGF proteins. Pregnant mice were treated with DL-Hcy on embryonic day 7.5. The symptoms of the treated mice were examined. The expression levels of Ddah1, Ddah2, eNos, Cbs and Cse were determined by quantitative RT-PCR to study the possible mechanism of hyperhomocysteinemia (HHcy). Nrp1 and Vegf expression levels in the placentas of treated mice were measured by quantitative RT-PCR, western blot analysis and IHC. RESULTS: NRP1 and VEGF were expressed at lower levels in women with PE compared with control women. The immunoreactivity of NRP1 was detected in villous trophoblast cells and villous capillary endothelial cells (ECs). Immunoreactive VEGF was observed mainly in vascular ECs within the villi. The pregnant mice treated with DL-Hcy showed PE-like symptoms such as higher systolic blood pressure and proteinuria in late pregnancy. Compared with the control mice, Ddah1, Ddah2 and eNos mRNA were expressed at lower levels, and Cbs and Cse mRNA were expressed at significantly higher levels in the placentas of the Hcy-treated group. Expression levels of Nrp1 and Vegf in mice placentas were decreased in the Hcy-treated group. CONCLUSIONS: DL-Hcy can induce PE-like symptoms in mice. Both placental NRP1 and VEGF were expressed at lower levels in women with PE and Hcy-treated mice, which may contribute to endothelial damage. CI - Copyright (c) 2015 Elsevier Ireland Ltd. All rights reserved. FAU - Xu, X AU - Xu X AD - Department of Obstetrics and Gynaecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, PR China. FAU - Yang, X-Y AU - Yang XY AD - Department of Obstetrics and Gynaecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, PR China; Institute of Embryo-Fetal Original Adult Disease Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, PR China. FAU - He, B-W AU - He BW AD - Department of Obstetrics and Gynaecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, PR China. FAU - Yang, W-J AU - Yang WJ AD - Department of Obstetrics and Gynaecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, PR China. FAU - Cheng, W-W AU - Cheng WW AD - Department of Obstetrics and Gynaecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, PR China. Electronic address: wwcheng29@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151124 PL - Ireland TA - Eur J Obstet Gynecol Reprod Biol JT - European journal of obstetrics, gynecology, and reproductive biology JID - 0375672 RN - 0 (Vascular Endothelial Growth Factor A) RN - 0LVT1QZ0BA (Homocysteine) RN - 144713-63-3 (Neuropilin-1) SB - IM MH - Adult MH - Animals MH - Disease Models, Animal MH - Female MH - Homocysteine MH - Humans MH - Hyperhomocysteinemia/metabolism MH - Mice MH - Neuropilin-1/*metabolism MH - Placenta/*metabolism MH - Pre-Eclampsia/chemically induced/*metabolism MH - Pregnancy MH - Vascular Endothelial Growth Factor A/*metabolism OTO - NOTNLM OT - Homocysteine OT - Neuropilin 1 OT - Pre-eclampsia OT - Vascular endothelial growth factor EDAT- 2015/12/29 06:00 MHDA- 2016/10/21 06:00 CRDT- 2015/12/29 06:00 PHST- 2015/02/04 00:00 [received] PHST- 2015/06/20 00:00 [revised] PHST- 2015/11/19 00:00 [accepted] PHST- 2015/12/29 06:00 [entrez] PHST- 2015/12/29 06:00 [pubmed] PHST- 2016/10/21 06:00 [medline] AID - S0301-2115(15)00408-X [pii] AID - 10.1016/j.ejogrb.2015.11.017 [doi] PST - ppublish SO - Eur J Obstet Gynecol Reprod Biol. 2016 Jan;196:69-75. doi: 10.1016/j.ejogrb.2015.11.017. Epub 2015 Nov 24.