VEGF Maintains Maternal Vascular Space Homeostasis in the Mouse Placenta through Modulation of Trophoblast Giant Cell Functions
Vascular endothelial growth factor (VEGF) is an angiogenic growth factor that acts primarily on endothelial cells, but numerous studies suggest that VEGF also acts on non-endothelial cells, including trophoblast cells. Inhibition of VEGF signaling by excess production of the endogenous soluble VEGF...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-07-01
|
| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/11/7/1062 |
| _version_ | 1797527557823791104 |
|---|---|
| author | Xiujun Fan Shanmugam Muruganandan Philemon D Shallie Sabita Dhal Matthew Petitt Nihar R Nayak |
| author_facet | Xiujun Fan Shanmugam Muruganandan Philemon D Shallie Sabita Dhal Matthew Petitt Nihar R Nayak |
| author_sort | Xiujun Fan |
| collection | DOAJ |
| description | Vascular endothelial growth factor (VEGF) is an angiogenic growth factor that acts primarily on endothelial cells, but numerous studies suggest that VEGF also acts on non-endothelial cells, including trophoblast cells. Inhibition of VEGF signaling by excess production of the endogenous soluble VEGF receptor sFlt1 in trophoblast cells has been implicated in several pregnancy complications. Our previous studies and other reports have shown that VEGF directly regulates placental vascular development and functions and that excess VEGF production adversely affects placental vascular development. Trophoblast giant cells (TGCs) line the maternal side of the placental vasculature in mice and function like endothelial cells. In this study, we specifically examined the effect of excess VEGF signaling on TGC development associated with defective placental vascular development using two mouse models an endometrial VEGF overexpression model and a placenta-specific sFlt1 knockdown model. Placentas of endometrial VEGF-overexpressing dams at embryonic days (E) 11.5 and 14.5 showed dramatic enlargement of the venous maternal spaces in junctional zones. The size and number of the parietal TGCs that line these venous spaces in the placenta were also significantly increased. Although junctional zone venous blood spaces from control and VEGF-overexpressing dams were not markedly different in size at E17.5, the number and size of P-TGCs were both significantly increased in the placentas from VEGF-overexpressing dams. In sFlt1 knockdown placentas, however, there was a significant increase in the size of the sinusoidal TGC-lined, alkaline phosphatase-positive maternal blood spaces in the labyrinth. These results suggest that VEGF signaling plays an important role in maintaining the homeostasis of the maternal vascular space in the mouse placenta through modulation of TGC development and differentiation, similar to the effect of VEGF on endothelial cells in other vascular beds. |
| first_indexed | 2024-03-10T09:45:24Z |
| format | Article |
| id | doaj.art-cac8792f80584901a795739b32dcfe95 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T09:45:24Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-cac8792f80584901a795739b32dcfe952023-11-22T03:19:39ZengMDPI AGBiomolecules2218-273X2021-07-01117106210.3390/biom11071062VEGF Maintains Maternal Vascular Space Homeostasis in the Mouse Placenta through Modulation of Trophoblast Giant Cell FunctionsXiujun Fan0Shanmugam Muruganandan1Philemon D Shallie2Sabita Dhal3Matthew Petitt4Nihar R Nayak5Laboratory of Reproductive Health, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, ChinaDepartment of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USADepartment of Obstetrics and Gynecology, UMKC School of Medicine, Kansas City, MO 64108, USADepartment of Obstetrics and Gynecology, UMKC School of Medicine, Kansas City, MO 64108, USADepartment of Obstetrics and Gynecology, UMKC School of Medicine, Kansas City, MO 64108, USADepartment of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USAVascular endothelial growth factor (VEGF) is an angiogenic growth factor that acts primarily on endothelial cells, but numerous studies suggest that VEGF also acts on non-endothelial cells, including trophoblast cells. Inhibition of VEGF signaling by excess production of the endogenous soluble VEGF receptor sFlt1 in trophoblast cells has been implicated in several pregnancy complications. Our previous studies and other reports have shown that VEGF directly regulates placental vascular development and functions and that excess VEGF production adversely affects placental vascular development. Trophoblast giant cells (TGCs) line the maternal side of the placental vasculature in mice and function like endothelial cells. In this study, we specifically examined the effect of excess VEGF signaling on TGC development associated with defective placental vascular development using two mouse models an endometrial VEGF overexpression model and a placenta-specific sFlt1 knockdown model. Placentas of endometrial VEGF-overexpressing dams at embryonic days (E) 11.5 and 14.5 showed dramatic enlargement of the venous maternal spaces in junctional zones. The size and number of the parietal TGCs that line these venous spaces in the placenta were also significantly increased. Although junctional zone venous blood spaces from control and VEGF-overexpressing dams were not markedly different in size at E17.5, the number and size of P-TGCs were both significantly increased in the placentas from VEGF-overexpressing dams. In sFlt1 knockdown placentas, however, there was a significant increase in the size of the sinusoidal TGC-lined, alkaline phosphatase-positive maternal blood spaces in the labyrinth. These results suggest that VEGF signaling plays an important role in maintaining the homeostasis of the maternal vascular space in the mouse placenta through modulation of TGC development and differentiation, similar to the effect of VEGF on endothelial cells in other vascular beds.https://www.mdpi.com/2218-273X/11/7/1062placentaVEGFsFlt1TGC |
| spellingShingle | Xiujun Fan Shanmugam Muruganandan Philemon D Shallie Sabita Dhal Matthew Petitt Nihar R Nayak VEGF Maintains Maternal Vascular Space Homeostasis in the Mouse Placenta through Modulation of Trophoblast Giant Cell Functions Biomolecules placenta VEGF sFlt1 TGC |
| title | VEGF Maintains Maternal Vascular Space Homeostasis in the Mouse Placenta through Modulation of Trophoblast Giant Cell Functions |
| title_full | VEGF Maintains Maternal Vascular Space Homeostasis in the Mouse Placenta through Modulation of Trophoblast Giant Cell Functions |
| title_fullStr | VEGF Maintains Maternal Vascular Space Homeostasis in the Mouse Placenta through Modulation of Trophoblast Giant Cell Functions |
| title_full_unstemmed | VEGF Maintains Maternal Vascular Space Homeostasis in the Mouse Placenta through Modulation of Trophoblast Giant Cell Functions |
| title_short | VEGF Maintains Maternal Vascular Space Homeostasis in the Mouse Placenta through Modulation of Trophoblast Giant Cell Functions |
| title_sort | vegf maintains maternal vascular space homeostasis in the mouse placenta through modulation of trophoblast giant cell functions |
| topic | placenta VEGF sFlt1 TGC |
| url | https://www.mdpi.com/2218-273X/11/7/1062 |
| work_keys_str_mv | AT xiujunfan vegfmaintainsmaternalvascularspacehomeostasisinthemouseplacentathroughmodulationoftrophoblastgiantcellfunctions AT shanmugammuruganandan vegfmaintainsmaternalvascularspacehomeostasisinthemouseplacentathroughmodulationoftrophoblastgiantcellfunctions AT philemondshallie vegfmaintainsmaternalvascularspacehomeostasisinthemouseplacentathroughmodulationoftrophoblastgiantcellfunctions AT sabitadhal vegfmaintainsmaternalvascularspacehomeostasisinthemouseplacentathroughmodulationoftrophoblastgiantcellfunctions AT matthewpetitt vegfmaintainsmaternalvascularspacehomeostasisinthemouseplacentathroughmodulationoftrophoblastgiantcellfunctions AT niharrnayak vegfmaintainsmaternalvascularspacehomeostasisinthemouseplacentathroughmodulationoftrophoblastgiantcellfunctions |