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Mtnr1b deletion disrupts placental angiogenesis through the VEGF signaling pathway leading to fetal growth restriction.
Wang, Likai; Han, Qi; Yan, Laiqing; Ma, Xiao; Li, Guangdong; Wu, Hao; Liu, Yunjie; Chen, Huiling; Ji, Pengyun; Wang, Bingyuan; Zhang, Ran; Liu, Guoshi.
Afiliación
  • Wang L; National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agricultural, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, China.
  • Han Q; Liver Research Center, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong'an Road, Xicheng District, Beijing, China.
  • Yan L; National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agricultural, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, China.
  • Ma X; National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agricultural, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, China.
  • Li G; National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agricultural, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, China.
  • Wu H; National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agricultural, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, China.
  • Liu Y; National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agricultural, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, China.
  • Chen H; State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, Frontiers Science Center for Molecular Design Breeding, China Agricultural University, China.
  • Ji P; National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agricultural, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, China.
  • Wang B; National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agricultural, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, China.
  • Zhang R; State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, Frontiers Science Center for Molecular Design Breeding, China Agricultural University, China. Electronic address: zhangran0628@cau.edu.cn.
  • Liu G; National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agricultural, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, China. Electronic address: gshliu@cau.e
Pharmacol Res ; 206: 107290, 2024 Aug.
Article en En | MEDLINE | ID: mdl-38960012
ABSTRACT
The placenta, as a "transit station" between mother and fetus, has functions delivering nutrients, excreting metabolic wastes and secreting hormones. A healthy placenta is essential for fetal growth and development while the melatonergic system seems to play a critical physiological role in this organ since melatonin, its synthetic enzymes and receptors are present in the placenta. In current study, Mtnr1a and Mtnr1b knockout mice were constructed to explore the potential roles of melatonergic system played on the placental function and intrauterine growth retardation (IUGR). The result showed that Mtnr1a knockout had little effect on placental function while Mtnr1b knockout reduced placental efficiency and increased IUGR. Considering the extremely high incidence of IURG in sows, the pregnant sows were treated with melatonin. This treatment reduced the incidence of IUGR. All the evidence suggests that the intact melatonergic system in placenta is required for its function. Mechanistical studies uncovered that Mtnr1b knockout increased placental oxidative stress and apoptosis but reduced the angiogenesis. The RNA sequencing combined with histochemistry study identified the reduced angiogenesis and placental vascular density in Mtnr1b knockout mice. These alterations were mediated by the disrupted STAT3/VEGFR2/PI3K/AKT pathway, i.e., Mtnr1b knockout reduced the phosphorylation of STAT3 which is the promotor of VEGFR2. The downregulated VEGFR2 and its downstream elements of PI3K and AKT expressions, then, jeopardizes the angiogenesis and placental development.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Placenta / Transducción de Señal / Ratones Noqueados / Neovascularización Fisiológica / Receptor 2 de Factores de Crecimiento Endotelial Vascular / Factor A de Crecimiento Endotelial Vascular / Receptor de Melatonina MT2 / Retardo del Crecimiento Fetal / Melatonina Límite: Animals / Pregnancy Idioma: En Revista: Pharmacol Res Asunto de la revista: FARMACOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Placenta / Transducción de Señal / Ratones Noqueados / Neovascularización Fisiológica / Receptor 2 de Factores de Crecimiento Endotelial Vascular / Factor A de Crecimiento Endotelial Vascular / Receptor de Melatonina MT2 / Retardo del Crecimiento Fetal / Melatonina Límite: Animals / Pregnancy Idioma: En Revista: Pharmacol Res Asunto de la revista: FARMACOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos