Expression of angiogenic factors in the uteroplacental unit is altered at time of placentation in a porcine model of von Willebrand disease type 1 |
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| Affiliation: | 1. Werlhof Institute, Department of Fundamental and Clinical Research, Schillerstr. 23, 30159 Hannover, Germany;2. University of Veterinary Medicine Hannover Foundation, Institute for Anatomy, Bischofsholer Damm 15, 30173 Hannover, Germany;1. Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China;2. Key Laboratory of Birth Regulation and Control Technology of National Health and Family Planning Commission of China, Jinan, Shandong, China;3. Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China;4. National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong, China;5. The Key laboratory for Reproductive Endocrinology of Ministry of Education, Shandong, China;6. Maternal and Child Health Care of Shandong Province, Jinan, Shandong, China;1. National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, Beijing 100193, People’s Republic of China;2. College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu 225009, China;1. Institute of Biology, University of Brasília, Brasília, Brazil;2. Embrapa Genetic Resources and Biotechnology, Brasília, Brazil;3. Veterinary Medicine Department, University of Espírito Santo, Alegre, Brazil;1. Eutheria Foundation, Cross Plains, WI, 53528, USA;2. Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, 53706, USA;1. Department of Reproductive and Perinatal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu-shi, Shizuoka, 431-3192, Japan;2. Tawara IVF Clinic, 2-20, Izumi-cho, Suruga-ku Shizuoka-shi, Shizuoka, 422-8066, Japan;3. Department of Urology, Tesseikai Neurosurgery Hospital, Nakanohonmachi 28-7, Shijonawate, Osaka 575-8511, Japan;4. Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu-shi, Shizuoka, 431-3192, Japan;1. Universidad de Buenos Aires, Facultad de Medicina, Departamento de Biología Celular, Cátedra II de Histología, Buenos Aires, Argentina, CONICET-Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas (INBIOMED), Buenos Aires, Argentina;2. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y Diagnósticos (CEBBAD), Universidad Maimónides, Buenos Aires, Argentina;3. Centro de Estudios Farmacológicos y Botánicos (CEFYBO) CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina |
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| Abstract: | Von Willebrand disease (VWD) affects blood coagulation and correlates with angiodysplasia. Data on VWD-affected women point to slightly increased miscarriage rates. We aimed to investigate the impact of VWD on angiogenesis in the uteroplacental unit of pregnant pigs of a model of VWD type 1 (T1). Uteri, placentae, and embryos were harvested at time of placentation (day 29 to 31) from four sows (two wildtype (WT) and two heterozygous for a von Willebrand factor (VWF) mutation diagnosed with T1). T1 sows were bred to a T1 boar creating embryos of three different genotypes: WT, T1 or homozygous for the VWF mutation corresponding with VWD type 3 (T3). Uteroplacental tissues were examined histologically. Embryos were genotyped. Gene expression of angiogenic factors possibly related to VWF was determined by quantitative real-time PCR. Corresponding protein expression was analyzed by immunohistochemistry. Genotyping revealed 35.3% WT, 52.9% T1 and 5.9% T3 embryos (5.9% not classified confidently). No histological alterations were found. Gene expression of VEGF was significantly increased in T1 placentae while expression of ANG1, ANG2, TIE2, and ITGB3 was significantly reduced, confirmed on protein level for different cell types. TIE2/TIE1 ratios were significantly lower in T1 placentae. Distribution of embryo genotypes indicates selection favoring the WT. Significant expression differences of angiogenic factors in placentae suggest influence of VWF on these factors during placentation, although angiodysplasia was not observed. The alterations concerning VEGF/VEGFR-2 signaling, integrin expression and the ANG/TIE system may influence angiogenesis and vascular adaptation during placentation and thus the overall outcome of pregnancy. |
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| Keywords: | Angiogenic proteins Blood vessels Placenta Models Animal Sus scrofa |
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