title: Role of vascular endothelial growth factor in maintenance of pregnancy in mice.
abstract: It is well known that withdrawal of progesterone from the maternal circulation is a critical stimulus to parturition in rodents, such as rats and mice. However, mechanisms that determine the timing of progesterone withdrawal are not completely understood. In the present study, we examined whether the vascular endothelial growth factor (VEGF) system in the corpus luteum (CL) contributes to the regulation of circulating progesterone levels and acts as a determinant of the timing of parturition in mice. We found that reduction in the expression levels of VEGF and VEGF receptor-2 in the CL precedes the impairment of luteal circulation and a series of events leading to parturition (i.e., reduction of plasma progesterone, enhancement of myometrium contractility, and onset of parturition). Blocking of VEGF signaling by using the inhibitor of VEGFR tyrosine kinase KRN633 at mid-pregnancy caused a similar sequence of events and induced preterm birth. These results suggest that the VEGF system in the CL plays a critical role in maintaining a high level of circulating progesterone, and determining the timing of parturition in mice.
authors: Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors: Yoshiko
authors: Y
authors: Wada
authors: Hiromi
authors: H
authors: Ozaki
authors: Naomichi
authors: N
authors: Abe
authors: Asami
authors: A
authors: Mori
authors: Kenji
authors: K
authors: Sakamoto
authors: Tohru
authors: T
authors: Nagamitsu
authors: Tsutomu
authors: T
authors: Nakahara
authors: Kunio
authors: K
authors: Ishii
mesh_terms: D000818:Animals; D003338:Corpus Luteum / Q000502:physiology; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D036801:Parturition / Q000187:drug effects / Q000502:physiology*; D010671:Phenylurea Compounds / Q000494:pharmacology; D011247:Pregnancy; D011374:Progesterone / Q000097:blood* / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology; D040262:Receptors, Vascular Endothelial Growth Factor / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*
chemical_list: D010671:Phenylurea Compounds; D011799:Quinazolines; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D011374:Progesterone; C508488:N-(2-chloro-4-((6,7-dimethoxy-4-quinazolinyl)oxy)phenyl)-N'-propylurea; D040262:Receptors, Vascular Endothelial Growth Factor