Review Article Impact of angiogenic and innate immune systems on the corpus luteum function during its formation and maintenance in ruminants § Akio Miyamoto a, *, Koumei Shirasuna b , Takashi Shimizu a , Motozumi Matsui c a Graduate School of Animal and Food Hygiene, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Japan b Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi 349-0498, Japan c Department of Clinical Veterinary Science, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Japan r e p r o d u c t i v e b i o l o g y 1 3 ( 2 0 1 3 ) 2 7 2 – 2 7 8 a r t i c l e i n f o Article history: Received 21 August 2013 Accepted 28 September 2013 Keywords: Corpus luteum development Angiogenesis Lymphangiogenesis PMN Innate immune system Early pregnancy a b s t r a c t The corpus luteum (CL) is formed from an ovulated follicle, and grows rapidly to secrete progesterone (P4) thereby supporting implantation and maintenance of pregnancy. It is now evident that angiogenesis is necessary to form the structure of the developing CL as well as to acquire the steroidogenic capacity to secrete large amounts of P4. It is of interest that the increases in CL size, plasma P4 concentration and luteal blood flow are occurring in parallel during the first seven days after ovulation. Angiogenic factors, such as vascular endothelial growth factor-A (VEFGA) and basic fibroblast growth factor (FGF2), play a central role in promoting cell proliferation and angiogenesis in the developing CL. Angiopoietins regulate the stability of blood vessels, which directly affects angiogenesis or angiolysis via angiogenic factors. Vasohibin-1 is a novel negative feedback regulator, which inhibits VEGF-based vasculogenesis. It became evident that the immune cells, i.e., macrophages, eosinophils and neutrophils are recruited into the CL – using the innate immune system – just after ovulation which is accompanied by bleeding. The immune cells support active angiogenesis and thus the growth of the CL. In cows, the lymphatic system, but not blood vascular system, is reconstituted during early pregnancy, and embryonic trophoblast-derived interferon tau could play a crucial role in inducing lymphangiogenesis. This novel phenomenon may support a maternal recognition of pregnancy in shifting the local systems in such a way that they ensure a long-term supply of P4 over the period of pregnancy. Overall, the current findings support the concept that several major components involved in the regulation of the CL development and maintenance overlap in stimulating steroidogenesis, angiogenesis, vascular function and the innate immune system. # 2013 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved. § The material described in this review article was presented as an invited lecture at Ludwig Fraenkel Symposium ‘‘Endocrine Control of Corpus Luteum Function’’ in Wroclaw, Poland (5–6 September, 2013). * Corresponding author. Tel.: +81 155 49 5416; fax: +81 155 49 5593. E-mail address: akiomiya@obihiro.ac.jp (A. Miyamoto). Available online at www.sciencedirect.com ScienceDirect journal homepage: http://www.elsevier.com/locate/repbio 1642-431X/$ – see front matter # 2013 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved. http://dx.doi.org/10.1016/j.repbio.2013.09.006