Emerging roles of immune cells in luteal angiogenesis
Koumei Shirasuna A C , Takashi Shimizu A , Motozumi Matsui B and Akio Miyamoto A D
+ Author Affiliations
- Author Affiliations
A Graduate School of Animal and Food Hygiene, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555, Japan.
B Department of Clinical Veterinary Science, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555, Japan.
C Present address: Division of Bioimaging Sciences, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi 349-0498, Japan.
D Corresponding author. Email: akiomiya@obihiro.ac.jp
Reproduction, Fertility and Development 25(2) 351-361 https://doi.org/10.1071/RD12096
Submitted: 24 February 2012 Accepted: 1 August 2012 Published: 31 August 2012
Abstract
In the mammalian ovary, the corpus luteum (CL) is a unique transient endocrine organ displaying rapid angiogenesis and time-dependent accumulation of immune cells. The CL closely resembles ‘transitory tumours’, and the rate of luteal growth equals that of the fastest growing tumours. Recently, attention has focused on multiple roles of immune cells in luteal function, not only in luteolysis (CL disruption by immune responses involving T lymphocytes and macrophages), but also in CL development (CL remodelling by different immune responses involving neutrophils and macrophages). Neutrophils and macrophages regulate angiogenesis, lymphangiogenesis, and steroidogenesis by releasing cytokines in the CL. In addition, functional polarisation of neutrophils (proinflammatory N1 vs anti-inflammatory N2) and macrophages (proinflammatory M1 vs anti-inflammatory M2) has been demonstrated. This new concept concurs with the phenomenon of immune function within the luteal microenvironment: active development of the CL infiltrating anti-inflammatory N2 and M2 versus luteal regression together with proinflammatory N1 and M1. Conversely, excessive angiogenic factors and leucocyte infiltration result in indefinite disordered tumour development. However, the negative feedback regulator vasohibin-1 in the CL prevents excessive tumour-like vasculogenesis, suggesting that CL development has well coordinated time-dependent mechanisms. In this review, we discuss the physiological roles of immune cells involved in innate immunity (e.g. neutrophils and macrophages) in the local regulation of CL development with a primary focus on the cow.
Additional keywords: corpus luteum development, lymphangiogenesis, macrophages, neutrophils.
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