The Interface of the Immune and Reproductive Systems in the Ovary: Lessons Learned from the Corpus Luteum of Domestic Animal Models

Abstract

Citation Pate JL, Toyokawa K, Walusimbi S, Brzezicka E. The interface of the immune and reproductive systems in the ovary: lessons learned from the corpus luteum of domestic animal models. Am J Reprod Immunol 2010 The dynamic changes that characterize the female reproductive system are regulated by hormones. However, local cell‐to‐cell interactions may mediate responsiveness of tissues to hormonal signals. The corpus luteum (CL) is an excellent model for understanding how immune cells are recruited into tissues and the role played by those cells in regulating tissue homeostasis or demise. Leukocytes are recruited into the CL throughout its lifespan, and leukocyte‐derived cytokines have been found in corpora lutea of all species examined. The proinflammatory cytokines inhibit gonadotropin‐stimulated steroidogenesis, profoundly stimulate prostaglandin synthesis by luteal cells, and promote apoptosis. However, there is mounting evidence that leukocytes and luteal cells communicate in different ways to maintain homeostasis within the functional CL. Domestic animals have provided important information regarding the presence and role of immune cells in the CL.

It Takes Two to Tango but Four for the Finale

“…The most compelling differences between CL that regressed and those that did not were changes in mRNAs consistent with the concept of autoamplification of luteal prostaglandin synthesis and in immune response genes. This study by Atli et al [3] supports the notion that luteal prostaglandin synthesis is an obligate component of the luteolytic process, first suggested by Milvae [27] and further defined by Silva et al [28] and Niswender et al [29], and it adds to the growing amount of evidence that immune cells within the CL mediate some of the luteolytic effects of PGF 2a [18,30]. Most importantly, this work clearly demonstrates that the process of luteolysis involves multiple pathways and their repeated activation to commit the cells to a pathway that will lead to regression.…”

Dynamics of Immune Cell Types Within the Macaque Corpus Luteum During the Menstrual Cycle: Role of Progesterone1

“…Because NK cells appear to promote placentation and uterine vascular remodeling [44], they may have a similar role in promoting vessel growth, maturation and stability during formation (early) and function (mid-to mid-late) of the CL, before assuming degenerative roles during luteal regression. NK cells may be considered the innate counterparts of cytotoxic T cells [4], and may switch from trophic to lytic roles during the lifespan of primate CL much as proposed for T cells in the CL of domestic animals [2,50]. The dual functions of both NK and T-cells contribute to the overlap in cells participating in innate and adaptive immune responses [4], and thus further investigation into cytokine/chemokine production by ovarian NK cells are warranted.…”

“…Studies by several investigators using domestic animal species support a role for immune cells in regulating the functional lifespan of the corpus luteum (CL) [2]. During luteal regression, macrophages, monocytes, neutrophils, and T-lymphocytes increase in number in ruminant CL [5].…”

“…The events leading to luteal insensitivity to LH and subsequent functional and structural regression near the end of the menstrual cycle are poorly understood in primates. However, luteolysis in some species appears to be mediated, at least in part, by cells of the immune system [2]. Immune processes are classically considered to follow two main pathways; innate and adaptive responses [3].…”

Administration of the nonsteroidal anti-inflammatory drug tolfenamic acid at embryo transfer improves maintenance of pregnancy and embryo survival in recipient mice

“…There is a growing list of potential factors that may be involved in the luteolytic process, including endothelialderived proteins, immune cell-derived cytokines, reactive oxygen species, neuropeptides and lipophilic molecules. Bidirectional communication between luteal and immune cells may thus facilitate hormonally regulated survival and demise of the CL [7,26]. Both tolfenamic acid and flunixin meglumine could inhibit luteolysis by blocking PG synthesis but tolfenamic acid could also have effects over the immune responses and the survival of CL.…”