Existence of the Lymphatic System in the Primate Corpus Luteum.

Abstract

To date, there have been no detailed studies on the lymphatic system in the primate corpus luteum (CL); early reports suggested that the presence of this ''secondary circulation'' in luteal tissue is species-dependant. Therefore, studies were designed to determine if (a) lymphatic vessels exist, and (b) recently discovered lymphangiogenic factors and their receptor are expressed in the macaque CL during the menstrual cycle. Immunohistochemistry (IHC) detected the lymphatic endothelial cell marker, lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1), in some endothelial cells and vessels within the ovarian stroma and theca layer of preovulatory follicles and in the CL. Dual fluorescent IHC demonstrated that LYVE1 co-localized with another lymphatic endothelial cell marker D2-40, but a blood vascular endothelial cell marker (von Willebrand Factor, VWF) was in different cells. The numbers and staining intensity of LYVE1-positive cells in the CL appeared to increase from early to mid luteal phase, and remained elevated thereafter. RT-PCR detected cDNA fragments for mRNAs encoding VEGFC, FIGF, and their receptor FLT4 in CL. Real-time PCR analyses revealed similar patterns of VEGFC and FLT4 expression during the luteal lifespan; mRNA levels increased (p < 0.05) from early to mid luteal phase and decreased (p < 0.05) by late luteal phase. In contrast, FIGF levels were elevated initially, declined (p < 0.05) at mid luteal phase, and then increased (p < 0.05) to very late luteal phase. The data strongly suggest that lymphatic vessels are present in the primate CL, and that the VEGFC=FIGF-FLT4 system regulates lymphangiogenesis and luteal structure-function during the menstrual cycle.

Lymphangiogenesis and Inflammation—Looking for the “Missing Pieces” of the Puzzle

“…Inflammatory lymphangiogenesis was also reported during physiologic processes, and the best example can be considered immune cell-induced angiogenesis and lymphangiogenesis inside corpus luteum (Xu and Stouffer 2009). Gradual loss of progesterone production during ovarian cycle induces recruitment of inflammatory cells, mainly lymphocytes and macrophages which invade human corpus luteum (Best et al 1996;Hameed et al 1995;Takaya et al 1997).…”

“…Gradual loss of progesterone production during ovarian cycle induces recruitment of inflammatory cells, mainly lymphocytes and macrophages which invade human corpus luteum (Best et al 1996;Hameed et al 1995;Takaya et al 1997). First, lymphatic vessels were initially detected at the periphery of regressing corpus luteum (Xu and Stouffer 2009) and later inside it. This observations suggest lymphatic vessel recruitment from preexisting vessels surrounding corpus luteum, but this Fig.…”

Expression of Lymphangiogenic Vascular Endothelial Growth Factor Family Members in Bovine Corpus Luteum

“…The existence of a lymphatic system in CL of primates has been suggested recently (Xu and Stouffer, ). We could now demonstrate that in bovine CL, the lymphangiogenic factors VEGFC, VEGFD and FLT4 are also detectable at both mRNA and protein levels.…”

“…VEGFC mRNA occurs in certain tumour cell lines, but also at low levels in many tissues, most prominently in the heart, placenta, skeletal muscle, small intestine and ovary (Enholm et al., ). Xu and Stouffer () recently proved the existence of the lymphatic system in the primate CL by immunohistochemistry (IHC), dual fluorescent IHC and real‐time RT‐qPCR analyses of known lymphangiogenic factors. PCR analyses revealed similar patterns of VEGFC and FLT4 expressions during the luteal lifespan; mRNA levels increased from early to mid‐luteal phase and decreased by late luteal phase.…”

Immune and vascular contributions to organogenesis of the testis and ovary

“…Adult ovaries develop a rich lymphatic network, mainly located in the medulla and in the theca layer of developing follicles [114]. In addition, lymphatic vessels are also abundant in the corpora lutea of mice, rats, and primates [115][116][117].…”