Cytokines and Angiogenesis in the Corpus Luteum

Abstract

In adults, physiological angiogenesis is a rare event, with few exceptions as the vasculogenesis needed for tissue growth and function in female reproductive organs. Particularly in the corpus luteum (CL), regulation of angiogenic process seems to be tightly controlled by opposite actions resultant from the balance between pro- and antiangiogenic factors. It is the extremely rapid sequence of events that determines the dramatic changes on vascular and nonvascular structures, qualifying the CL as a great model for angiogenesis studies. Using the mare CL as a model, reports on locally produced cytokines, such as tumor necrosis factor α (TNF), interferon gamma (IFNG), or Fas ligand (FASL), pointed out their role on angiogenic activity modulation throughout the luteal phase. Thus, the main purpose of this review is to highlight the interaction between immune, endothelial, and luteal steroidogenic cells, regarding vascular dynamics/changes during establishment and regression of the equine CL.

Fetal Sex‐Based Differences in Maternal Hormones, Angiogenic Factors, and Immune Mediators During Pregnancy and the Postpartum Period

“…An appropriate balance between proangiogenic and antiangiogenic factors is essential to develop adequate, but not pathologically aggressive, placental invasion. Adding an additional layer of complexity, many angiogenic factors have immune-modulating properties 24 ; therefore, we considered the role of angiogenesis proteins along with recognized immunoregulatory molecules. We found that angiogenic growth factors such as PlGF and VEGF-A were increased in the blood of women carrying a male fetus, where higher levels of inflammatory cytokines were observed.…”

“…Of the 38 women available for analysis, 19 carried a male fetus, and 19 carried a female fetus. The mean age of the cohort of 38 women was 28.2 years (range [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34]. There were no significant differences in age between women carrying male fetuses versus female fetuses (average 27.7 versus 28.7 years, respectively; P = 0.434).…”

Color Doppler provides a reliable and rapid means of monitoring luteolysis in female donkeys

“…In mares, an increase in cortisol has been observed after the administration of a single bolus of PGF2a [42]. Thus, although more studies are needed, luteolysis should be understood as a physiological process of inflammation involving a release of prostaglandins, other hormones, and cytokines, which results in ischemia-induced necrosis of the luteal tissue [14]. As described in the cow, an increase in luteal blood flow may be triggered by vasodilatory prostaglandin I2 or prostacyclin and nitrogen oxide release from arterioles surrounding the CL; this probably also causes vasodilatation in the active CL jenny after induced luteolysis.…”

“…Luteal vascularization plays an important role in the physiology of the CL [14]. Intense angiogenesis occurs during luteinization in many species [15][16][17], but curiously, in the cow, increased luteal vascularization also occurs before an intense reduction of the same just before luteolysis [18,19].…”

The role of cytokines in immune regulation of female reproductive physiology

“…The immune system contribute to the transient nature of the CL (development, maintenance and regression), for example, with regulation of leukocytes in the ovary and secretion of regulatory cytokines. T cells, macrophages, eosinophils, and neutrophils produce and secrete interleukins, prostaglandins, interferon γ (IFN-γ), TNF-α, and angiogenic factors such as vascular endothelial growth factor A (VEGF-A) and fibroblast growth factor 2 (FGF2) (Reynolds et al, 1994;Shirasuma et al, 2012;Galvão et al, 2013). Therefore, during luteolysis, there is a significant increase in the number of these cells in the CL, with luteal cell apoptosis and subsequent phagocytosis of the debris; these events characterize the luteolytic cascade as an immune and inflammatory-like response.…”