Significance of mast cells in spermatogenesis, implantation, pregnancy, and abortion: Cross talk and molecular mechanisms

Abstract

Both subsets of MCs including MCTC (tryptase‐positive, chymase‐positive) and MCT (tryptase‐positive, chymase‐negative) are present in the testis and epididymis. Increased number of MCs, higher levels of MC‐released tryptase in testis and seminal plasma of males with fertility problems, and promoting sperm motility in individuals with oligozoospermia after using MC blockers provide evidence that MCs may play a role in male infertility/subfertility disturbances. MC‐released tryptase and histamine contribute to the fibrosis and may disrupt spermatogenesis. MCs not only influence the process of spermatogenesis but also have effects on the function of other testis‐residing cells. MC‐derived histamine may influence the steroidogenesis of Leydig cells by acting through H1R and H2R receptors. Additionally, the interaction between MC‐released ATP and P2X receptors expressed on the peritubular cells may induce the production of the pro‐inflammatory mediators by peritubular cells. Further investigations showed that MCs may be involved in the pathology of female infertility during implantation, pregnancy, and abortion. In the uterus, MCT subtype is abundant in myometrium and adjacent basal layer while MCTC subtype is distributed in all layers. MCs in response to hormones mainly estradiol and progesterone become activated and release a wide range of mediators including histamine, VEGF, proteases, and metalloproteinases (MMPs) that have a role in different stages of pregnancy. An increasing influx of MCs to the cervix during the pregnancy occurs that helps to the physiologic cervical ripening. While MMPs degrade the extracellular matrix (ECM), VEGF modulates neovascularization and histamine influences the embryo implantation. MC‐derived histamine may have a positive effect during implantation due to its participation in tissue remodeling. MC proteases including tryptase and chymase activate the precursors of MMP2 and MMP9 to mediate ECM degradation during the physiologic menstrual cycle. There is a line of evidence that MCs have a role in abortion by releasing TNF‐α.

Downregulating testosterone levels enhance immunotherapy efficiency

“…In addition, the expression of PD-L1 on both CD45 + and CD45 − subpopulations is significantly downregulated in the anti-PD-L1 groups, hinting possible disruption of the inherent immunosuppressive circumstances ( Figure 4c ). Considering that IgG antibodies can trigger the activation of the mast cells and the resultant histamine release may affect the steroidogenesis in Leydig cells, 27 , 28 both the infiltration of mast cells in the testes and the histamine levels in the blood was analyzed. As shown in Figure 4d , there is no substantial difference in the infiltration of mast cells after treatment with anti-PD-L1, while the blood histamine levels in the anti-PD-L1 group are significantly reduced.…”

Mast Cells in the Mammalian Testis and Epididymis—Animal Models and Detection Methods

“…Available data regarding MCs in the testis abounds exquisite reviews on humans [16,33,130] and a comprehensive review on MCs in the nonmammalian vertebrates [42], including the presence of MCs in the testes of birds, frogs, and lizards. A comprehensive review on the mammalian testicular and epididymal MC has not been found written from the perspective of method and result comparison in the available literature and may have a significant impact in drawing the attention of future authors to crucial problems in MC analysis.…”

Proteomic Analysis of Differentially Expressed Proteins in the Placenta of Anticardiolipin Antibody‐ (ACA‐) Positive Pregnant Mice after Anzi Heji Treatment

“…ACA induces abortion via promoting thrombosis, damaging trophoblasts, and activating inflammation and the complement response by targeting β 2-GPI [ 14 , 15 ]. TNF- α plays a critical role in the physiology and pathology of pregnancies by regulating the immune balance at the maternal-fetal interface [ 16 , 17 ]. Excessive TNF- α causes thrombosis and TNF- α can activate immunocompetent cells in the decidual stroma, induce immune-mediated destruction and immune rejection, hinder the maintenance of pregnancy and embryo implantation, disrupt the homeostasis of the maternal uterine environment, and cause spontaneous abortion [ 16 , 18 , 19 ].…”