Ceptor3. MALE REPRODUCTIVE SYSTEM19. THE IMMUNOPHYSIOLOGY OF MALE REPRODUCTIONFIGURE 19.12 Synthesis of bioactive lipids. Cleavage ofmembrane-bound phospholipids by the action of phospholipase A2 leads to production of arachidonic acid and lysophospholipids, including the lysophosphatidylcholines. Arachidonic acid may possibly be converted to prostaglandins, prostacyclins or thromboxanes through the intermediates prostaglandin G and H by the action on the rate-limiting prostaglandin-endoperoxide synthase (PTGS) enzymes. Alternatively, lipoxygenases may catalyze the conversion of arachidonic acid to leukotrienes or lipoxins. The majority of the goods in these complex pathways have certain regulatory activities, like profound effects on immune responses plus the vasculature.interactions, or through metabolism to other active immunoregulatory metabolites, for instance the immunosuppressive ligand for peroxisome proliferator-activated receptor- (PPAR), 15deoxy-PGJ2.609,610 An option synthetic pathway, catalyzed by the lipoxygenases, converts arachidonic acid for the closely-related leukotrienes and lipoxins, which likewise possess diverse metabolic, vascular, and inflammation-regulating activities.178,611 The enzymes responsible for prostanoid biosynthesis are expressed throughout the male reproductive tract.612615 Most testicular cells express both forms of PTGS and possess the capacity to generate prostaglandins in vitro,615 while there are actually considerable cell type-specific and species-specific differences in the relative levels of expression.61618 Within the normal rat testis, PTGS2 is responsible for the majority of prostaglandin production, and chronic therapy having a specific PTGS2 inhibitor, celecoxib, considerably reduces intratesticular PGE2 levels.615,619 Alternatively, intratesticular PGE2 levels are barely impacted by acute LPS therapy.615 This may possibly be resulting from the fact that macrophages inside the rat testis express PTGS2 at extremely low levels, relative to other testicular cells, however they are the only testis cell variety to respond to an inflammatory stimulus with a substantial improve in PTGS2 activity.615 These information indicate a maintenance part for the so-called inducible PTGS2 enzyme in testicular function. Prostaglandins, especially PGE2 and PGF2, are clearly implicated within the handle of IL-13 Formulation Leydig cell improvement inthe immature testis, production of pro-inflammatory cytokines by the Leydig cell, autoregulation of steroidogenesis inside the adult, and the decline in Leydig cell function that occurs for the duration of aging.401,620,621 Even so, the actual value of prostanoids in regulating testicular function remains uncertain: male mice lacking either PTGS2 or PTGS1 are regarded as to be fertile,622 and research around the effects of prostaglandins or different PTGS inhibitors on Gutathione S-transferase Inhibitor custom synthesis spermatogenesis and fertility have made conflicting outcomes.618,619,623,624 Solutions of the lipoxygenase pathway, most notably LTB4, have already been implicated within the regulation of Leydig cell steroidogenesis by LH.625,626 Moreover, production of PGE2 and PGF2 induced by PTGS2 mediates the effects of IL1 on protein and lipid regulation by the Sertoli cell involved in supporting spermatogenesis and inflammation within the testis.424,425 A partnership among expression levels of IL1 and PTGS2 in the testes of infertile men also has been reported.627 These observations suggest that PTGS2 and prostanoid production mediate at the least a few of the effects of inflammation on testicular function.Oxidative.