Lysophosphatidic Acid (LPA) Signaling in Human and Ruminant Reproductive Tract
Figure 1
Schematic model illustrating the possible lysophosphatidic acid signaling in the bovine reproductive tract (LPA—lysophosphatidic acid; LPAR—lysophosphatidic acid receptor; PGFS—prostaglandin F2α synthase; PGES—prostaglandin E2 synthase; ATX—autotaxin; PLA2—phospholipase A2; FSH—follicle stimulating hormone; FSHR—follicle stimulating hormone receptor; E2—estradiol; CYP19A1—cytochrome P450 aromatase; 17βHSD—17β-hydroxysteroid dehydrogenase; TNF α—tumor necrosis factor α; TNFR1—tumor necrosis factor α receptor type 1; IFNγ—interferon γ; IFN—interferon ; Casp3—caspase 3; Fas/FasL—Fas antigen/Fas ligand; OAS1—2,5′-oligoadenylate synthase; ISG15—ubiquitin-like IFN-stimulated gene 15 kDa protein; StAR—StAR protein; P450 scc—cytochrome P450; 3βHSD—3β-hydroxysteroid dehydrogenase; PGF2α—prostaglandin F2α; PGE2—prostaglandin E2; and P4—progesterone). LPA derived from the blood plasma and produced in the uterus and ovary induces auto- and paracrine actions on the bovine endometrium, corpus luteum (CL), and the follicle. In the bovine endometrium LPA acting via LPAR1 induces PGE2 and inhibits PGF2α actions. In the ovarian follicle, LPA stimulates E2 production and FSH action in granulosa cells via increased expression of the FSHR and 17β-HSD. In the bovine CL, LPA stimulates P4 secretion through stimulation of 3βHSD. LPA augments IFN-dependent stimulation of ISG15 and OAS1 expression in the steroidogenic cells of the bovine CL. LPA suppresses TNFα and IFNγ, induced luteal cell apoptosis via inhibition of the stimulatory effect of the cytokines on the expression of Bax, Fas—FasL system, TNFR1, and Casp3 activity in the cultured steroidogenic luteal cells, which orientates the cells towards the survival state.
