Lysophosphatidic acid stimulates rat uterine contraction <i>in vitro</i>

Abstract

Lysophosphatidic acid (LPA) has been implicated in the uterine endometrial functions of implantation and decidualization; however, not much is known about its myometrial contractile function. Herein we characterized the uterotonic effects of LPA in non-pregnant (estrus) and periparturient rats in vitro. LPA dose-dependently (0.01-10 µM) stimulated the amplitude and integral, but not the frequency, of the uterine strip contraction of estrous rats. The stimulatory effect of LPA was enhanced 1 day before parturition but was lost 1 day postpartum. LPA did not cause the de novo synthesis of prostaglandin (PG) F2α but stimulated contractions cooperatively with the PG. LPA-induced contractions were significantly inhibited by an LPA1/2/3 antagonist in the uteri of estrous rats but not in term rats. In this study we characterized the uterotonic effect of a natural LPA that occurs at physiological concentrations, changes with reproductive states, and is independent of mediation by the newly synthesized PG.

Expression of lysophosphatidic acid receptors in the rat uterus: cellular distribution of protein and gestation-associated changes in gene expression

“…2B and 2C ). In the myometrium at term that possess robust contracting activity both in spontaneous and LPA-stimulated conditions [ 19 ], the immunoreactivities for LPA3, LPA6, and LPA4 were positive, and in any subtypes the immunoreactivity was more intense in the outer muscular layer than in the inner one ( Fig. 2B and 2C ).…”

“…Given with their established potencies of increasing Ca 2+ mobilization and Rho activation [ 7 , 33 , 37 ] and evidence for those in LPA-treated muscle cells in vitro [ 8 , 20 ], significant co-existence in outer muscle layers of LPA3, LPA4, and LPA6 indicates their possible contribution to contractile function in response to LPA. Our recent functional study revealed that Ki16425, an LPA1/2/3 antagonist, significantly inhibited LPA-stimulated uterine contraction in vitro in rats of estrus but not at term [ 19 ]. It is therefore suggested that uterine myometrium co-expresses multiple subtype for LPA-stimulated contraction that alters dependently on physiological states.…”

“…Marked immunoreactions for LPA3 and LPA4 were present in stromal cells especially beneath the endometrial epithelium (Figure 2B and 2C). In the myometrium at term that possess robust contracting activity both in spontaneous and LPA-stimulated conditions [19], the immunoreactivities for LPA3, LPA6, and LPA4 were positive, and in any subtypes the immunoreactivity was more intense in the outer muscular layer than in the inner one (Figure 2B and 2C). Smooth muscle cells in stromal arteriole were also positive.…”

“…Lysophosphatidic acid (LPA) has multiple roles in mammalian reproductive physiology and pathology [ 18 , 32 , 33 ]. LPA actions reported to date in uteri of rodent, ruminant, and other species include myometrial contraction [ 11 , 16 , 19 , 29 ], implantation [ 11 , 24 , 34 , 35 ], decidualization [ 2 , 3 , 24 ], and stromal cell proliferation [ 1 ] and prostaglandin (PG) production [ 3 , 9 , 15 , 22 , 30 , 31 ]. A total of six kinds of G protein-coupled receptors, LPA1-6, exist to mediate effects of this lipid mediator in the body [ 7 , 33 , 37 ].…”

Imaging the dynamics of uterine contractions in early pregnancy

“…In vitro mechanical transducer-induced assays suggested that while control uteri can respond to LPA-LPAR3 agonist, Lpar3 -/- uteri fail to respond to the agonist as measured by contractility however these uteri contract in the presence of acetyl choline (Hama et al, 2007). Further, LPA can dose dependently increase contraction amplitude in estrus stage rat uteri in in vitro uterine strips and in vivo (Nagashima et al, 2023; Tokumura et al, 1980). Additionally, a study with gilts (pig uteri) suggested that LPA signaling enhances contractility in early pregnancy uteri but not non-pregnant uteri (Markiewicz et al, 2012).…”