Long chain polyunsaturated fatty acids and oxytocin signaling in pregnant human myometrial smooth muscle cells
Date
2009
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Abstract
Since the suggestion by Olsen and colleagues that the pattern of exceptionally high birth weight in the Faroe Islands is related to a high intake of seafood, a number of epidemiological studies and interventional clinical trials have explored the possibility that consumption of long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) abundant in fish and fish oil, such as 20:5 eicosapentaenoic acid (EPA) and 22:6 docosahexaenoic acid (DHA), may lengthen gestational duration. A dose response relation between dietary LC n-3 PUFA and gestational duration has emerged wherein expectant women who consume small amounts of fish stand to benefit the most from LC n-3 PUFA supplementation. The mechanisms are not well understood. Although prostaglandins (PG) of the 2-series are known to play a role in the initiation and progress of labor, an interpretation based on modulation of PG biosynthesis appears unlikely since idiopathic preterm labor is accompanied by low PG concentrations. Consequently, we investigated one potential PG-independent mechanism of LC n-3 PUFA action using a pregnant human myometrial smooth muscle cell line, PHM1-41, as a model. Our primary goal was to characterize the effect of DHA treatment on the signaling pathway of oxytocin, a potent uterotonic hormone involved in labor. The addition of 10 µM to 100 µM DHA to the culture media for 48 hrs resulted in incorporation and dose dependent enrichment of DHA in membrane lipid. DHA significantly inhibited IP3 elaboration (at 30 µM and 100 µM) and [Ca2+]i mobilization (at 100 µM) in response to oxytocin stimulation compared with bovine serum albumin (BSA) control and equimolar 18:1 oleic acid (OA). DHA at 30 µM and 100 µM significantly reduced receptor density in the membrane (Bmax) without altering the binding affinity (Kd) or rate of receptor internalization. These findings may be relevant to the reports of dietary fish and fish oil consumption prolonging gestation.
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Subject
myometrium
oxytocin
polyunsaturated fatty acids
smooth muscle cells
molecular biology
cellular biology
nutrition