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Gestation Age-Related Increase in 50-kDa Rat Uterine Calcium-Independent Phospholipase A2 Expression Influences Uterine Sensitivity to Polychlorinated Biphenyl Stimulation¹

Department of Environmental Health Sciences,³ University of Michigan, Ann Arbor, Michigan 48109 Department of Pathobiology,⁴ University of Tennessee, Knoxville, Tennessee 37996

ABSTRACT

Phospholipase A2 (PLA2) enzymes catalyze the rate-limiting step in eicosanoid production by liberating arachidonic acid from membrane phospholipids. There is limited information regarding the expression pattern and activity of uterine PLA2 enzymes during pregnancy. Polychlorinated biphenyls (PCBs) are a group of persistent environmental toxicants previously associated with decreased gestation length that are capable of activating PLA2. The purpose of the present study was to determine whether uterine sensitivity to PCB stimulation is dependent on PLA2 expression, comparing rat uterine PLA2 expression in Gestational Day (gd) 10 versus gd20. Western blot analysis revealed a significant increase in the expression of calcium-dependent PLA2G2A and a 50-kDa protein immunoreactive to calcium-independent PLA2G6 antibody in gd20 compared to gd10 rat uterine tissue. The increased expression of the 50-kDa PLA2G6 was associated with a gestational age-related increase in endometrial calcium-independent PLA2 activity that was sensitive to inhibition by bromoenol lactone (P < 0.05). Longitudinal uterine strips isolated from gd10 or gd20 rat were suspended in muscle baths to evaluate uterine contractions following exposure to the ortho substituted congener PCB 50. Exposure to 50 and 100 µM PCB 50 significantly increased the frequency of gd20, but not gd10, uteri compared to solvent (dimethyl sulfoxide) controls (P < 0.05). Pharmacologic inhibition of PLA2G6, but not PLA2G2A, attenuated PCB-induced stimulation of gd20 uterine contractions (P < 0.05). These data suggest that PCB 50 stimulates uterine contractions by activating endometrial PLA2G6. Furthermore, gestation age-related sensitivity to PCB is associated with an increase in the expression of a previously unidentified 50-kDa PLA2G6 in rat uterus.

pregnancy, toxicology, uterus

¹ Supported by grants from the National Institute of Environmental Health Sciences (NIEHS), NIH, to R.L.C. (P42 ES04911) and by an Institutional Training Grant (T32-ES07062) to K.B. Portions of this research were presented at the 36th annual meeting of the Society for the Study of Reproduction, 19–22 July 2003, Cincinnati, Ohio.

² Correspondence: Kelly Brant, Department of Environmental Health Sciences, University of Michigan, 1420 Washington Heights, Ann Arbor, MI 48109-2029. FAX: 734 763 8095; kbrant{at}umich.edu

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