Activity of platelet-activating factor acetylhydrolase in the mouse uterus during the estrous cycle, throughout the preimplantation phase of pregnancy, and throughout the luteal phase of pseudopregnancy

Abstract

Platelet-activating factor (PAF) is a potent autacoid produced by the embryo and the endometrium during early pregnancy. Its actions in vivo are dependent upon its half-life, which in turn is largely governed by its metabolism. PAF:acetylhydrolase is a major metabolic enzyme for PAF and is widespread in body tissues and fluids. This study was an examination of the activity of this enzyme in the uterus (uterine luminal fluids and endometrial scrapings) of mice in the periovulatory period, throughout the preimplantation phase of pregnancy, and throughout the luteal phase of pseudopregnancy PAF:acetylhydrolase activity was found in uterine washings and endometrial tissue; it was dependent upon incubation time and protein concentration and was destroyed by boiling. The activity was not affected by cations (Mg2+ and Ca2+) and was not inhibited by bromophenacyl bromide, a phospholipase A2 inhibitor. The specific and total activity changed dramatically throughout the reproductive cycle. Total tissue activity did not change significantly during the follicular phase. On the day after ovulation, tissue activity was lower in naturally mated mice and was maintained at this level until Day 4; there was no difference in this value between pregnant and pseudopregnant animals. On Days 5 and 6 of pseudopregnancy the total tissue activity increased, reaching a peak on Day 6 of 4609 pmol acetate released · min-1, approximately 780% higher than the value obtained on Day 4. Activity then decreased so that by Day 8 it was not different from preovulatory levels. For uterine luminal fluids, total activity significantly decreased during the follicular phase. This continued throughout the preimplantation phase with minimum activity being reached on Days 3 and 4 (7.68 pmol acetate · min-1 on Day 4 pseudopregnancy). There was no difference in activity between pregnant and pseudopregnant animals. Activity was slightly greater on Day 5 of pseudopregnancy and greatly increased thereafter to reach its maximum on Day 7, a value 5874% higher than that observed on Day 4. In ovariectomized animals, treatment with 2 mg progesterone/day for 3 days significantly suppressed PAF:acetylhydrolase activity in uterine fluids, while one day of treatment with 0.1-10 μg estradiol increased the activity. Thus, PAF:acetylhydrolase activity in the uterus decreased at the time when the embryo and endometrium are producing PAF; this would result in increased half-life and hence bioactivity of PAF in the uterus at this time. During the mid-luteal phase there was a substantial increase in the activity of PAF:acetylhydrolase, suggesting that during this time the half-life of any PAF produced in the uterus would be substantially reduced.