HUMAN FETAL MEMBRANE CONTRIBUTION TO THE PREVENTION OF PARTURITION - UTEROTONIN DEGRADATION

This investigation was conducted to evaluate the potential capacity of the human fetal membranes-decidua parietalis, and in particular the c horion laeve, to degrade uterotonins that are produced in amnion, are present in amniotic fluid, or both. The four uterotonins that have bee n evaluated most frequently as myometrial contractants potentially inv olved in the initiation of human parturition are prostaglandins, oxyto cin, endothelin-1, and platelet-activating factor. We assessed the lev els of mRNA and the specific activities (SAs) of enkephalinase (the pl asma membrane endopeptidase that degrades endothelins) and prostagland in dehydrogenase (PGDH) in human fetal membranes, i.e. amnion and chor ion laeve, and in decidua parietalis. The SA of oxytocinase (which ina ctivates oxytocin) in these tissues also was determined. The SA of enk ephalinase in chorion laeve from all anatomical sites (singleton and d iamnionic-dichorionic twin placentae) in all pregnancies studied (mean +/- SEM, 95 +/- 7.9 ng/min.mg protein; n = 28) is similar to that in human fetal kidney (89.5 +/- 2.8; n = 6). Kidney tissue is believed to be one of the richest sources of enkephalinase. The SAs of enkephalin ase in amnion (18.3 +/- 2.3 nmol/min.mg protein; n = 29) and in decidu a parietalis (31.8 +/- 6.7; n = 20) also were high, but significantly less than that in chorion laeve. The level of enkephalinase mRNA in ch orion laeve in singleton pregnancies is high, as is the SA of enkephal inase (111.9 +/- 10.6 nmol/min.mg protein; n = 17). In paired chorion laeve tissues from five diamnionic-dichorionic twin placentae, the SAs of enkephalinase in reflected chorion laeve (74 +/- 12.8; P < 0.06 co mpared with singletons) and fused chorion laeve (64.8 +/- 6.5; P < 0.0 01 compared with singletons) were similar. The SA of PGDH in reflected chorion laeve (46.3 +/- 6.9 nmol/min.mg protein; n = 19) was signific antly greater than that in decidua (16 +/- 5.5; n = 15). There was a s ignificant correlation between the levels of PGDH mRNA and PGDH enzyme SA. In fused chorion laeve of diamnionic-dichorionic twin placentae, the SA of PGDH (14.9 +/- 7.3; n = 4) was much less than that in reflec ted chorion laeve of the same twin pregnancy (70.5 +/- 14.7; n = 4). P GDH mRNA was not detectable in amnion tissue (n = 5) by northern analy sis, and the SA of PGDH (<1.2 +/- 1.0; n = 6) in amnion was undetectab le or near the lower limit of assay detection. The SA of oxytocinase i n chorion laeve (6.9 +/- 0.4 nmol/min.mg protein; n = 14) was very hig h and somewhat greater than that in amnion (3.5 +/- 0.9; n = 5) and de cidua (4.2 +/- 0.4; n = 5). The SAs of enkephalinase, PGDH, and oxytoc inase in chorion laeve tissues obtained before the onset of labor were not significantly different from those in chorion laeve tissues obtai ned after labor began.