Mechanisms of paracrine regulation by fetal membranes of human uterine quiescence.
OBJECTIVE
To test the hypothesis that fetal membranes (chorion or amnion) release one or more factors responsible for myometrial quiescence.


METHODS
Myometrial samples were excised from women at elective term cesarean delivery prior to the onset of labor. Fetal membranes were obtained after cesarean delivery either before or during labor, and either term (greater than 37 weeks) or preterm (less than or equal to 36 weeks). Myometrial strips were placed in organ baths and contractions stimulated by oxytocin (10(-8) M). Contractility was measured under isometric conditions before and after exposure to fetal membranes or conditioned medium. The impact of either membrane or conditioned media on contractility was determined before and after myometrial K+ channel blockade.


RESULTS
Both chorion and amnion and their respective conditioned mediums decrease oxytocin-stimulated myometrial contraction. The inhibitory effect was greatest with membranes from preterm pregnancies (mean gestation 32 weeks, P <.05). The inhibitory effect was detectable in the presence of term labor, but was absent when the fetal membranes were obtained after preterm labor. Iberiotoxin, an inhibitor of large conductance Ca2+-activated K+ channels (BK(Ca)) reduced the effect of fetal membranes by 50% (P <.05).


CONCLUSIONS
We conclude that human fetal membranes release one or more factors that inhibit oxytocin-induced myometrial contractility. We suggest this factor (or factors) acts mainly by opening myometrial BK(Ca). The findings further support our hypothesis that the fetal membranes release a factor (or factors) that is central to myometrial quiescence and its premature loss leads to preterm delivery.
Carvajal
Jorge A
JA
Departmento de Obstetricia y Ginecología, Unidad de Medicina Materno Fetal, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile. jcarva@med.puc.cl
Vidal
Rossana J
RJ
Cuello
Mauricio A
MA
Poblete
Jose A
JA
Weiner
Carl P
CP
D000650:Amnion / Q000378:metabolism*; D002585:Cesarean Section; D002823:Chorion / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D005260:Female; D005865:Gestational Age; D006801:Humans; D007743:Labor, Obstetric; D010121:Oxytocin / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects; D011247:Pregnancy; D046509:Tissue Culture Techniques; D014590:Uterine Contraction / Q000187:drug effects*; D014599:Uterus / Q000187:drug effects* / Q000502:physiology*
D017077:Culture Media, Conditioned; D010455:Peptides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D010121:Oxytocin; C064719:iberiotoxin