Date of Award

1982

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Abstract

The objectives of the work described in this thesis were (1) to delineate major sites of prostanoid (PG) production in pregnant sheep by examining the concentrations of PG in intra-uterine tissues taken at different stages of pregnancy and correlating these with PG output from isolated cells prepared from these tissues and with PG concentrations in amniotic and allantoic fluids; (2) to correlate the effects of infusing ACTH to the fetal lamb and indomethacin to the mother on patterns of uterine activities and plasma steroid changes, with tissue steroid and PG concentrations and PG output in vitro; (3) to examine the effects of steroid and protein hormones on PG output in vitro; and (4) to examine the sequelae of fetal death, PG concentrations and uterine activity.;The principal findings were: (1) PG concentrations and output in vitro increased during the last third of pregnancy, and at this time highest PG concentrations were found in cotyledons and chorioallantois. (2) During ACTH-induced labour, concentrations of 6-oxo-PGF(,1(alpha)) were elevated in myometrium adjacent to the cervix, and PGF and PGE concentrations were higher at the tubal and cervical ends of the myometrium in all animals. Concentrations of PGE in endometrium and of PGF and 6-oxo-PGF(,1(alpha)) in cotyledons and chorioallantois were elevated during labour and were correlated with estrone concentrations in these tissues. Indomethacin, given to ACTH-treated animals reduced PG concentrations, the degree of cervical dilation and the frequency of uterine contractions. (3) The output of PGE in vitro from isolated caruncle cells prepared from ewes treated with estradiol-17(beta) in vivo was increased, and the output of all PG's examined were decreased following in vitro ovine placental lactogen (OPL) treatment. (4) The concentrations of all PGs were elevated in myometrium in sheep bearing fetuses which had died 12-26 h previously. The proportions of animals showing uterine activity however, were elevated only in sheep bearing fetuses which had died 34-72 h previously.;The results of this study suggest an association between PG's and uterine activity during labour and that estrogen and OPL may play a role in the regulation of uterine PG production.

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