The expression of prostanoid receptor genes in uterine and fetal tissues. Studies in the maternal and fetal baboon and the fetal and neonatal lamb

Smith, Gordon C.S. (2000) The expression of prostanoid receptor genes in uterine and fetal tissues. Studies in the maternal and fetal baboon and the fetal and neonatal lamb. PhD thesis, University of Glasgow.

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Abstract

1. The aim of this project was to determine whether advancing gestational age and parturition were associated with alteration in the relative level of expression of genes encoding prostanoid receptors in key uterine and fetal tissues. I also sought to determine whether advancing gestational age and parturition were associated with alteration in the expression of genes encoding lipoxygenase (LOX) enzymes in key intra-uterine tissues. 2. Caesarean hysterectomy was performed on 15 pregnant baboons in the last third of pregnancy. Samples of myometrium (from multiple uterine sites), cervix, decidua and chorion were obtained. In addition, the ductus arteriosus was obtained from nine fetal baboons, 28 fetal lambs and 4 neonatal lambs. Expression of genes was studied using Northern blot analysis and in situ hybridization. Expression of genes was quantified by Northern analysis as a ratio of the signal for the gene of interest to each of three housekeeping genes (glyceraldehyde-3-phosphate dehydrogenase [GAPDH], beta-actin and cyclophilin). Statistical comparison of the effects of gestational age and labour was performed using linear regression. Student's t-test, repeated measures analysis of variance and analysis of covariance, as appropriate. 3 Initial studies of animals not in labour using cDNA probes demonstrated transcripts of similar size to the human genes for prostanoid EP2, EP3, EP4, and FP receptor mRNA using Northern blot in myometrium. Myometrium from the lower uterine segment (LUS) had greater expression of EP2 receptor mRNA and less expression of EP3 mRNA compared with the fundus and corpus. However, similar levels of EP4 and FP receptor mRNA were observed comparing the fundus and LUS. Expression of EP2, EP3 and EP4 receptor mRNA were also detected in cervix, decidua and chorion. EP2 mRNA was most abundant in cervix, EP3 was most abimdant in myometrium and EP4 mRNA was most abundant in decidua. The variation in myometrial expression of genes encoding EP receptor sub-types paralleled the contractile responses of paired samples (reported elsewhere). 4 When expression of prostanoid receptor genes was studied in myometrium obtained from animals both in labour and not in labour and the techniques employed were optimized (principally the use of riboprobes), transcripts of similar size to the human genes were detected for prostanoid EP1, EP2, EP3, EP4, IP, FP and TP receptor mRNA using Northern blot. There were no gestational age related changes in expression of these genes. Expression of EP1, EP3 and IP receptor mRNA was significantly higher in myometrium from the fundus (compared with lower segment) whereas EP2 gene expression was significantly lower in the fundus. Labor was associated with a reduction in the regional variation of both EP2 and IP receptor gene expression, but not EP1 and EP3 expression. Labor was also associated with an overall lower level of expression of EP2 receptor mRNA. 5 When expression of prostanoid receptor genes was studied in cervix obtained from animals both in labour and not in labour, clear signals which were similar in estimated size to the human genes were detected by Northern analysis for EP1, EP2, EP3, EP4, FP, IP and TP receptors. Expression of the gene encoding the prostanoid EP? receptor increased with advancing gestational age prior to labor. Expression of the EP2, FP and TP receptor genes was much lower in animals that were delivered during spontaneous labor than in animals which were not in labor. 6 When expression of prostanoid receptor genes was studied in decidua and chorion obtained from animals both in labour and not in labour, expression of the genes encoding the EP1 and FP receptor in decidua and the EP4 receptor in chorion was lower with advancing gestational age. Expression of the EP? receptor gene was lower in labour in decidua, whereas expression of the IP receptor gene was higher in labour in both decidua (2-fold) and chorion (4-fold).

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Subjects: Q Science > QP Physiology
Colleges/Schools: College of Medical Veterinary and Life Sciences
Supervisor's Name: Nathanielsz, Prof. P.W. and Cameron, Prof. Iain T.
Date of Award: 2000
Depositing User: Mrs Marie Cairney
Unique ID: glathesis:2000-40962
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 23 Jan 2019 14:58
Last Modified: 23 Jan 2019 14:58
URI: http://theses.gla.ac.uk/id/eprint/40962
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