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S.J. Lye
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M.E. Wlodek
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J.R.G. Challis
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ABSTRACT

Uterine contractions, induced by the administration of oxytocin to sheep between d 123-144 of pregnancy, were associated with a mean transient decrease in fetal PaO2 of 2.8 mm Hg within 5 min. These changes were associated with a rapid increase in the concentration of ACTH in fetal plasma. There was a significant (P<0.05) increase in the percentage change (+40 to +47%) over basal ACTH levels in fetal plasma at +5, +15 and +20 min after oxytocin. Administration of saline had no significant effect on intrauterine pressure, fetal PaO2 or fetal plasma ACTH levels. We speculate that increases in uterine activity and/or transient decreases in fetal PaO2 may contribute to short-term fluctuations in plasma ACTH in fetal sheep.

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Melanie Tran
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Linda A Gallo
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Andrew J Jefferies
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Karen M Moritz Department of Physiology, School of Biomedical Sciences, The University of Melbourne, Parkville, Victoria 3010, Australia

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Mary E Wlodek
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Intrauterine growth restriction increases adult metabolic disease risk with evidence to suggest that suboptimal conditions in utero can have transgenerational effects. We determined whether impaired glucose tolerance, reduced insulin secretion, and pancreatic deficits are evident in second-generation (F2) male and female offspring from growth-restricted mothers, in a rat model of uteroplacental insufficiency. Late gestation uteroplacental insufficiency was induced by bilateral uterine vessel ligation (restricted) or sham surgery (control) in Wistar-Kyoto rats. First-generation (F1) control and restricted females were mated with normal males and F2 offspring studied at postnatal day 35 and at 6 and 12 months. F2 glucose tolerance, insulin secretion, and sensitivity were assessed at 6 and 12 months and pancreatic morphology was quantified at all study ages. At 6 months, F2 restricted male offspring exhibited blunted first-phase insulin response (−35%), which was associated with reduced pancreatic β-cell mass (−29%). By contrast, F2 restricted females had increased β-cell mass despite reduced first-phase insulin response (−38%). This was not associated with any changes in plasma estradiol concentrations. Regardless of maternal birth weight, F2 control and restricted males had reduced homeostatic model assessment of insulin resistance and elevated plasma triglyceride concentrations at 6 months and reduced whole-body insulin sensitivity at 6 and 12 months compared with females. We report that low maternal birth weight is associated with reduced first-phase insulin response and gender-specific differences in pancreatic morphology in the F2. Further studies will define the mode(s) of disease transmission, including direct insults to developing gametes, adverse maternal responses to pregnancy, or inherited mechanisms.

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N E Curtis
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P W M Ho
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R G King
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W Farrugia
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E K Moses
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M T Gillespie
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J M Moseley
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G E Rice
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M E Wlodek
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Abstract

Parathyroid hormone-related protein (PTHrP) gene expression and/or immunoreactive protein have previously been identified in the uterus and intrauterine gestational tissues. The putative roles of PTHrP during pregnancy include vasodilatation, regulation of placental calcium transfer, uterine smooth muscle relaxation and normal fetal development. The aims of this study were 1) to determine the tissue-specific and temporal expression of PTHrP mRNA and immunoreactive protein in human gestational tissues collected at preterm and term; and 2) to determine the effect of labour on PTHrP expression by collecting these tissues from women undergoing elective caesarean section (before labour), intra-partum caesarean section during spontaneous-onset labour (during labour), and women with spontaneous labour and normal vaginal delivery (after labour). Total RNA and protein were extracted from placenta, amnion (over placenta and reflected) and choriodecidua for analysis by Northern blot (using a specific human PTHrP cDNA probe), and by N-terminal PTHrP RIA respectively. In amnion over placenta, reflected amnion and choriodecidua both PTHrP mRNA relative abundance and immunoreactive protein were significantly elevated at term compared with preterm (P<0·01). At term, both PTHrP and its mRNA were significantly greater in amnion than in placenta and choriodecidua (P<0·05). Also, both PTHrP and its mRNA were significantly elevated in amnion over placenta compared with reflected amnion (P<0·05). The expression of PTHrP and its mRNA did not change in association with term labour or rupture of the fetal membranes, therefore this study provides no evidence for a specific PTHrP role in the onset and/or maintenance of term labour. However, the significant up-regulation of PTHrP mRNA and protein in the fetal membranes at term compared with preterm suggests an important role in late human pregnancy.

Journal of Endocrinology (1997) 154, 103–112

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