Abstract
There is evidence that fetal growth restriction is associated with impaired nephrogenesis and reduced numbers of mature nephrons at birth. It has been proposed that such impairment of renal growth may contribute to increased blood pressure in later life. Although prostaglandins (PG) play a key role in kidney development, it is unknown whether a poor fetal substrate supply alters the synthesis or actions of PG within the fetal kidney. Using real-time reverse transcriptase PCR, we have measured the effect of chronic placental restriction (PR) on the renal expression of PG endoperoxide G/H synthase-2 (PGHS-2), PGE2 receptors EP2 and EP4, and renin mRNA in the sheep fetus in late gestation. Restriction of placental growth reduced fetal body weight (PR: 3.2 ± 0.2 kg, control: 4.8 ± 0.2 kg) and total kidney weight (PR: 19.7 ± 1.8 g, control: 25.1 ± 1.3 g). Mean fetal arterial Po2 was reduced by PR (PR: 15.03 ± 0.67 mm Hg, control: 21.3 ± 0.87 mm Hg). Renal PGHS-2 mRNA was increased in the PR group (PR: 2.26 ± 0.38, control: 1.20 ± 0.31) and was inversely related to mean fetal arterial Po2 in the PR and control groups [PGHS-2: −0.17 (Po2) + 4.69, r2 = 0.26]. PR also increased renal EP2 (PR: 1.57 + 0.24, control: 0.82 + 0.13) but not EP4 mRNA. Renin mRNA was directly related to renal EP2 [renin = 0.37 (EP2) + 0.97, r2 = 0.29] and EP4, [renin = 0.75 (EP4) + 0.44, r2 = 0.38] mRNA expression. Thus, the restriction of placental growth and associated chronic hypoxemia appear to increase the renal capacity to synthesize and respond to PG, which may play an important role in maintaining renin mRNA expression in the growth-restricted fetus.
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Supported by a grant from the Molly Towell Perinatal Research Foundation, the Canadian Institutes of Health Research, the Alberta Heritage Foundation for Medical Research, and the National Health and Medical Research Council of Australia.
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Williams, S., McMillen, I., Zaragoza, D. et al. Placental Restriction Increases the Expression of Prostaglandin Endoperoxide G/H Synthase-2 and EP2 mRNA in the Fetal Sheep Kidney during Late Gestation. Pediatr Res 52, 879–885 (2002). https://doi.org/10.1203/00006450-200212000-00012
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DOI: https://doi.org/10.1203/00006450-200212000-00012
