Regional variation in angiotensin converting enzyme activity in the human placenta.

Sensitivity of chorionic plate arteries to angiotensin II (AngII) is greatest at the placental periphery. Angiotensin converting enzyme (ACE) is central to the synthesis of AngII and is present in the placental vasculature. We measured vascular ACE activity/mg protein at 8-9 sites between the cord insertion and the periphery in 12 term placentae from normotensive, vaginally-delivered women. ACE increased from insertion to the periphery (P = 0.015); median ACE for each placenta was positively correlated with placental weight (P < 0.05) and placental:birthweight ratio (P < 0.02). We speculate that this may be related to fetal programming since placental:birthweight ratio is related to long-term health.

The ontogeny of components of the renin-angiotensin system in the porcine fetal ovary.

There is an autonomous renin-angiotensin system (RAS) in the adult ovary. Renin is present in the primitive kidney, and the fetal ovary develops from the nephrogenic ridge. We hypothesised that components of the ovarian RAS would be present from early gestation, with potential roles in ovarian development. We studied fetal pig ovaries from approximately day 45 (approximately 0.39 gestation) to term and measured mRNA (RT-PCR) for prorenin, angiotensinogen and the angiotensin II (AngII) Type 1 and 2 receptors (AT(1) and AT(2)), and protein expression (Western blot) and localization (immunohistochemistry) of the AT(1) and AT(2) receptors. mRNA for prorenin was present in relatively low abundance from at least day 45 and rose to approximately day 75 of gestation, whilst mRNA for angiotensinogen rose steadily. mRNA for the AT(1) receptor was present from approximately day 45 and did not alter significantly with increasing gestation but AT(2) receptor mRNA was initially high, falling sharply through pregnancy. The AT(1) receptor protein abundance fell steadily to term, whereas the AT(2) receptor protein did not change during gestation. Both receptors were localised in the surface epithelium and egg nests, the granulosa cells of primordial, primary and secondary follicles, and the oocytes of all except the secondary follicles. Collectively, our results support the hypothesis that there is a functional RAS in the fetal ovary from at least approximately day 45 of gestation until term and that it may have a paracrine role in ovarian growth and development.

Smoking in moderate/severe preeclampsia worsens pregnancy outcome, but smoking cessation limits the damage.

We studied phenotypic and clinical outcome data in an observational, multicenter cohort study of 1001 Western European white women and their singleton babies, with stringently defined moderate-to-severe preeclampsia. Ninety women admitted to being current smokers; 71 had stopped smoking before entry to the study. Across the categories of never-smoker, stopped, and current smoker there were significant increases in the proportion of women delivering before 34 weeks' gestation (P=0.011), delivering a baby below the third birth weight centile (P<0.001), or delivering a baby with any adverse outcome (P=0.011). By comparison with never-smokers, smoking during pregnancy was associated with a doubling of risk of being delivered before 34 weeks' (odds ratio: 1.98; 95% CI: 1.24 to 3.16; P=0.004), of delivering babies below the third centile of corrected birth weight (odds ratio: 2.20; 95% CI 1.41 to 3.44; P<0.0001), or for their babies to have any adverse outcome (odds ratio: 1.87; 95% CI: 1.19 to 2.95; P<0.006). Worryingly, the risk of developing eclampsia was increased 5-fold (odds ratio: 4.88; 95% CI: 1.44 to 16.61; P=0.005). The proportion of smokers in these preeclamptic women was lower than in our pregnant population generally. However, preeclampsia still carries significant perinatal morbidity, and cigarette smoking in preeclamptic pregnancies exacerbates this. Stopping smoking decreases the risks. Smoking in young women should be a particular target for advice by general practitioners before pregnancy, with active encouragement after conception to enroll in such trials as the current Smoking, Nicotine and Pregnancy Trial to support cessation.