A method to isolate syncytiotrophoblast-derived medium-large extracellular vesicle small RNA from maternal plasma.

Syncytiotrophoblast-derived extracellular vesicles (STB-EVs) have an important role in placental research: both as mediators of feto-maternal signalling and as liquid biopsies reflecting placental health. Recent evidence highlights the importance of STB-EV RNA. Isolation of STB-EV RNA from maternal blood is therefore an important challenge. We describe a novel technique where we first separate medium-large particles from plasma using centrifugation then use a highly specific bead-bound antibody to placental alkaline phosphatase to separate STB-EVs from other similar-sized particles. We demonstrate the yield and size profile of small RNA obtained from plasma STB-EVs. We present data confirming isolation of placenta-derived micro RNA from maternal plasma using this method. The technique has been successfully applied to validate novel RNA discoveries from placental perfusion models. We propose it could offer new insights through transcriptomic analyses, providing a syncytiotrophoblast-specific signal from maternal blood.

Auto-antibodies against the angiotensin II type I receptor in women with uteroplacental acute atherosis and preeclampsia at delivery and several years postpartum.

BACKGROUND: Uteroplacental acute atherosis is a pregnancy-specific lesion resembling early stages of atherosclerosis found frequently in preeclampsia. Preeclampsia is associated with an increased risk for future maternal atherosclerotic cardiovascular disease. The renin-angiotensin-system plays a role both in atherosclerosis and in preeclampsia. Circulating agonistic autoantibodies at the angiotensin-II type 1 receptor (AT1-AA) are increased in preeclampsia. We hypothesized an association between AT1-AA at delivery and postpartum with acute atherosis in pregnancy. MATERIAL AND METHODS: Maternal serum and decidua basalis tissue was collected at elective cesarean section (n = 41; 24 preeclampsia, 17 normotensive controls). Circulating AT1-AA were detected by a bioassay using spontaneously beating rat cardiomyocytes at delivery (n = 41) and 5-8 years postpartum in a subgroup (n = 10). Decidual acute atherosis was assessed by immunohistochemistry. RESULTS: Significantly less normotensive controls (18%; 3/17) than women with preeclampsia (58%; 14/24) were AT1-AA positive at delivery, p<0.01. Uteroplacental acute atherosis and circulating AT1-AA at delivery were not significantly correlated. Postpartum, 2 prior preeclamptic women had circulating AT1-AA, both without acute atherosis in pregnancy. CONCLUSIONS: Our results confirm that circulating AT1-AA are present significantly more often in preeclampsia than in normotensive pregnancy, however without association to acute atherosis. Whether circulating maternal AT1-AA or acute atherosis target young women at increased long-term cardiovascular risk warrants further investigations.

Gestational changes in iodine status in a cohort study of pregnant women from the United Kingdom: season as an effect modifier.

BACKGROUND: Iodine is required throughout pregnancy for thyroid hormone production, which is essential for fetal brain development. Studies of iodine status in pregnant women from the United Kingdom (UK) have focused on early gestation (<16 wk). Data on the effect of advancing gestation on urinary iodine excretion are conflicting, with suggestions of both an increase and a decrease. OBJECTIVES: The aims were to evaluate iodine status in a cohort of UK pregnant women and to explore how it changes throughout gestation. DESIGN: We used samples and data from 230 UK pregnant women who were recruited to the Selenium in PRegnancy INTervention study. Iodine concentration was measured in spot-urine samples that were collected at ∼12, 20, and 35 wk of gestation; creatinine concentration was also measured to correct for urine dilution. A linear mixed model was used to explore the effect of gestational week on iodine-to-creatinine ratio, with change in season, body mass index, daily milk intake, and maternal age controlled for. RESULTS: The median urinary iodine concentration from urine samples collected at all time points (n = 662) was 56.8 µg/L, and the iodine-to-creatinine ratio was 116 µg/g, thus classifying this cohort as mildly-to-moderately iodine deficient. The median iodine-to-creatinine ratios at 12, 20, and 35 wk were 102.5, 120.0, and 126.0 µg/g, respectively. Only 3% of women were taking iodine-containing prenatal supplements. The iodine-to-creatinine ratio increased with advancing gestation, and there was a significant interaction between gestational week and season (P = 0.026). For a 1-wk increase in gestation, the iodine-to-creatinine ratio increased by a factor of 1.05 (95% CI: 1.02, 1.08) in winter and by a factor of 1.04 (95% CI: 1.00, 1.08) in summer. CONCLUSIONS: This group of UK pregnant women was mildly-to-moderately iodine deficient at all trimesters, which is of public health concern. The finding that the iodine-to-creatinine ratio increased over the course of gestation may not be generalizable to populations with different iodine status from ours and merits further investigation. This trial was registered at www.isrctn.com as ISRCTN37927591.