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BackgroundThe human placenta is a rapidly developing organ that undergoes structural and functional changes throughout the pregnancy. Our objectives were to investigate the differences in global gene expression profile, the expression of imprinted genes and the effect of smoking in first and third trimester normal human placentas.Materials and MethodsPlacental samples were collected from 21 women with uncomplicated pregnancies delivered at term and 16 healthy women undergoing termination of pregnancy at 9–12 weeks gestation. Placental gene expression profile was evaluated by Human Genome Survey Microarray v.2.0 (Applied Biosystems) and real-time polymerase chain reaction.ResultsAlmost 25% of the genes spotted on the array (n = 7519) were differentially expressed between first and third trimester placentas. Genes regulating biological processes involved in cell proliferation, cell differentiation and angiogenesis were up-regulated in the first trimester; whereas cell surface receptor mediated signal transduction, G-protein mediated signalling, ion transport, neuronal activities and chemosensory perception were up-regulated in the third trimester. Pathway analysis showed that brain and placenta might share common developmental routes. Principal component analysis based on the expression of 17 imprinted genes showed a clear separation of first and third trimester placentas, indicating that epigenetic modifications occur throughout pregnancy. In smokers, a set of genes encoding oxidoreductases were differentially expressed in both trimesters.ConclusionsDifferences in global gene expression profile between first and third trimester human placenta reflect temporal changes in placental structure and function. Epigenetic rearrangements in the human placenta seem to occur across gestation, indicating the importance of environmental influence in the developing feto-placental unit.

Objective To study serial changes in maternal systemic and uterine artery haemodynamics and establish reference ranges for the second half of pregnancy.Design Prospective longitudinal observational study.Setting University hospital in Norway.Population Low-risk pregnant women.Methods Fifty-three low-risk pregnancies were evaluated at approximately 4-weekly intervals. Maternal systemic haemodynamics was assessed with impedance cardiography. Uterine artery blood velocity and diameter were measured using Doppler ultrasonography and uterine artery volume blood flow (Q uta ) was calculated as the product of mean velocity and crosssectional area of the uterine artery. The fraction of cardiac output (CO) distributed to the uterine circulation was calculated as: Q uta /CO · 100.Main outcome measures CO, Q uta , uterine vascular resistance (R uta ) and the fraction of CO distributed to the uterine circulation.Results The CO increased (P = 0.0063) until 34 weeks and remained stable until term. Total Q uta increased from 299 to 673 ml/minute and R uta halved from 0.26 to 0.13 mmHg/ml/ minute (P < 0.0001). The fraction of CO distributed to the uterine circulation increased from 5.6% to 11.7% (P < 0.0001).Conclusion During the second half of pregnancy, Q uta and the fraction of maternal CO distributed to the uterine circulation increase approximately two-fold, mainly as a result of decrease in R uta .

Please cite this paper as: Flo K, Wilsgaard T, Vårtun Å, Acharya G. A longitudinal study of the relationship between maternal cardiac output measured by impedance cardiography and uterine artery blood flow in the second half of pregnancy. BJOG 2010;117:837–844. Objective  To study serial changes in maternal systemic and uterine artery haemodynamics and establish reference ranges for the second half of pregnancy. Design  Prospective longitudinal observational study. Setting  University hospital in Norway. Population  Low‐risk pregnant women. Methods  Fifty‐three low‐risk pregnancies were evaluated at approximately 4‐weekly intervals. Maternal systemic haemodynamics was assessed with impedance cardiography. Uterine artery blood velocity and diameter were measured using Doppler ultrasonography and uterine artery volume blood flow (Quta) was calculated as the product of mean velocity and cross‐sectional area of the uterine artery. The fraction of cardiac output (CO) distributed to the uterine circulation was calculated as: Quta/CO × 100. Main outcome measures  CO, Quta, uterine vascular resistance (Ruta) and the fraction of CO distributed to the uterine circulation. Results  The CO increased (P = 0.0063) until 34 weeks and remained stable until term. Total Quta increased from 299 to 673 ml/minute and Ruta halved from 0.26 to 0.13 mmHg/ml/minute (P < 0.0001). The fraction of CO distributed to the uterine circulation increased from 5.6% to 11.7% (P < 0.0001). Conclusion  During the second half of pregnancy, Quta and the fraction of maternal CO distributed to the uterine circulation increase approximately two‐fold, mainly as a result of decrease in Ruta.

We evaluated global placental gene expression in intrauterine growth restriction (IUGR; n = 8) compared to normal pregnancies (n = 8) and studied possible additional effect of preeclampsia. Placental samples were collected from IUGR pregnancies due to placental insufficiency ascertained by hemodynamic studies. Four IUGR pregnancies were associated with preeclampsia. Gene expression profile was evaluated by 30k oligonucleotide microarrays. Principal component analysis (PCA) showed good separation in terms of gene expression patterns between the groups. Pathway analysis showed upregulation of inflammation mediated by chemokine and cytokine signaling pathway in the IUGR placentas. Genes involved in placental glucocorticoid metabolism were also differentially expressed. None of the known imprinted placental genes were differentially expressed. Subgroup analysis between IUGR placentas with and without preeclampsia showed few (n = 27) differentially expressed genes. In conclusion, IUGR due to placental insufficiency appears to alter placental glucocorticoid metabolism, upregulates inflammatory response in placenta, and shares common pathogenic mechanisms with severe early-onset preeclampsia.