In the past five years we characterized and identified mechanisms of abnormal trophoblast invasion in preeclampsia and supported the involvement of oxidative stress in the linkage of abnormal implantation to the systemic syndrome. This program extends the studies to detailed mechanistic examination and tests their long range significance to mother and baby. Abnormal implantation and reduced placental perfusion are insufficient to explain the syndrome. Apparently similar changes are present with pregnancies complicated by intrauterine growth restriction (IUGR) and one third of preterm pregnancy (PTB). Subproject 9 examines implantation in preeclampsia, IUGR and PTB in detail, proposing that differences in molecular mechanisms could explain why only preeclampsia results in the maternal syndrome. Project III proposes that reduced placental perfusion produces fetal/placental signals (one of which they propose to test is leptin) that alter maternal metabolism to increase nutrient delivery to the fetus. This beneficial metabolic change cannot be tolerated in some women and preeclampsia results. IUGR is the result of a blunting of this signal. Subproject 10 also concerns abnormal implantation, probing cellular mechanism responsible for their finding that the hypoxia inducible transcription factors HIF-1 alpha and HIF-2 alpha are increased in preeclampsia placentas due to slowed degradation and explores downstream products of HIF1a and HIF2a including leptin (Subproject 11) as one such product. They test is this reduced degradation is present in maternal and other fetal tissues. Subprojects 12 and 13 assess vascular functional changes in preeclampsia. Subprojects 12 and 13 propose a failure to increase maternal arterial compliance early in pregnancy predisposes the woman to higher sheer stresses, endothelial activation and increased oxidative stress. Project V measures global arterial compliance in high risk (prior preeclampsia) before during and after pregnancy, exploring the role of NO and activation of NADPH oxidase by components of the angiotensin response cascade including antibodies. Subprojects 122, 12, and 13 posit previously demonstrated reduced endothelial relaxation at this time in women with prior preeclampsia.
| Global Pregnancy Collaboration:; Schalekamp-Timmermans, Sarah; Arends, Lidia R et al. (2017) Fetal sex-specific differences in gestational age at delivery in pre-eclampsia: a meta-analysis. Int J Epidemiol 46:632-642 |
| Hux, Vanessa J; Roberts, James M; Okun, Michele L (2017) Allostatic load in early pregnancy is associated with poor sleep quality. Sleep Med 33:85-90 |
| Countouris, Malamo E; Schwarz, Eleanor B; Rossiter, Brianna C et al. (2016) Effects of lactation on postpartum blood pressure among women with gestational hypertension and preeclampsia. Am J Obstet Gynecol 215:241.e1-8 |
| Gandley, Robin E; Althouse, Andrew; Jeyabalan, Arundhathi et al. (2016) Low Soluble Syndecan-1 Precedes Preeclampsia. PLoS One 11:e0157608 |
| Tan, Hong Chang; Roberts, James; Catov, Janet et al. (2015) Mother's pre-pregnancy BMI is an important determinant of adverse cardiometabolic risk in childhood. Pediatr Diabetes 16:419-26 |
| Schmella, Mandy J; Clifton, Rebecca G; Althouse, Andrew D et al. (2015) Uric Acid Determination in Gestational Hypertension: Is it as Effective a Delineator of Risk as Proteinuria in High-Risk Women? Reprod Sci 22:1212-9 |
| Luiza, John W; Gallaher, Marcia J; Powers, Robert W (2015) Urinary cortisol and depression in early pregnancy: role of adiposity and race. BMC Pregnancy Childbirth 15:30 |
| Hux, Vanessa J; Roberts, James M (2015) A potential role for allostatic load in preeclampsia. Matern Child Health J 19:591-7 |
| Hassis, Maria E; Niles, Richard K; Braten, Miles N et al. (2015) Evaluating the effects of preanalytical variables on the stability of the human plasma proteome. Anal Biochem 478:14-22 |
| Catov, Janet M; Abatemarco, Diane; Althouse, Andrew et al. (2015) Patterns of gestational weight gain related to fetal growth among women with overweight and obesity. Obesity (Silver Spring) 23:1071-8 |
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