The role of the corpus luteum on placental development

There is robust evidence from human studies that support that pregnancies utilizing programmed, i.e., medicated frozen embryo transfers are at higher risk for several adverse maternal and fetal outcomes. While it has been postulated that these adverse outcomes originate from the lack of a functional corpus luteum (CL) during pregnancy, this has yet to be directly tested. This current gap in knowledge is likely due to the lack of a suitable animal model. Our proposed collaborative project will address this need, utilizing two novel non-human primate models that allow direct examination of first trimester CL and placental development. The main objective of this innovative application is to test the hypothesis that both the increased level of exogenous estradiol and the lack of a CL which occur in programmed cycle FET (p-FET) synergistically cause molecular changes in the early placenta development that predispose adverse pregnancy outcomes. To test this hypothesis, we will conduct in- depth placental phenotyping and molecular assessments to determine the cellular and molecular changes with p-FET in the first trimester placenta (Aim 1). We will also directly assess the protein and small molecules secreted into maternal circulation by the CL during the first trimester using cutting edge high throughput methodology to detect even low abundant molecules in CL and maternal blood samples (Aim 2). The Aims outlined in this application will provide extensive information for the field by improving understanding of how placental development is influenced by estradiol levels and other CL molecule signaling during the first trimester. Determining the causes of pregnancy loss, and pregnancy complications would greatly improve human health, reducing the associated physiological, psychological, and economic burdens and help us shape advances in maternal-fetal medicine. Project Number: 1R01HD121876-01 | Fiscal Year: 2026 | NIH Institute/Center: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | Principal Investigator: Lisa Vrooman | Institution: OREGON HEALTH & SCIENCE UNIVERSITY, PORTLAND, OR | Award Amount: $746,208 | Activity Code: R01 | Study Section: Pregnancy and Neonatology Study Section[PN] View on NIH RePORTER: https://reporter.nih.gov/project-details/11358850