Division of Reproductive, Stem Cell and Perinatal Biology
Our Studies
The Remarkable Process of Human Placental Development
We study the remarkable process of human placental development. Interestingly, while the placenta is one of the defining characteristics of mammals, the architecture and development of the mamalian placenta is nothighly conserved. The human placenta is one of the most invasive placentas and results in the formation of an organ which comprises cells both from the fetus and the mother. How this chimeric organ forms and is not rejected is truly remarkable. The fetal cells dramatically remodel the maternal vasculature to bring large volumes of maternal blood to the placenta. The mechanisms that regulate both interstitial and endovascular invasion are not fully understood.
Our focus is on the invasive component of the placenta, the region known as the basal plate or decidua basalis.
Diagram of the human maternal-fetal interface. A: Representation of the human placenta after delivery. The placental surface that was adjacent to the uterine wall is termed the basal platedenoted ny the boxed area. B: View of the basal plate at the cellular level. This chimeric region of the placenta is composed of both maternal and fetal components: extravillous (invasive) cytotrophoblasts (dark gray), decidual cells (light gray), remodeled vasculature (both invasive CTBs and maternal endothelium) and maternal immune cells (white).
Image Credit: Winn, et. al. Endocrinology. 2007 Mar.
We utilize several in vitro models to study cytotrophoblast differentiation and invasion:
1. Primary Cytotrophoblast in vitro Differentiation - Cytotrophoblasts isolated from placenta and plated on an extracellular matrix which initiates differentiation down the invasive pathway (red).
2. Villous Explant Model - Anchoring chorionic villi are dissected and plated on an extracellular matrix. After one round of proliferation, the trophoblasts from the cell column, differentiate and invade into the extracellular matrix (blue).
Illustration of two in vitro models for studying human cytotrophoblast invasion: (A) When human cytotrophoblasts (light green cells encircled in red) are isolated from early-gestation placentas and plated on an extracellular matrix (ECM) substrate (Matrigel), they differentiate along the pathway that leads to uterine invasion. By 12 hours in culture these cells form aggregates that resemble cell columns of anchoring villi, and by 48 hours they switch on expression of a repertoire of stage-specific antigens that are expressed in cytotrophoblasts within the uterine wall in situ (dark green cells). These molecules facilitate uterine invasion, vascular mimicry, and evasion of the maternal immune response. (B) When anchoring villi are dissected from the surfaces of early-gestation human placentas (blue box) and plated on an ECM substrate, cytotrophoblasts in cell columns continue to differentiate. By 48 hours many cytotrophoblasts have left the columns and invaded the substrate (green box). During this process they execute the same phenotypic switch that isolated cells carry out.
Image credit: Red-Horse K, et. al. Trophoblast differentiation during embryo implantation and formation of the maternal-fetal interface. J Clin Invest. 2004 Sep;114(6):744-54.
Microarrays - We have also used a global approach for understanding gene expression at the basal plate. We have completed two analyses looking at this region over gestation and in pathologic cases of preeclampsia, a common pregnancy complication that results in significant maternal and neonatal morbidity and mortality.
Genes Differentially Expressed in the Basal Plate of Placentas From PE Pregnancies: Color Map of Differentially Expressed Genes. The normalized log intensity values for all 71 DE probesets were centered to the median value of each probeset and colored on a range of –2.5 to +2.5. Red denotes upregulated and green denotes downregulated expression as compared to the median value. Rows contain data from a single basal plate specimen and columns correspond to a single probeset. Samples are arranged from bottom to top, ordered by increasing gestational age within each category. Columns are rank ordered by fold change [mean PE value (n=12) divided by mean PTL value (n=11)] from left to right.