Conservation at the uterine–placental interface

Abstract

The hemochorial placentation site is characterized by a dynamic interplay between trophoblast cells and maternal cells. These cells cooperate to establish an interface required for nutrient delivery to promote fetal growth. In the human, trophoblast cells penetrate deep into the uterus. This is not a consistent feature of hemochorial placentation and has hindered the establishment of suitable animal models. The rat represents an intriguing model for investigating hemochorial placentation with deep trophoblast cell invasion. In this study, we used single-cell RNA sequencing to characterize the transcriptome of the invasive trophoblast cell lineage, as well as other cell populations within the rat uterine–placental interface during early (gestation day [gd] 15.5) and late (gd 19.5) stages of intrauterine trophoblast cell invasion. We identified a robust set of transcripts that define invasive trophoblast cells, as well as transcripts that distinguished endothelial, smooth muscle, natural killer, and macrophage cells. Invasive trophoblast, immune, and endothelial cell populations exhibited distinct spatial relationships within the uterine–placental interface. Furthermore, the maturation stage of invasive trophoblast cell development could be determined by assessing gestation stage–dependent changes in transcript expression. Finally, and most importantly, expression of a prominent subset of rat invasive trophoblast cell transcripts is conserved in the invasive extravillous trophoblast cell lineage of the human placenta. These findings provide foundational data to identify and interrogate key conserved regulatory mechanisms essential for the development and function of an important compartment within the hemochorial placentation site that is essential for a healthy pregnancy.

Cell type and cell signaling innovations underlying mammalian pregnancy

“…Cells identified as extraplacental trophoblast (Cp_iEPT) expressed CXCL12, PENK, FLT1, IL34 , and ADAM19 , as well as the genes QSOX1, CNFN, and GPC1 , which were shared with human endovascular EVT and mouse spiral artery-remodeling giant cells ( Figure 2a ). GPC1 has been identified in the most deeply invasive trophoblast of the rat 26 and linked to angiogenesis and invasion 27 : we observed GPC1 + cells, likely Cp_iEPT, close to the maternal vasculature and the myometrium ( Figure 2b ). Another extraplacental cell cluster was distinguished by specific expression of oxytocin (Cp_EPT-OXT).…”

Notum-Mediated WNT Silencing Drives Extravillous Trophoblast Cell Lineage Development

“…In contrast, NOTUM appears to be a species-specific regulator of the invasive trophoblast cell lineage, which may be best exemplified in comparing rat with human placentation. The rat exhibits robust intrauterine trophoblast cell invasion ( 46, 47 ) but invasive trophoblast cells do not express detectable NOTUM, instead rat invasive trophoblast cells express other WNT signaling antagonists, including catenin beta interacting protein 1 ( CTNNBIP1 ) and NKD inhibitor of WNT signaling pathway 1 ( NKD1 ) ( 48 ). It remains to be determined whether and how WNT signaling and WNT antagonists may modulate development and function of the rat invasive trophoblast cell lineage.…”

Single-cell insights into development of the bovine placenta

“…Single-cell transcriptomics has revolutionized the ability to characterize complex cell populations, discover novel cell types and states, and unravel complex cellular processes governing development and function of tissues and organs [30]. This technology has been used to define new developmental processes involved in morphogenesis of the human and rodent placentae [31][32][33][34] as well as recently, the cotyledon and intercotyledon areas of the mature bovine placenta [35]. Here, single-cell transcriptome analysis was used to understand the development of the bovine conceptus during the first 2 months of pregnancy.…”