In vitro models of the human endometrium: evolution and application for women’s health+

Fitzgerald, Harriet C.; Schust, Danny J.; Spencer, Thomas E.

doi:10.1093/biolre/ioaa183

Cited by 51 publications

(35 citation statements)

References 90 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thus, there is a need to establish multicellular models that mimic the process of implantation. To overcome these limitations, several investigators have developed in vitro models of embryo/endometrium interaction where two or more cellular components are evaluated (69,(78)(79)(80)(81). We established a 3D in vitro model of the human endometrium consisting of hESC within an extracellular matrix and trophoblast cells as the main component of a BLS that lacks the inner cell layer (19,33).…”

Section: Discussionmentioning

confidence: 99%

TNF-α Regulated Endometrial Stroma Secretome Promotes Trophoblast Invasion

et al. 2021

View full text Add to dashboard Cite

Successful implantation requires the coordinated migration and invasion of trophoblast cells from out of the blastocyst and into the endometrium. This process relies on signals produced by cells in the maternal endometrium. However, the relative contribution of stroma cells remains unclear. The study of human implantation has major technical limitations, therefore the need of in vitro models to elucidate the molecular mechanisms. Using a recently described 3D in vitro models we evaluated the interaction between trophoblasts and human endometrial stroma cells (hESC), we assessed the process of trophoblast migration and invasion in the presence of stroma derived factors. We demonstrate that hESC promotes trophoblast invasion through the generation of an inflammatory environment modulated by TNF-α. We also show the role of stromal derived IL-17 as a promoter of trophoblast migration through the induction of essential genes that confer invasive capacity to cells of the trophectoderm. In conclusion, we describe the characterization of a cellular inflammatory network that may be important for blastocyst implantation. Our findings provide a new insight into the complexity of the implantation process and reveal the importance of inflammation for embryo implantation.

show abstract

Section: Discussionmentioning

confidence: 99%

TNF-α Regulated Endometrial Stroma Secretome Promotes Trophoblast Invasion

et al. 2021

View full text Add to dashboard Cite

show abstract

“…3A and Dataset S2). It is worth noting that the same Matrigel batch was used throughout this study, to avoid potential lot-to-lot variation (8). In total, 374 metabolites were identified, of which 172 were EEO-derived, i.e., absent from both CM and MCM (Fig.…”

Section: Significancementioning

confidence: 99%

“…Despite UF being the site of critical reproductive events, including sperm migration, embryo implantation, and conceptus development, our understanding of the mechanisms governing UF formation and composition regulation is poor. This is largely attributable to ethical (6) and technical (7) limitations surrounding human UF interrogation in vivo, in addition to inadequate cell culture techniques recapitulating UF formation in vitro (8). Regarding the former, several available methods for sampling UF from animals, such as in situ cannulation, perfusion, and excision and rapid sampling (7), are not transferable to women.…”

mentioning

confidence: 99%

Capture and metabolomic analysis of the human endometrial epithelial organoid secretome

Simintiras

Dhakal

Ranjit

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Suboptimal uterine fluid (UF) composition can lead to pregnancy loss and likely contributes to offspring susceptibility to chronic adult-onset disorders. However, our understanding of the biochemical composition and mechanisms underpinning UF formation and regulation remain elusive, particularly in humans. To address this challenge, we developed a high-throughput method for intraorganoid fluid (IOF) isolation from human endometrial epithelial organoids. The IOF is biochemically distinct to the extraorganoid fluid (EOF) and cell culture medium as evidenced by the exclusive presence of 17 metabolites in IOF. Similarly, 69 metabolites were unique to EOF, showing asymmetrical apical and basolateral secretion by the in vitro endometrial epithelium, in a manner resembling that observed in vivo. Contrasting the quantitative metabolomic profiles of IOF and EOF revealed donor-specific biochemical signatures of organoids. Subsequent RNA sequencing of these organoids from which IOF and EOF were derived established the capacity to readily perform organoid multiomics in tandem, and suggests that transcriptomic regulation underpins the observed secretory asymmetry. In summary, these data provided by modeling uterine luminal and basolateral fluid formation in vitro offer scope to better understand UF composition and regulation with potential impacts on female fertility and offspring well-being.

show abstract

“…To uncover the molecular mechanisms that determine the mechanical cross-talk between the developing human embryo and endometrium during implanta-tion, in vitro systems must be further developed (see the recent review in [127]). These approaches may involve novel 3D co-culture systems (e.g., [128]) and hormone-sensitive endometrial organoids (e.g., [129][130][131]; see recent reviews in [132,133]).…”

Section: Discussionmentioning

confidence: 99%

How Mechanical Forces Change the Human Endometrium during the Menstrual Cycle in Preparation for Embryo Implantation

Sternberg

Buck

Claßen-Linke

et al. 2021

Cells

View full text Add to dashboard Cite

The human endometrium is characterized by exceptional plasticity, as evidenced by rapid growth and differentiation during the menstrual cycle and fast tissue remodeling during early pregnancy. Past work has rarely addressed the role of cellular mechanics in these processes. It is becoming increasingly clear that sensing and responding to mechanical forces are as significant for cell behavior as biochemical signaling. Here, we provide an overview of experimental evidence and concepts that illustrate how mechanical forces influence endometrial cell behavior during the hormone-driven menstrual cycle and prepare the endometrium for embryo implantation. Given the fundamental species differences during implantation, we restrict the review to the human situation. Novel technologies and devices such as 3D multifrequency magnetic resonance elastography, atomic force microscopy, organ-on-a-chip microfluidic systems, stem-cell-derived organoid formation, and complex 3D co-culture systems have propelled the understanding how endometrial receptivity and blastocyst implantation are regulated in the human uterus. Accumulating evidence has shown that junctional adhesion, cytoskeletal rearrangement, and extracellular matrix stiffness affect the local force balance that regulates endometrial differentiation and blastocyst invasion. A focus of this review is on the hormonal regulation of endometrial epithelial cell mechanics. We discuss potential implications for embryo implantation.

show abstract

In vitro models of the human endometrium: evolution and application for women’s health+

Cited by 51 publications

References 90 publications

TNF-α Regulated Endometrial Stroma Secretome Promotes Trophoblast Invasion

TNF-α Regulated Endometrial Stroma Secretome Promotes Trophoblast Invasion

Capture and metabolomic analysis of the human endometrial epithelial organoid secretome

How Mechanical Forces Change the Human Endometrium during the Menstrual Cycle in Preparation for Embryo Implantation

Contact Info

Product

Resources

About