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Biomolecules
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Embryo Implantation: New Molecular Insights in Endometrial Receptivity, Trophoblast Invasion...
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Embryo Implantation: New Molecular Insights in Endometrial Receptivity, Trophoblast Invasion and Signaling

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Reproduction".

Deadline for manuscript submissions: 15 July 2025 | Viewed by 3768

Special Issue Editors

Prof. Dr. Hans-Werner Denker

E-Mail Website
Guest Editor
Institute of Anatomy, Medical Faculty, University Duisburg-Essen, 45122 Essen, Germany
Interests: embryo implantation; endometrial receptivity; trophoblast; cell biology; developmental biology
Prof. Dr. Evdokia Dimitriadis

E-Mail Website
Guest Editor
Department of Obstetrics, Gynaecology and Newborn Health, University of Melbourne, Melbourne, VIC, Australia
Interests: endometrium; placenta; trophoblast; embryos; trophectoderm
Prof. Dr. Lois A. Salamonsen

E-Mail Website
Guest Editor
Centre for Reproductive Health, Hudson Institute of Medical Research, Department of Obstetrics and Gynaecology, Monash University, Melbourne, Australia
Interests: endometrial remodelling; embryo implantation; endometrial receptivity; menstruation

Special Issue Information

Dear Colleagues,

We are pleased to invite you to contribute to this Special Issue of Biomolecules. An impressive amount of molecular and cellular data has been accumulated in this field in recent years, making it timely to not only review these, but also achieve a better understanding of the biology of implantation. More than 30 years ago, a new approach was initiated in implantation research, transitioning from the previous dominance of endocrinology to asking cell biological questions, such as the EMT concept that was new at that time. With the advent of molecular approaches, omics technologies, sophisticated 3D in vitro models and more detailed insights into signaling processes, including those of extracellular vesicles, we believe it is time to provide a comprehensive overview, to ask what new insights can be obtained and what may be achieved in the coming decade.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but not limited to) the following:

  • The processes involved: epithelial transformation, decidual transformation, trophoblast differentiation, signaling (including extracellular vesicles), endometrial–embryo interactions, immune influence;
  • Emerging technologies: endometrial organoids (assembloids) and 3D cultures, endometrial stem cells, embryo mimics/trophoblast organoids and blastoids, endometrial multi-omics key pathways, single-cell omics and interactomes, spatial omics of the endometrium and implantation site;
  • Rethinking of established concepts: role of progesterone supplementation, recurrent implantation failure, ethics (using human organoids and embryoids in research), window of endometrial receptivity.

We look forward to receiving your contributions.

Prof. Dr. Hans-Werner Denker
Prof. Dr. Evdokia Dimitriadis
Prof. Dr. Lois A. Salamonsen
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • embryo implantation
  • endometrial receptivity
  • trophoblast invasion
  • signaling

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Published Papers (4 papers)

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Review

29 pages, 3410 KiB  
Review
HOXA10 and HOXA11 in Human Endometrial Benign Disorders: Unraveling Molecular Pathways and Their Impact on Reproduction
by Lorin-Manuel Pîrlog, Andrada-Adelaida Pătrășcanu, Mara-Diana Ona, Andreea Cătană and Ioana Cristina Rotar
Biomolecules 2025, 15(4), 563; https://doi.org/10.3390/biom15040563 - 10 Apr 2025
Viewed by 325
Abstract
HOX genes, a family of conserved transcription factors, are critical for reproductive tract development and endometrial functionality. This review highlights the molecular underpinnings of HOXA10/HOXA11 in reproductive health and their dysregulation in benign pathologies associated with infertility, such as endometriosis, adenomyosis, and endometrial [...] Read more.
HOX genes, a family of conserved transcription factors, are critical for reproductive tract development and endometrial functionality. This review highlights the molecular underpinnings of HOXA10/HOXA11 in reproductive health and their dysregulation in benign pathologies associated with infertility, such as endometriosis, adenomyosis, and endometrial polyps. These genes are dynamically regulated by estrogen and progesterone, with peak expression during the secretory phase of the menstrual cycle when implantation takes place. The molecular mechanisms underlying their action include the modulation of extracellular matrix (ECM) remodeling via metalloproteinases, cytokines like leukemia inhibitory factor, and cell adhesion molecules such as β3-integrin, all of which are essential for the differentiation of epithelial and stromal cells, as well as for trophoblast invasion. Aberrant HOX gene expression, driven by DNA hypermethylation or altered histone acetylation, compromises endometrial receptivity and implantation. For instance, reduced HOXA10 expression in endometriosis stems from hypermethylation and chronic inflammation, disrupting immune modulation and cytokine signaling. Similarly, adenomyosis alters HOXA11-regulated ECM remodeling and β3-integrin expression, impairing embryo attachment. Furthermore, regulatory pathways involving vitamin D and retinoic acid offer promising therapeutic avenues pathways, as they enhance HOXA10/HOXA11 expression and endometrial receptivity. This review underscores the critical molecular roles of HOXA10/HOXA11 genes as biomarkers and therapeutic targets to optimize fertility outcomes and address reproductive pathologies. Full article
(This article belongs to the Special Issue Embryo Implantation: New Molecular Insights in Endometrial Receptivity, Trophoblast Invasion and Signaling)
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24 pages, 3877 KiB  
Review
Revolutionizing Implantation Studies: Uterine-Specific Models and Advanced Technologies
by Shu-Yun Li and Francesco John DeMayo
Biomolecules 2025, 15(3), 450; https://doi.org/10.3390/biom15030450 - 20 Mar 2025
Viewed by 486
Abstract
Implantation is a complex and tightly regulated process essential for the establishment of pregnancy. It involves dynamic interactions between a receptive uterus and a competent embryo, orchestrated by ovarian hormones such as estrogen and progesterone. These hormones regulate proliferation, differentiation, and gene expression [...] Read more.
Implantation is a complex and tightly regulated process essential for the establishment of pregnancy. It involves dynamic interactions between a receptive uterus and a competent embryo, orchestrated by ovarian hormones such as estrogen and progesterone. These hormones regulate proliferation, differentiation, and gene expression within the three primary uterine tissue types: myometrium, stroma, and epithelium. Advances in genetic manipulation, particularly the Cre/loxP system, have enabled the in vivo investigation of the role of genes in a uterine compartmental and cell type-specific manner, providing valuable insights into uterine biology during pregnancy and disease. The development of endometrial organoids has further revolutionized implantation research. They mimic the native endometrial structure and function, offering a powerful platform for studying hormonal responses, implantation, and maternal-fetal interactions. Combined with omics technologies, these models have uncovered the molecular mechanisms and signaling pathways that regulate implantation. This review provides a comprehensive overview of uterine-specific genetic tools, endometrial organoids, and omics. We explore how these advancements enhance our understanding of implantation biology, uterine receptivity, and decidualization in reproductive research. Full article
(This article belongs to the Special Issue Embryo Implantation: New Molecular Insights in Endometrial Receptivity, Trophoblast Invasion and Signaling)
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23 pages, 1132 KiB  
Review
Endometrial Receptivity–Lessons from “Omics”
by Louie Ye and Evdokia Dimitriadis
Biomolecules 2025, 15(1), 106; https://doi.org/10.3390/biom15010106 - 11 Jan 2025
Cited by 2 | Viewed by 1331
Abstract
The window of implantation (WOI) is a critical phase of the menstrual cycle during which the endometrial lining becomes receptive and facilitates embryo implantation. Drawing on findings from various branches of “omics”, including genomics, epigenomics, transcriptomics, proteomics, lipidomics, metabolomics, and microbiomics, this narrative [...] Read more.
The window of implantation (WOI) is a critical phase of the menstrual cycle during which the endometrial lining becomes receptive and facilitates embryo implantation. Drawing on findings from various branches of “omics”, including genomics, epigenomics, transcriptomics, proteomics, lipidomics, metabolomics, and microbiomics, this narrative review aims to (1) discuss mechanistic insights on endometrial receptivity and its implication in infertility; (2) highlight advances in investigations for endometrial receptivity; and (3) discuss novel diagnostic and therapeutic strategies that may improve reproductive outcomes. Full article
(This article belongs to the Special Issue Embryo Implantation: New Molecular Insights in Endometrial Receptivity, Trophoblast Invasion and Signaling)
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16 pages, 1204 KiB  
Review
Blastocyst-Derived Lactate as a Key Facilitator of Implantation
by Kathryn H. Gurner and David K. Gardner
Biomolecules 2025, 15(1), 100; https://doi.org/10.3390/biom15010100 - 10 Jan 2025
Viewed by 1118
Abstract
The blastocyst develops a unique metabolism that facilitates the creation of a specialized microenvironment at the site of implantation characterized by high levels of lactate and reduced pH. While historically perceived as a metabolic waste product, lactate serves as a signaling molecule which [...] Read more.
The blastocyst develops a unique metabolism that facilitates the creation of a specialized microenvironment at the site of implantation characterized by high levels of lactate and reduced pH. While historically perceived as a metabolic waste product, lactate serves as a signaling molecule which facilitates the invasion of surrounding tissues by cancers and promotes blood vessel formation during wound healing. However, the role of lactate in reproduction, particularly at the implantation site, is still being considered. Here, we detail the biological significance of the microenvironment created by the blastocyst at implantation, exploring the origin and significance of blastocyst-derived lactate, its functional role at the implantation site and how understanding this mediator of the maternal–fetal dialogue may help to improve implantation in assisted reproduction. Full article
(This article belongs to the Special Issue Embryo Implantation: New Molecular Insights in Endometrial Receptivity, Trophoblast Invasion and Signaling)
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