Endometriosis is a sex hormone-dependent, painful disease that affects 10-15% of women worldwide with no definitive cure, and current treatments are not always effective. This limitation is mainly due to gaps in our knowledge about the mechanisms involved in the pathogenesis of endometriosis at the cellular and molecular levels. Hormonal dysregulation appears to be responsible for inflammation, angiogenesis, endometrial non-receptivity, embryo implantation failure and infertility in women with endometriosis. Although correlative evidence about possible causes of hormonal dysregulations exists, the functional mechanisms remain unknown. Reliable research models of endometriosis are needed to investigate the exact mechanisms that underlie hormone disruptions. This Commentary discusses the available in-vivo and in-vitro systems for studying endometriosis. The authors emphasize the recently developed human endometriosis organoids as cutting-edge and innovative research models for endometriosis investigations, discuss their advantages and describe challenges that must be addressed to yield a reliable in-vitro model of human endometriosis. Moreover, it discusses microfluidic technology to address the present challenges for producing advanced endometriosis organoids and how to benefit from CRISPR technology to improve our knowledge about disturbed hormonal function in patients with endometriosis.
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http://dx.doi.org/10.1016/j.rbmo.2022.03.016 | DOI Listing |
Int J Mol Sci
November 2024
Department of Life Science, Atlantic Technological University, Ash Lane, F91 YW50 Sligo, Ireland.
Endometriosis is an oestrogen-dependent inflammatory disease affecting menstruating women, with varying levels of severity. Oestrogen dysregulation is responsible for chronic inflammation, angiogenesis, endometrial lesion development, progression, and infertility during menarche in afflicted women. The inflammatory mediators associated with this chronic painful disease have been established, with research also indicating the relationship between dysbiosis and disease manifestation.
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November 2024
Laboratory of Translational Fertility Preservation, Department of Oncology and Pathology, Karolinska Institutet, 171 76 Stockholm, Sweden.
Endometrial disorders, such as infertility and endometriosis, significantly impact reproductive health, thus necessitating better models to study endometrial function. Current in vitro models fail to replicate the complexity of the human endometrium throughout the entire menstrual cycle. This study aimed to assess the physiological response of human endometrial organoids (hEOs) to in vitro hormonal treatments designed to mimic the hormonal fluctuations of the menstrual cycle.
View Article and Find Full Text PDFInt J Mol Sci
July 2024
Department of Biomedical Sciences, School of Medicine, Nazarbayev University, 5/1 Kerey and Zhanibek Khans St, Astana 020000, Kazakhstan.
Endometriosis is a hormone-dependent, chronic inflammatory condition that affects 5-10% of reproductive-aged women. It is a complex disorder characterized by the growth of endometrial-like tissue outside the uterus, which can cause chronic pelvic pain and infertility. Despite its prevalence, the underlying molecular mechanisms of this disease remain poorly understood.
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June 2024
Molecular Medicine Department (DMM), Centre for Health Technologies (CHT), Unità di Ricerca (UdR) INSTM, University of Pavia, 27100 Pavia, Italy.
Over the past decade, the development of three-dimensional (3D) models has increased exponentially, facilitating the unravelling of fundamental and essential cellular mechanisms by which cells communicate with each other, assemble into tissues and organs and respond to biochemical and biophysical stimuli under both physiological and pathological conditions. This section presents a concise overview of the most recent updates on the significant contribution of different types of 3D cell cultures including spheroids, organoids and organ-on-chip and bio-printed tissues in advancing our understanding of cellular and molecular mechanisms. The case studies presented include the 3D cultures of breast cancer (BC), endometriosis, the liver microenvironment and infections.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
May 2024
Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030.
EPH receptors (EPHs), the largest family of tyrosine kinases, phosphorylate downstream substrates upon binding of ephrin cell surface-associated ligands. In a large cohort of endometriotic lesions from individuals with endometriosis, we found that and expressions are increased in endometriotic lesions relative to normal eutopic endometrium. Because signaling through EPHs is associated with increased cell migration and invasion, we hypothesized that chemical inhibition of EPHA2/4 could have therapeutic value.
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