Characteristics of the endometrium in menstruating species: lessons learned from the animal kingdom†

Catalini, Laura; Fedder, Jens

doi:10.1093/biolre/ioaa029

Cited by 20 publications

(12 citation statements)

References 69 publications

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“…2c ). Apes, Old World monkeys, and some New World monkeys undergo a menstrual cycle characterised by external bleeding due to shedding of the outermost layer (menses) 24 . Most other mammalian species experience an oestrous cycle, in which the uterus undergoes remodelling throughout the cycle without shedding 25 .…”

Section: Anatomy and Function Of The Uterusmentioning

confidence: 99%

Building a stem cell-based primate uterus

et al. 2021

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The uterus is the organ for embryo implantation and fetal development. Most current models of the uterus are centred around capturing its function during later stages of pregnancy to increase the survival in pre-term births. However, in vitro models focusing on the uterine tissue itself would allow modelling of pathologies including endometriosis and uterine cancers, and open new avenues to investigate embryo implantation and human development. Motivated by these key questions, we discuss how stem cell-based uteri may be engineered from constituent cell parts, either as advanced self-organising cultures, or by controlled assembly through microfluidic and print-based technologies.

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Section: Anatomy and Function Of The Uterusmentioning

confidence: 99%

Building a stem cell-based primate uterus

et al. 2021

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“…The majority of immunological endometriosis research is performed on animals. In nature, spontaneous endometriosis affects only those mammalian species that menstruate, including: primates, some bat species, the spiny mouse and elephant shrew [47]. Many animal models are not fully reliable, since endometriosis is induced artificially and does not represent all the phenomena present in the disorder.…”

Section: Immunosuppressive Treatmentmentioning

confidence: 99%

Immunology and Immunotherapy of Endometriosis

Maksym

Hoffmann-Młodzianowska

Skibińska

et al. 2021

JCM

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Endometriosis is one of the most common gynecological and systemic diseases, with a remarkable immune background. Patients suffer from pain and fertility reduction. Due to the distinct immune component, an immunotherapeutic approach may gain importance in the future. In endometriosis, shifts in the cell fractions of the immune system are well known. Moreover, hypoxia concomitant with inflammation causes a disturbed immune response. The removal of endometriosis has a therapeutic effect, normalizes the immune disorders, and remains the most effective causative treatment in terms of pain and infertility. A key issue is whether a similar effect can be achieved for fertility with non-invasive immunotherapy where surgery is inadvisable or cannot be performed for various reasons. Numerous immunotherapy trials, including vaccines, were conducted on animals only, although the research is encouraging. Among the promising methods of non-specific immunotherapy is the administration of an ethiodized oil contrast. Moreover, due to the significant successes of immunotherapy in oncology, the possibility of immunotherapy affecting NK cells has been postulated. NK cells are responsible for the surveillance and apoptosis of ectopic cells. Expanding the arsenal of endometriosis treatment by immunotherapy is promising due to the significant contribution of immunological factors and the limitations of current treatment methods.

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“…Although numerous animal studies have demonstrated the cyclic physiology of the endometrium, there remain substantial discrepancies among different species. Moreover, the lack of a physiologically relevant in- vitro model for the endometrium, with the given practical difficulties associated with access to primary cells and in- vitro maintenance of the multi-layered culture system, remains the main obstacle for research, suggesting the need for a more physiologically relevant model for the human endometrium ( McGowen et al , 2014 ; Catalini and Fedder, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Three-dimensional microengineered vascularised endometrium-on-a-chip

Ahn

Yoon

Hong³

et al. 2021

Human Reproduction

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STUDY QUESTION Can we reconstitute physiologically relevant 3-dimensional (3D) microengineered endometrium in-vitro model? SUMMARY ANSWER Our representative microengineered vascularised endometrium on-a-chip closely recapitulates the endometrial microenvironment that consists of three distinct layers including epithelial cells, stromal fibroblasts and endothelial cells in a 3D extracellular matrix in a spatiotemporal manner. WHAT IS KNOWN ALREADY Organ-on-a-chip, a multi-channel 3D microfluidic cell culture system, is widely used to investigate physiologically relevant responses of organ systems. STUDY DESIGN, SIZE, DURATION The device consists of five microchannels that are arrayed in parallel and partitioned by array of micropost. Two central channels are for 3D culture and morphogenesis of stromal fibroblast and endothelial cells. In addition, the outermost channel is for the culture of additional endometrial stromal fibroblasts that secrete biochemical cues to induce directional pro-angiogenic responses of endothelial cells. To seed endometrial epithelial cells, on Day 8, Ishikawa cells were introduced to one of the two medium channels to adhere on the gel surface. After that, the microengineered endometrium was cultured for an additional 5–6 days (total ∼ 14 days) for the purpose of each experiment. PARTICIPANTS/MATERIALS, SETTING, METHODS Microfluidic 3D cultures were maintained in endothelial growth Medium 2 with or without oestradiol and progesterone. Some cultures additionally received exogenous pro-angiogenic factors. For the three distinct layers of microengineered endometrium-on-a-chip, the epithelium, stroma and blood vessel characteristics and drug response of each distinct layer in the microfluidic model were assessed morphologically and biochemically. The quantitative measurement of endometrial drug delivery was evaluated by the permeability coefficients. MAIN RESULTS AND THE ROLE OF CHANCE We established microengineered vascularised endometrium-on-chip, which consists of three distinct layers: epithelium, stroma and blood vessels. Our endometrium model faithfully recapitulates in-vivo endometrial vasculo-angiogenesis and hormonal responses displaying key features of the proliferative and secretory phases of the menstrual cycle. Furthermore, the effect of the emergency contraception drug levonorgestrel was evaluated in our model demonstrating increased endometrial permeability and blood vessel regression in a dose-dependent manner. We finally provided a proof of concept of the multi-layered endometrium model for embryo implantation, which aids a better understanding of the molecular and cellular mechanisms underlying this process. LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION This report is largely an in-vitro study and it would be beneficial to validate our findings using human primary endometrial cells. WIDER IMPLICATIONS OF THE FINDINGS Our 3D microengineered vascularised endometrium-on-a-chip provides a new in-vitro approach to drug screening and drug discovery by mimicking the complicated behaviours of human endometrium. Thus, we suggest our model as a tool for addressing critical challenges and unsolved problems in female diseases, such as endometriosis, uterine cancer and female infertility, in a personalised manner. STUDY FUNDING/COMPETING INTEREST(S) This work is supported by funding from the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) to Y.J.K. (No. 2018R1C1B6003), to J.A. (No. 2020R1I1A1A01074136) and to H.S.K. (No. 2020R1C1C100787212). The authors report no conflicts of interest.

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Characteristics of the endometrium in menstruating species: lessons learned from the animal kingdom†

Cited by 20 publications

References 69 publications

Building a stem cell-based primate uterus

Building a stem cell-based primate uterus

Immunology and Immunotherapy of Endometriosis

Three-dimensional microengineered vascularised endometrium-on-a-chip

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