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Chip mimicking bovine endometrium utilized in research of things that may jeopardize being pregnant

Publicado em 07 junho 2021

To examine components that may jeopardize being pregnant success in cattle, researchers on the University of São Paulo (USP) in Brazil used a type of chip to imitate the setting of the endometrium, the tissue that traces the within of the uterus. 

The research was carried out by biologist Tiago Henrique Camara de Bem, a postdoctoral fellow on the University of São Paulo’s School of Animal Science and Food Engineering (FZEA-USP), in collaboration with 4 researchers on the University of Leeds within the UK. Their findings are reported in an article within the journal Endocrinology.

The researchers targeted on analyzing alterations in ranges of insulin and glucose in maternal epithelial and stromal cells, and the attainable penalties for preliminary improvement of the pregnancy. Epithelial cells are essentially the most exterior within the endometrium. They interface with the lumen and are in direct contact with the embryo. Stromal cells are additional inside, performing as help cells that information epithelial cell progress, differentiation and improvement, amongst different capabilities.

The group found that prime ranges of glucose altered 21 protein-encoding genes in epithelial cells and 191 in stromal cells, in addition to triggering quantitative modifications within the protein secretome (proteins secreted within the tradition medium, which on this case mimicked the endometrial fluid). “As we changed the amount of glucose and insulin in the culture medium, stressing the cells, we were able to switch genes on or off, determining whether they were or weren’t expressed,” Camara de Bem stated. 

Changes in insulin ranges altered the quantitative secretion of 196 proteins however resulted in restricted alteration of gene transcription. “The key factor may be the protein composition of the uterine fluid, in which these cells secrete protein into the embryo,” he defined. “We found this group of proteins to be associated with signaling pathways that play an important role in early pregnancy success in cattle, relating to metabolism, cellular matrix and other factors. All these discoveries evidence a mechanism whereby maternal glucose and insulin alterations can affect uterine functioning.”

Camara de Bem was supported by FAPESP by way of a postdoctoral fellowship for a mission carried out on the Molecular Morphophysiology and Development Laboratory underneath the supervision of Professor Flávio Vieira Meirelles, and a scholarship for a analysis internship overseas (BEPE). 


According to Camara de Bem, Brazil is a world chief within the manufacturing of bovine embryos, however however has a excessive fee of misplaced pregnancies. “A large proportion of our embryos are produced by in vitro fertilization. Oocytes are collected, matured, fertilized, cultured and transferred to synchronized recipients. However, 40% of pregnancies are lost in the third or fourth week,” he stated, recalling {that a} bovine being pregnant lasts about 9 months, as in people. 

Reproductive success is dependent upon a variety of situations. “Pregnancy is an interaction between the mother and the embryo that develops in the maternal uterus,” Camara de Bem stated. “It involves cross-talk between the embryo’s cells and the mother’s. This communication is influenced by multiple processes. Pregnancy loss can occur when the communication isn’t right—when the embryo can’t signal its presence or the mother doesn’t recognize the developing embryo.”

Stress because of environmental or dietary issues and even to the manufacturing course of itself can result in instability in maternal-embryo communication and disrupt the being pregnant, he continued. In the case of cattle, being pregnant in high-yield dairy cows is the principle downside, with the preliminary post-partum interval typically involving metabolic stress because of a unfavourable vitality stability within the dam.

“Glucose, for example, is a basic substrate for cell metabolism,” Camara de Bem stated. “Cells need glucose to perform their functions. Lactating cows undergo a metabolic challenge to produce milk. They consume a lot of energy because they need to maintain the basic functions of the organism as well as all the functions involved in milk production. The state of the mother’s metabolism significantly influences reproduction. Hence our focus on understanding the factors that cause metabolic stress in the environment that receives the embryo.” 

Endometrium on a chip

Camara de Bem burdened that the research was carried out in partnership with the group led by Niamh Forde, a professor on the University of Leeds Medical School and final creator of the article. “She’s investigating maternal recognition of pregnancy in cattle. I’m interested in investigating the signals sent by the embryo to the mother. We thought it would be a good collaboration and had this idea of developing an ‘endometrium on a chip’ that could be used for multicellular culture, i.e. growing more than one type of cell from the endometrium,” he stated. 

The chip resembles a histology slide, besides that it’s divided into chambers—compartments wherein the scientists seeded two varieties of cell. The partitions are made from a porous membrane that allows info to be exchanged between the 2 cell sorts cultured within the completely different chambers however doesn’t allow the cell sorts to modify positions. The gadget may be thought of a industrial chip tailored to simulate an endometrium. 

“Epithelial cells had been seeded within the higher chamber, stromal cells within the decrease,” Camara de Bem stated. “Both cell types are abundant in the endometrium. The upper chamber’s culture medium became enriched with factors produced and secreted by the epithelial cells, representing the endometrial secretome.”

The chip enabled the scientists to infuse the cells continually with a culture medium. “We cultured the cells for three days, injecting medium the whole time [one microliter per minute for 72 hours] with three different concentrations of glucose or two different concentrations of insulin,” he stated. “Nutrients were administered very slowly, in a flow mimicking the best medium physiology. This ensured that the cells were exposed to the same levels of glucose and insulin throughout the experiment.”


The technique was progressive and had by no means been used earlier than to imitate the bovine endometrium. Conventional cell tradition is just too easy to simulate all endometrial situations. “The endometrium is three-dimensional, with several types of cells and glands producing factors and nutrients to maintain the pregnancy,” Camara de Bem recalled. “In vitro embryo culture using the traditional method is static and involves a single cell type in an environment that doesn’t reflect the richness of the animal organism. You can grow cells, transfer embryos to a recipient and produce healthy animals, but we set out to recreate the process in a manner that was as close as possible to the physiological reality.” 

Camara de Bem famous that his companions on the University of Leeds are growing other forms of chip for embryo insertion. “The methodology opens up a wealth of opportunities, and in future we hope to be able to culture cells and embryos together in order to find out exactly what happens when there are changes in the medium and in communication with maternal cells. This is an opening for more applied research,” he stated.

The group’s work additionally provides a possible mannequin for the research of being pregnant in mammals, together with people. “Except for non-human primates, mice are the main model for studying humans. Placenta formation in mice is the most similar to the process in humans. On the other hand, unlike us mice have many offspring. In cattle, placentation is very different from what it is in humans, but the gestational period is similar and cows also have only one offspring per pregnancy. There will never be an ideal model, because of the differences between species, but this can be one more model,” he stated.

Breakthrough could lead to early detection of pregnancy complications

More info:
Tiago H C De Bem et al, Endometrium On-a-Chip Reveals Insulin- and Glucose-induced Alterations within the Transcriptome and Proteomic Secretome, Endocrinology (2021). DOI: 10.1210/endocr/bqab054

Chip mimicking bovine endometrium utilized in research of things that may jeopardize being pregnant (2021, June 7)
retrieved 7 June 2021

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