Firstly, we needed to adapt the tubal organoid model to our specific needs, to allow for both infection with CT and unhindered interaction with other types of cells introduced into the model. This modification enabled us to examine the effect CT infection has on the tubal surface. As a result, we were able to detect changes to the ‘normal’ microenvironment in the tube induced by CT, resulting in different levels of inflammation and disruptions to its physiological function.
Secondly, we conducted a comparison of our earlier research findings on CT-caused tubal pathology with the host group’s data in order to seek most promising and most reliable gene and SNP candidates. The key strength of our previous findings is the fact that they were obtained by studying 2500 samples from female patients diagnosed with CT infection and/or tubal pathology. Thanks to the opportunity to collaborate with the host group, we were able to compare our data with their analyses of the activity of genes in the infected tubal organoid model. As a result, we produced a list of 15 gene variants (within 12 genes) that we wanted to continue focusing on in our project.
Our main emphasis was on a gene for a particular chemical signal molecule secreted in the tube, particularly in the presence of an ongoing tubal CT infection. We tested the effect of SNPs from several different genes known to interact with this factor. Based on our findings, we were able to conclude that the production of the factor in our CT-infected organoid model depends on the presence or absence of individual studied SNPs. We detected that its production is higher if a particular SNP variant is present in at least one gene copy. Furthermore, we observed that active acute CT infection alters the presence of several proteins on the inner surface of the Fallopian tube. These observations suggest that CT infection may likely change the inflammatory conditions in the Fallopian tube and promote tubal pathology, depending on a woman’s genetic profile.
Finally, knowledge and skills gathered in this project are to be used in developing new modified study models for tubal complications. Experience from building our model can be applied in the process of developing models of other organs, or models for studying other infections.
