Oviductal Telocytes in Patients with Uterine Myoma

Tubal factor infertility occurs in 30–35% of infertile pairs and may be caused by impaired muscular contractility and ciliary beating as well as immunological imbalance and chronic inflammation. Newly discovered telocytes (TCs) have a wide palette of features, which play a role in oviduct physiology. We have observed tissue samples from human fallopian tubes in patients with and without uterine myoma by immunolabelling. According to the immunohistochemical co-expression of markers, it has been determined that TCs are engaged in a wide range of physiological processes, including local innervation, sensitivity to hypoxia, regulation of calcium, and sex steroid hormones balances. Due to the proximity of NOS- and ChAT-positive nerve fibers and the expression of ion channels markers, tubal TCs might be considered conductor cells. Additionally, their integration in contractions and cilia physiology in the context of fertility has been revealed. We have observed the difference in telocytes expression in the human oviduct between groups of patients and attempted to describe this population of cells specifically in the case of infertility development, a clinically relevant avenue for further studies.

Toll-Like Receptor 3 Deficiency Leads to Altered Immune Responses to Chlamydia trachomatis Infection in Human Oviduct Epithelial Cells

ABSTRACT Reproductive tract pathology caused by Chlamydia trachomatis infection is an important global cause of human infertility. To better understand the mechanisms associated with Chlamydia-induced genital tract pathogenesis in humans, we used CRISPR genome editing to disrupt Toll-like receptor 3 (TLR3) function in the human oviduct epithelial (hOE) cell line OE-E6/E7 in order to investigate the possible role(s) of TLR3 signaling in the immune response to Chlamydia. Disruption of TLR3 function in these cells significantly diminished the Chlamydia-induced synthesis of several inflammation biomarkers, including interferon beta (IFN-β), interleukin-6 (IL-6), interleukin-6 receptor alpha (IL-6Rα), soluble interleukin-6 receptor beta (sIL-6Rβ, or gp130), IL-8, IL-20, IL-26, IL-34, soluble tumor necrosis factor receptor 1 (sTNF-R1), tumor necrosis factor ligand superfamily member 13B (TNFSF13B), matrix metalloproteinase 1 (MMP-1), MMP-2, and MMP-3. In contrast, the Chlamydia-induced synthesis of CCL5, IL-29 (IFN-λ1), and IL-28A (IFN-λ2) was significantly increased in TLR3-deficient hOE cells compared to their wild-type counterparts. Our results indicate a role for TLR3 signaling in limiting the genital tract fibrosis, scarring, and chronic inflammation often associated with human chlamydial disease. Interestingly, we saw that Chlamydia infection induced the production of biomarkers associated with persistence, tumor metastasis, and autoimmunity, such as soluble CD163 (sCD163), chitinase-3-like protein 1, osteopontin, and pentraxin-3, in hOE cells; however, their expression levels were significantly dysregulated in TLR3-deficient hOE cells. Finally, we demonstrate using hOE cells that TLR3 deficiency resulted in an increased amount of chlamydial lipopolysaccharide (LPS) within Chlamydia inclusions, which is suggestive that TLR3 deficiency leads to enhanced chlamydial replication and possibly increased genital tract pathogenesis during human infection.

TLR3 Deficiency Leads to Altered Immune Responses toChlamydia trachomatisInfection in Human Oviduct Epithelial Cells

ABSTRACTReproductive tract pathology caused byChlamydia trachomatisinfection is an important global cause of human infertility. To better understand the mechanisms associated withChlamydia-induced genital tract pathogenesis in humans, we used CRISPR genome editing to disrupt TLR3 function in the human oviduct epithelial (hOE) cell-line OE-E6/E7, in order to investigate the possible role(s) of TLR3 signaling in the immune response toChlamydia. Disruption of TLR3 function in these cells significantly diminished theChlamydia-induced synthesis of several inflammation biomarkers including IFN-β, IL-6, IL-6Ra, sIL-6Rβ (gp130), IL-8, IL-20, IL-26, IL-34, sTNF-R1, TNFSF13B, MMP-1, MMP-2, and MMP-3. In contrast, theChlamydia-induced synthesis of CCL-5, IL-29 (IFNλ1) and IL-28A (IFNλ2) were significantlyincreasedin the TLR3-deficient hOE cells when compared to their wild-type counterparts. Our results propose a role for TLR3 signaling in limiting the genital tract fibrosis, scarring, and chronic inflammation often associated with human chlamydial disease. Interestingly, we saw thatChlamydiainfection induced the production of biomarkers associated with persistence, tumor metastasis, and autoimmunity such as soluble CD163 (sCD163), chitinase-3-like protein 1, osteopontin, and pentraxin-3 in the hOE cells; however, their expression levels were significantly dysregulated in the TLR3-deficient hOE cells. Finally, we demonstrate using the hOE cells that TLR3 deficiency resulted in an increased amount of chlamydial LPS within theChlamydiainclusion, which is suggestive that TLR3 deficiency leads to enhanced chlamydial replication and possibly increased genital tract pathogenesis during human infection.AbbreviationshOE, human OE-E6/E7 cells; TLR3 KO, TLR3 knockout cell line; poly (I:C), Polyinosinic–polycytidylic acid sodium salt.