Obiekt
Tytuł: Studies on the distribution and role of interstitial cells of the Cajal type (telocytes) in the fallopian tubes as a potential factor of infertility in women
Abstrakt:
Infertility, affecting a huge group of the female population, is one of the problems of modern medicine. Etiopathogenesis involves many exo- and endogenous factors, and doesn’t always allow for causal treatment. In recent years, the understanding of smooth muscle physiology has changed thanks to research on a population of interstitial cells called telocytes. It has been proven that telocytes participate in local transmission of signals, e.g. to nearby neurons or myocytes. The presence of uterine fibroids negatively affects fertility. Analyzing literature, it has been noted that patients with even small (<1.5 cm) uterine fibroids have reduced fertility, and about 20% of them suffer from infertility. Moreover, removing these fibroids increased the pregnancy rate by up to 16%- 70%. Interestingly, this relation was observed not only for submucosal miomas, associated with fertility disorders through their direct proximity to the endometrium – the target implantation site - is obvious, but also in the case of intramural fibroids, whose relationship to infertility remains unclear. The aim of the project was to determine the distribution and role of telocytes in the fallopian tubes and their involvement in processes leading to abnormalities that may result in infertility. A total of 74 women after hysterectomy participated in the study, which constituted the study and the control grou ; p. The material constituted archival paraffin cubes and fragments of tissues collected during routinely performed gynecological procedures. Routine histopathological analysis was performed -hematoxylin-eosin and Masson's trichrome staining. Then, immunohistochemical tests were taken in the collected specimens to assess the expression of cell markers: c-Kit and mast cell tryptase, CD34 and PDGFRα, PGP9.5, followed by immunohistochemical assays by double and triple staining to show co-expression or lack of for these and other markers: c-Kit and mast cell tryptase, ANO-1, CD34, CD31, PDGFRII-α, PGP9.5, iNOS, ChAT, sFlt-1 and estrogen and progesterone receptors. The respective groups were compared and the results presented in details in the publications constituting the doctoral dissertation. Publication No. 1-compared tissues from a group of operated patients with and without fibroids, which were analyzed for differences in histopathological structure, the expression of estrogen and progesterone receptors and the number of telocytes. Observed a significant decrease in the density of telocytes in the leiomyomas themselves and smaller in the surrounding myometrium in the group of patients with fibroids. In addition showed a decrease in the expression of the estrogen receptor - both in the muscle of adjacent tissue and in the myoma, and an increase in the expression of the progestero ; ne receptor – in myoma. Telocytes were present mainly near to the vessels. Collected data allowed to draw conclusions about the potential role of telocytes in maintaining local homeostasis i proper functioning of organs responsible for fertilization, transport and implantation of a fertilized egg. In paper No.2, we showed that telocytes, in the oviducts, are present near the vessels, and in patients with uterine fibroids - there are more of them (TC) comparing to the control group. We observed PGP 9.5 positive nerve fibers penetrating spaces between smooth muscle cells, in close proximity to the telocytes and beyond lamina propria we found ChAT positive nerve fibers, which also were in close proximity to blood vessels and telocytes, similarly iNOS positive structures were located. Examination revealed double-marked foci iNOS, ChAT, PGP 9.5 positive and CD34 positive, confirming interactions between nerves, endothelial cells, smooth muscle cells and telocytes in the fallopian tubes. We also assessed the expression of estrogen and progesterone receptors of telocytes by double immunolabeling with CD34(+) marker. We observed higher expression of progesterone receptors and lower expression of estrogen receptors in the telocytes of fallopian tubes from a group of patients with uterine fibroids. These results confirmed observations and hypotheses from our first paper, where similar im ; ages were seen in cases of uterine myoma. Telocytes were also found near the blood vessels. In addition, tubal telocytes were highly expressed low-conductivity calcium-activated potassium channels (SK3) in both study groups. Performing subsequent labeling, we noticed a lower expression of HIF-1 in patients in the group with uterine fibroids compared to the control group. In the next paper (No. 3) we compared the expression of HIF-1, HO, VEGF and VEGFR, NOS, estrogen and progesterone receptors in the fallopian tubes obtained from patients with and without fibroids (which constituted the control group). Tubal and myometrial telocytes were also compared in both these groups. In addition, a biochemical analysis was performed for the levels of FSH, LH, AMH, sFlt, estrogen and progesterone in blood samples taken from patients. We found that the fallopian tubes of patients with uterine fibroids have a different expression of steroid receptors - less estrogen and more progesterone, and a reduced number of telocytes; they also show decreased VEFG expression and increased HIF-1 expression. Blood analyzes showed higher level of progesterone and lower level of AMH in the patients with uterine fibroids; at the same time, no differences were found in levels of sFlt, FSH and LH in the blond samples. Paper No. 4 describes extremely rare case of ovarian pregnancy on the same side after tubal on ; e. This case was analyzed for pathology of the oviduct and the relation with telocytes in aspect of tubal motility disorders. Samples from the fallopian tube of a patient with an ectopic pregnancy showed the presence of telocytes in in the vicinity of vessels, muscle and nerve cells. Telocytes were present mainly near blood vessels, nerve cells and within the muscularis layer of the fallopian tube. Greater expression of PGP-positive fibers, especially, was observed in the muscle layer in a patient with ectopic pregnancy, and in the control group a larger one positive NOS expression. The close proximity of telocytes and PGP and iNOS positives nerve fibers suggest that they may be directly involved in the process of neurotransmission and the presence of estrogen and progesterone receptors in telocytes suggests their dependence on hormonal fluctuations occurring in a woman's cycle. Summarizing the most important results of our research: 1. The presence of fibroids in the uterus can cause morphological and functional changes in the fallopian tube. 2. In the fallopian tubes of women with uterine fibroids, an increase in the number of telocytes was observed and changes in the expression of estrogen and progesterone receptors. 3. Changes in the expression of proangiogenic factors were found: increased expression of HIF-1, decrease in VEGF, VEGFR, HO and iNOS in the fallopian tubes of ; patients with uterine fibroids. 4. Changing the amount of telocytes as well as their environment directly affects motility of cilia, motility of the fallopian tube, which may be the cause of abnormal embryo implantation in the fallopian tube, disorders of the regulation of apoptosis processes, angiogenesis and contribute to the development of fibrosis. 5. Close interaction of telocytes and nerve cells, PGP and iNOS positive nerve fibres indicates their potential involvement in local signals transmission between cells and influence on the motility of the muscularis of the fallopian tube.
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Instytucja nadająca tytuł:
Rada Dyscypliny Nauki medyczne
Promotor:
Gil, Krzysztof ; Bereza, Tomasz
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Data ostatniej modyfikacji:
24 paź 2024
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24 paź 2024
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| Nazwa wydania | Data |
|---|---|
| ZB-140540 | 24 paź 2024 |
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