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 During the last decade the Toll like Receptors (TLR) were found to be a major part of innate immune system. Several reports have demonstrated the existence of TLRs in different tissues and organs. However, little has been done to identify TLRs in the FEMALE REPRODUCTIVE TRACT (FRT). In addition little information existed regarding variation in TLRs in FRT during the menstrual cycle and also the influences of sex hormones on TLRs expression and function in this tract. The distribution of TLR7-10 protein was detected by immunostaining in endometrium. Also RT-PCR was used to show the existence of TLR genes in human fallopian tube, endometrial tissue and OEE6/ E7 cells as a reliable model of fallopian tube epithelial cell. Q-PCR analysis was used to investigate relative expression of these genes during the menstrual cycle in human endometrium. In addition, separate and synergistic effects of sex hormones on TLRs were tested in OE-E6/E7 cells by using Q-PCR and ELISA. To confirm the specific effects of sex hormones in the study, antagonists against estradiol and progesterone were used. The results showed that TLR7-10 proteins were present in endometrial epithelium and stroma. TLR1-10 genes were expressed in human fallopian tube and endometrial tissue. The mean relative expression of TLR genes was significantly higher during the secretory phase of the menstrual cycle in endometrium. In addition, it was demonstrated that TLR 1-6 genes and proteins were expressed in OE-E6/E7 cell line. Our data clearly showed that Estrogen has no effect on the expression of TLRs except TLR1 in OE-E6/E7 cells. In contrast, progesterone had an inhibitory effect on the expression of TLR1-4 genes in this cell line. Moreover, we proved that the production of IL-6 was significantly increased in the presence of TLR3 ligand (poly (I: C)), and both sex hormones had a suppressive and biphasic effect on the production of IL-6 in the presence and absence of poly (I: C). Our results also suggested that the estrogen receptor b and nuclear progesterone receptor B are likely to mediate the hormonal regulation of TLR3 as these two receptors are the two main estrogen and progesterone receptors in OE-E6/E7.These results imply a potential variation in the expression and function of TLRs in FRT when different levels of sex hormones are present during different stages of the menstrual cycle. Clinically, Limited success in dealing with INFERTILITY issues and protection against sexually transmitted disease demonstrate the need for a greater understanding of the regulation of immune system in the FEMALE REPRODUCTIVE TRACT. Studying the function of TLRs in the FEMALE REPRODUCTIVE TRACT presents an exciting opportunity to further understand the regulation of innate immune system in the FEMALE REPRODUCTIVE TRACT. It seems sex hormones regulate the function and expression of TLRs in the FEMALE REPRODUCTIVE TRACT and therefore influence/regulate innate and adaptive immune function in this tract to protect against potential pathogens while providing an environment that supports an allogeneic foetus. How TLR function and expression is exactly regulated in reproductive tract by sex hormones would be a challenging but fruitful area of future research.


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