Toll-Like Receptor 4 Inhibits Estradiol Secretion via NF-κB Signaling in Human Granulosa Cells

Guan, Haiyun; Xia, He-Xia; Chen, Xiuying; Wang, Lu; Tang, Zhijing; Zhang, Wei

doi:10.3389/fendo.2021.629554

Cited by 15 publications

(5 citation statements)

References 28 publications

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“…12 TLR4 recruits p38 signaling and SB203580 (a p38 inhibitor) reduces the LPS-induced expression of IL-1 and TNF-α. 56,59 In accordance with previous research, we found that TLR4 and its downstream p38MAPK may potentially contribute to the generation of PIPN. Elimination of gut microbiota by broad-spectrum antibiotics significantly enhanced the activity of the TLR4/p38 signaling pathway in response to LPS, while FMT from Vehicle rats reduced the TLR4/p38 signaling activity induced by intrathecal injections of TAK242 and SB203580.…”

Section: Discussionsupporting

confidence: 92%

Fecal Microbiota Transplantation Alleviated Paclitaxel-Induced Peripheral Neuropathy by Interfering with Astrocytes and TLR4/p38MAPK Pathway in Rats

Shi,

Chen,

Zheng

et al. 2023

JPR

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Paclitaxel-induced peripheral neuropathy (PIPN) constitutes a refractory and progressive adverse consequence of paclitaxel treatment, causing pain and sensory anomalies in cancer survivors. Although the gut-brain axis is involved in multiple disorders including cancer, its impact on peripheral pain conditions remains elusive. Thus, we assessed the importance of gut microbiota and related mechanisms in PIPN. Methods: By implementing fecal microbiota transplantation (FMT) in a rat PIPN model (ie, rats treated with paclitaxel; hereafter as PIPN rats), we explored the effect of gut microbiota on PIPN rats using multiple methods, including different behavioral tests, 16S ribosomal DNA (rDNA) sequencing, and biochemical techniques. Results: Sequencing of 16S rDNA revealed that the abundance of genera Bacteroides and UCG-005 increased, while that of genera Turicibacter, Clostridium sensu stricto 1 and Corynebacterium decreased in the PIPN rats. However, when treated with FMT using fecal from normal rats, the mechanical allodynia and thermal hyperalgesia in PIPN rats were significantly alleviated. In addition, FMT treatment reduced the expression of toll-like receptor 4 (TLR4), phospho-p38 mitogen-activated protein kinase (p-p38MAPK), and the astrocytic marker glial fibrillary acidic protein in the colon and spinal dorsal horn. TAK242 (a TLR4 inhibitor) significantly alleviated the behavioral hypersensitivity of PIPN rats and inhibited the TLR4/p38MAPK pathway in astrocytes in these rats. Conclusion:The gut microbiota played a critical role in PIPN. Future therapies treating PIPN should consider microbe-based treatment as an option.

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Section: Discussionsupporting

confidence: 92%

Fecal Microbiota Transplantation Alleviated Paclitaxel-Induced Peripheral Neuropathy by Interfering with Astrocytes and TLR4/p38MAPK Pathway in Rats

Shi,

Chen,

Zheng

et al. 2023

JPR

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“…Previous research has shown that LPS can disturb the primordial follicle pool, promote primordial follicle development, and accelerate follicular atresia (5). Some studies showed that LPS activated the NF-κB signal pathway, then inhibited the secretion of estrogen in mouse granulosa cells, and further decreased antral follicles and ovulation (18). LPS at high levels in the follicular fluid inhibited steroid production, further affecting dominant follicle development (19,20).…”

Section: Discussionmentioning

confidence: 99%

Mild infection induced by low-dose LPS does not impair follicular development and is beneficial to pregnancy in mice

Zeng²,

Li³

et al. 2023

Front. Vet. Sci.

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The reproductive tract is susceptible to infection by a variety of bacteria, which can impair ovarian and uterine function. However, there is little known about whether mild infection can harm follicle development and embryo implantation. Here our results showed that the immune response to a mild infection simulated by low-dose LPS induced inflammatory factor IL-1b expression and decreased MMP2 expression involved in embryo implantation. LPS treatment also inhibited the ovulation process and reduced litter weight. Despite the immune response and the disturbed ovulation induced by treatment with low-dose LPS, the overall result was beneficial to mouse pregnancy. This research provides the necessary foundation for exploring the effects of mild bacterial infection on ovarian and uterine function in mammals.

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“…LPS significantly decreased the cell proliferation in the glandular epithelium, luminal epithelium, and stroma in the uterus during the preimplantation period ( Deb et al, 2005 ). Moreover, it has been shown that LPS affects uterine function by binding to TLR4 expressed in endometrial cells ( Sheldon & Roberts, 2010 ) and that LPS-induced TLR4 activation in the ovary inhibits E2 secretion, resulting in uterine collapse ( Guan et al, 2021 ). On the other hand, LPS stimulates immune cells such as T cells and macrophages in mice to produce cytokines that affect the uterus and ovaries ( Agostinis et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Lipid Polysaccharides have a Detrimental Effect on the Function of the Ovaries and Uterus in Mice through Increased Pro-Inflammatory Cytokines

Seo¹,

Lee²,

Kim³

et al. 2022

Dev. Reprod.

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As the number of coronavirus disease 2019 (COVID-19) vaccinations increases, various side effects are being reported, and menstrual abnormalities have been reported as a side effect in women. However, it is still unclear whether the COVID-19 vaccine has detrimental effects on the female reproductive system. Therefore, we investigated the effect of excessive immune response on reproductive function by administering Lipopolysaccharides (LPS) instead of the COVID-19 vaccine. The immune response in mice was induced by injection of LPS. Mice injected with saline 5 times were used as a control group, and mice injected with LPS 5 times were used as an experimental group. Repeated administration of LPS significantly reduced the number of corpus luteum (CL). On the other hand, the injection of LPS did not affect the development of follicles leading before the CL. The expression of the apoptosis-related genes Fas and Fas-L increased in the experimental group. In addition, the expression of the inflammation-related genes increased in the experimental group. In this study, we confirmed that LPS had detrimental effects on the uterus and ovaries in mice. These results suggest that injection of LPS can cause immune reactions within the uterus and ovaries and cause hormonal changes, which can have adverse effects such as abnormal operation or bleeding of the menstrual cycle. These results are expected to help determine the cause of decreased reproductive function, infertility, or physiological disorders caused by the COVID-19 vaccine.

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Toll-Like Receptor 4 Inhibits Estradiol Secretion via NF-κB Signaling in Human Granulosa Cells

Cited by 15 publications

References 28 publications

Fecal Microbiota Transplantation Alleviated Paclitaxel-Induced Peripheral Neuropathy by Interfering with Astrocytes and TLR4/p38MAPK Pathway in Rats

Fecal Microbiota Transplantation Alleviated Paclitaxel-Induced Peripheral Neuropathy by Interfering with Astrocytes and TLR4/p38MAPK Pathway in Rats

Mild infection induced by low-dose LPS does not impair follicular development and is beneficial to pregnancy in mice

Lipid Polysaccharides have a Detrimental Effect on the Function of the Ovaries and Uterus in Mice through Increased Pro-Inflammatory Cytokines

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