Tetrachlorobisphenol A (TCBPA) is used as flame retardant, and it has been widely detected in the environmental and human samples. TCBPA is an endocrine disrupting chemical, but its effects on the immune system remains poorly understood. Here the effects of TCBPA on immune system were studied using combined in vivo and in vitro assays. Results showed that TCBPA could suppress the immune response in BALB/c mice via reducing the ratio of CD3 + T lymphocytes to regulatory T cells. Moreover, TCBPA exposure significantly induced the increasing secretion of four pro-inflammatory cytokines (IL-2, IL-12, IFN-γ, and TNF-α) and four anti-inflammatory cytokines (IL-4, IL-5, IL-10, GM-CSF) in mice serum. Interestingly, uterine edema was observed in over 80% TCBPA-treated mice after 14- day exposure. TCBPA was detected in 18.6% serum samples of 150 female volunteers in this study. Therefore, our findings provided evidence that TCBPA exposure may cause adverse outcomes on immune system and uterus, suggesting that environmental exposure of TCBPA, as well as its adverse effects on human health should be of concern.
Tetrabromobisphenol A (TBBPA) is a widely used flame retardant , but the adverse outcomes induced by TBBPA has not been fully elucidated. In this study, TBBPA was detected in 54.9% of 102 female Chinese volunteers with an average serum concentration of 0.34 ng/mL. To investigate whether TBBPA induces adverse outcomes at environmentally relevant exposure doses, the mice were exposed to TBBPA for 14 and 28 days. The internal doses of TBBPA in mice serum were nearly the internal doses in volunteers. TBBPA significantly increased the secretion of some pro-inflammatory cytokines and suppressed immune responses in mice under such serum concentrations after 14- and 28-days exposure. Interestingly, uterine edema was observed in TBBPA-treated mice. In primary uterine cells model, the results showed TBBPA exposure suppressed THRβ expression, leading to the activation of the inflammatory PI3K/NF-κB signaling pathway. Our findings indicated that the uterus is the susceptible target organ of TBBPA and TBBPA exposure might increase risk of uterine cancer through deregulating inflammation pathways.
Jinlong Qin,Min Sun,Jiajing Cheng,Huici Jiang,Mingchen Lv,Jianxing Jing,Ran Chen,Zhen Fan,Jianzhong Du
Unavoidable damage to the basal layer of the endometrium has a huge negative impact on a woman’s reproductive health and menstrual cycle. However, it is difficult for medicine to penetrate a series of biological barriers toward the basal layer in the deeper area of the endometrium. To meet this challenge, we developed an ultrasound-responsive hydrogel incorporated with a transforming growth factor-beta (TGF-β) mimetic peptide to enhance pregnancy outcomes by restoring the function of a wounded endometrium due to its deep-tissue-penetration capability. In vitro studies revealed that the TGF-β-mimetic-peptide-loaded hydrogel could achieve 64.35% of cell migration under ultrasound stimulation even in phosphate-buffered saline of pH 6.0. Upon in situ sonication at the uterus, carboxymethyl chitosan can be released from degraded hydrogel to open tight junctions with reduced interstitial pressure by ultrasound to promote deep penetration. Rat studies revealed that the penetration capability of TGF-β-mimetic-peptide-loaded hydrogel with sonication was 1.6 times higher than that of the control group. Besides the rat uterine model, ex vivo human uterine tissue was also collected and imaged, demonstrating up to ∼700 μm of tissue penetration depth. In addition, compared to control groups, effective uterus recovery without intrauterine stenosis and endometrial cavity fluid was observed from rats with severe uterine injury treated by TGF-β-mimetic-peptide-loaded hydrogel. In addition, fertility restoration in the endometrial injury model was observed after treatment with such an ultrasound-responsive hydrogel incorporated with TGF-β mimetic peptides. Overall, this work provides an effective approach to treating endometrial injury for enhanced pregnancy outcomes.
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