Long-term exposure to low doses of bisphenol S has hypoglycaemic effect in adult male mice by promoting insulin sensitivity and repressing gluconeogenesis

2021 ◽  
Vol 277 ◽  
pp. 116630
Author(s):  
Yajie Guo ◽  
Ziquan Lv ◽  
Zhi Tang ◽  
Suli Huang ◽  
Changfeng Peng ◽  
...  
2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Nicola Romano ◽  
Peter James Duncan ◽  
Oscar Nolan ◽  
Paul Roussel Le Tissier ◽  
Mike Shipston ◽  
...  

Abstract Glucocorticoids are prescribed for >3 months to 1% of the UK population. 10-50% of these long-term glucocorticoid treated patients develop persistent HPA axis suppression associated with mortality and morbidity. We have developed a mouse model of glucocorticoid-induced HPA axis dysfunction to determine the mechanisms resulting in persistent HPA axis suppression. Experiment 1: 36 C57BL/6 adult male mice received Dexamethasone (DEX,~10µg/day) or vehicle (CTL) via drinking water for 28 days, following which treatment was stopped and tissues were harvested at 0, 7 and 28 days. DEX suppressed waking serum corticosterone at days 0 and 7, recovering by day 28. Adrenal size remained lower 28 days following DEX withdrawal. DEX had no effect on whole pituitary pomc, nr3c1 or crhr1 expression, although avpr1b was increased at day 0. In the adrenal, hsd3b2 and cyp11a1 expression were reduced at time 0; normalising by 28 days. Experiment 2: 24 POMC-GFP male mice were treated as above. Tissues were collected at day 0 (n=6), 7 (n=3) and 10 (n=3) following withdrawal. Pooled corticotrophs (groups of 3) were isolated by FACS and RNA extracted for qPCR. DEX reduced corticotroph pomc expression at time 0 (x20 fold reduction), with x5 fold suppression at day 7, which recovered with evidence of compensation by day 10. DEX increased expression of avpr1b but not crhr1. CONCLUSION: 28 days dexamethasone treatment in mice suppresses the HPA axis. HPA suppression is evident 7 days following withdrawal of dexamethasone in the adrenal, corticotroph population and corticosterone production. Further analysis will determine mechanisms for delays in HPA axis recovery.


2016 ◽  
Vol 18 (9) ◽  
Author(s):  
Mahnaz Kesmati ◽  
Zeinab Sargholi Notarki ◽  
Narges Issapareh ◽  
Mozhgan Torabi

2020 ◽  
Author(s):  
Hedvika Řimnáčová ◽  
Miriam Štiavnická ◽  
Jiří Moravec ◽  
Marouane Chemek ◽  
Yaroslav Kolinko ◽  
...  

Abstract Background: Bisphenol S (BPS) is increasingly used as a replacement for bisphenol A in the manufacture of products containing polycarbonates and epoxy resins. However, further studies of BPS exposure are needed for the assessment of health risks to humans. In this study we assessed the potential harmfulness of low-dose BPS on reproduction in male mice.Methods: To simulate human exposure under experimental conditions, 8-week-old outbred ICR male mice received 8 weeks of drinking water containing a broad range of BPS doses [0.001, 1.0, or 100 µg/kg body weight (bw)/day, BPS1-3] or vehicle control. Mice were sacrificed and testicular tissue taken for histological analysis and protein identification by nano-liquid chromatography/mass spectrometry (MS) and sperm collected for immunodetection of acetylated lysine and phosphorylated tyrosine followed by protein characterisation using matrix-assisted laser desorption ionisation time-of-flight MS (MALDI-TOF MS).Results: The results indicate that compared to vehicle, 100 µg/kg/day exposure (BPS3) leads to 1) significant histopathology in testicular tissue; and, 2) higher levels of the histone protein γH2AX, a reliable marker of DNA damage. There were fewer mature spermatozoa in the germ layer in the experimental group treated with 1 µg/kg bw (BPS2). Finally, western blot and MALDI-TOF MS studies showed significant alterations in the sperm acetylome and phosphorylome in mice treated with the lowest exposure (0.001 µg/kg/day; BPS1), although the dose is several times lower than what has been published so far. Conclusions: In summary, this range of qualitative and quantitative findings in young male mice raise the possibility that very low doses of BPS may impair mammalian reproduction through epigenetic modifications of sperm proteins.


Chemosphere ◽  
2019 ◽  
Vol 221 ◽  
pp. 500-510 ◽  
Author(s):  
Weiwei Wang ◽  
Xiaona Zhang ◽  
Jingyu Qin ◽  
Penghao Wei ◽  
Yi Jia ◽  
...  

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Hedvika Řimnáčová ◽  
Miriam Štiavnická ◽  
Jiří Moravec ◽  
Marouane Chemek ◽  
Yaroslav Kolinko ◽  
...  

Reproduction ◽  
2018 ◽  
Vol 156 (1) ◽  
pp. 47-57 ◽  
Author(s):  
Jan Nevoral ◽  
Yaroslav Kolinko ◽  
Jiří Moravec ◽  
Tereza Žalmanová ◽  
Kristýna Hošková ◽  
...  

Bisphenols belong to the endocrine disruptors, affecting reproduction even in extremely low doses. Bisphenol S (BPS) has become widely used as a substitute for the earlier-used bisphenol A; however, its harmlessness is questionable. The aim of this study was to evaluate the effect of BPS on folliculogenesis and oocyte quality afterin vivoexposure to low doses of BPS. Four-week-old ICR females (n = 16 in each experimental group) were exposed to vehicle control (VC), BPS1 (0.001 ng BPS.g/bw/day), BPS2 (0.1 ng.g/bw/day), BPS3 (10 ng.g/bw/day) and BPS4 (100 ng.g/bw/day) for 4 weeks. Ovaries were subjected to stereology and nano liquid chromatography-mass spectrometry (LC/MS). Simultaneously, metaphase II oocytes were obtained after pregnant mare serum gonadotrophin and human chorionic gonadotrophin administration, followed by immunostaining. In particular, mating and two-cell embryo flushing were performed. We observed that BPS decreases the amount of ovarian follicles and BPS2 (0.1 ng.g/bw/day) affects the volume of antral follicles. Accordingly, ovarian proteome is affected after BPS2 treatment. While BPS2 dosing results mainly in cytoskeletal damage in matured oocytes, the effects of BPS3 and BPS4 seem to be due instead to epigenetic alterations in oocytes. Arguably, these changes lead to observed affection ofin vivofertilization rate after BPS3 and BPS4 treatment. BPS significantly affects female reproduction astoundingly in extremely low doses. These findings underline the necessity to assess the risk of ongoing BPS exposure for public health.


2016 ◽  
Vol 97 (4) ◽  
pp. 310-316 ◽  
Author(s):  
Viviane P. Santana ◽  
Évila S. Salles ◽  
Deborah E. Correa ◽  
Bianca F. Gonçalves ◽  
Silvana G. Campos ◽  
...  

2020 ◽  
Author(s):  
Hedvika Řimnáčová ◽  
Miriam Štiavnická ◽  
Jiří Moravec ◽  
Marouane Chemek ◽  
Yaroslav Kolinko ◽  
...  

Abstract Background: Bisphenol S (BPS) is increasingly used as a replacement for bisphenol A in the manufacture of products containing polycarbonates and epoxy resins. However, further studies of BPS exposure are needed for the assessment of health risks to humans. In this study we assessed the potential harmfulness of low-dose BPS on reproduction in male mice.Methods: To simulate human exposure under experimental conditions, 8-week-old outbred ICR male mice received 8 weeks of drinking water containing a broad range of BPS doses [0.001, 1.0, or 100 µg/kg body weight (bw)/day, BPS1-3] or vehicle control. Mice were sacrificed and testicular tissue taken for histological analysis and protein identification by nano-liquid chromatography/mass spectrometry (MS) and sperm collected for immunodetection of acetylated lysine and phosphorylated tyrosine followed by protein characterisation using matrix-assisted laser desorption ionisation time-of-flight MS (MALDI-TOF MS).Results: The results indicate that compared to vehicle, 100 µg/kg/day exposure (BPS3) leads to 1) significant histopathology in testicular tissue; and, 2) higher levels of the histone protein γH2AX, a reliable marker of DNA damage. There were fewer mature spermatozoa in the germ layer in the experimental group treated with 1 µg/kg bw (BPS2). Finally, Western blot and MALDI-TOF MS studies showed significant alterations in the sperm acetylome and phosphorylome in mice treated with the lowest (BPS1) exposure (0.001 µg/kg/day).Conclusions: In summary, this range of qualitative and quantitative findings in young male mice raise the possibility that relatively low doses of BPS may impair mammalian reproduction through epigenetic modifications of sperm proteins.


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