scholarly journals Low Dose of Genistein Alleviates Mono-(2-Ethylhexyl) Phthalate-Induced Fetal Testis Disorder Based on Organ Culture Model

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Tong-Dian Zhang ◽  
Yu-Bo Ma ◽  
He-Cheng Li ◽  
Tie Chong ◽  
Zi-Ming Wang ◽  
...  

Mono-(2-ethylhexyl) phthalate (MEHP) and genistein have been classified as endocrine-disrupting chemicals (EDCs) which interfere with the differentiation and development of the male reproductive system. However, how these two EDCs would affect fetal rat testis development at a low dose was rarely studied. In this study, we established the organ culture system and applied it to evaluate testicular effects following multiple EDC exposure at a low dose. 15.5 days postcoitum fetal rat testes were dissected, cultured, and exposed to vehicle (control), GEN (1 μmol/L, G), MEHP (1 μmol/L, M), or GEN (1 μmol/L)+MEHP (1 μmol/L, G+M). Testicular cell markers, testosterone concentration, redox state, testicular histology, and testicular ultrastructure were evaluated. Our results showed that a low dose of MEHP suppressed the development of Sertoli cells, Leydig cells, and gonocytes by triggering oxidative injuries, which was consistent with the ultrastructural findings. However, coadministration of genistein at a low dose could partially attenuate MEHP-induced fetal testis damage through antioxidative action. Cotreatment of genistein at a low dose may have a promising future on its protecting role for attenuating other EDC-induced reproductive disorders during early life. Based on the results, it can be speculated that dietary intake of isoflavones may make the fetal testis less susceptible to phthalate-induced injury.

2013 ◽  
Vol 765-767 ◽  
pp. 2944-2948 ◽  
Author(s):  
Xiao Ling Shao ◽  
Wen Qi Zhong ◽  
Xiao Yan Ma ◽  
Ang Gao ◽  
Xiang Yang Wu ◽  
...  

Yeast two-hybrid system was used to investigate the estrogenic activities of 13 kinds of representative endocrine disrupting chemicals (EDCs) and their combinary effects. Results show that the order of estrogenic potencies for these chemicals is: 17α-ethynylestradiol>diethylstilbestrol >17β-estradiol>estrone>estriol>branchedp-nonylphenol>4-t-octylphenol>bisphenol A>diethyl phthalate>4-n-nonylphenol>di-(2-ethylhexyl) phthalate>dibutyl phthalate>dimethyl phthalate. The mixture effects of multiple EDCs were compared to those obtained from individual chemicals, using the model of concentration addition. Results reveal that the estrogenicities of multicomponent mixtures of more than three (including three) of EDCs follow antagonistic effects, while there is no definite conclusion for binary systems. The less than additive effects were also confirmed in the spiked experiments conducted in the extracts of real water samples.


2021 ◽  
Author(s):  
Fabrizia Carli ◽  
Demetrio Ciociaro ◽  
Amalia Gastaldelli

AbstractExposomics analyses have highlighted the importance of biomonitoring of human exposure to pollutants, even non-persistent, for the prevention of non-communicable diseases like obesity, diabetes, non-alcoholic fatty liver disease, atherosclerosis and cardiovascular diseases. Phthalates and bisphenol A (BPA) are endocrine disrupting chemicals (EDCs) widely used in industry and in a large range of daily life products that increase the risk of endocrine and cardiometabolic diseases especially if the exposure starts during childhood. Thus, it is important the biomonitoring of exposure to these compounds not only in adulthood but also in childhood. This was the goal of the LIFE-PERSUADED project that measured the exposure to phthalates (DEHP metabolites, MEHP, MEHHP, MEOHP) and BPA in Italian mother-children couples of different ages. In this paper we describe the method that was set up for the LIFE PERSUADED project and validated during in the proficiency test (ICI/EQUAS) showing that accurate determination of urinary phthalates and BPA can be achieved starting from small sample size (0.5ml) using two MS techniques applied in cascade on the same deconjugated matrix.


2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Qianqian Tang ◽  
Bingli Lei ◽  
Yun Liu ◽  
Xiaolan Zhang ◽  
Qian Liu ◽  
...  

Typical environmental endocrine-disrupting chemicals (EDCs) such as estradiol valerate (EV), diethylstilbestrol (DES), di-2-ethylhexyl phthalate (DEHP), mono-2-ethylhexyl phthalate (MEHP), and bisphenol A (BPA) have a strong reproductive and developmental toxicity at low concentrations. However, information on their joint toxicity is scarce. In this study, we evaluated the combined effects of EV and other four EDCs (DES, DEHP, MEHP, and BPA) on the human breast MCF-7 cells by detecting the cell proliferation, intracellular reactive oxygen species (ROS) levels, and estrogen receptor alpha (ERα) protein expression using equal concentration ratio method. The results showed that, after exposure for 24, 48, and 72 h, single EV, DES, and BPA can promote the proliferation of MCF-7 human breast cancer cells, and EV has the strongest effect in inducing cell proliferation. DEHP and MEHP cannot induce MCF-7 cell proliferation for all exposure time, while cell proliferation induced by EV was significantly attenuated by DES, BPA, DEHP, and MEHP when they mixed with EV. For intracellular ROS, single EV, BPA, DES, DEHP, and MEHP elevated intracellular ROS levels for different exposure time. Similar to the cell proliferation, DES and BPA decreased intracellular ROS levels induced by EV when they mixed with EV for 24 h. EV, DES, and BPA exposed alone or combined with EV upregulated the ERα protein expression. However, DEHP and MEHP exposed alone or combined with EV had no effect on ERα protein expression, indicating that DEHP or MEHP could attenuate ERα protein expression upregulated by EV. These results showed that the joint toxicity of binary mixtures of EV and other EDCs do not interact in a synergistic fashion in inducing cell proliferation, intracellular ROS levels, and ERα protein expression. These findings have important implications in the human risk assessments of EV mixed with other EDCs in the environment.


2002 ◽  
Vol 3 (5) ◽  
pp. 551-557 ◽  
Author(s):  
Yukako Yoshikawa ◽  
Ayako Hayashi ◽  
Maya Inai ◽  
Akiko Matsushita ◽  
Nobuhito Shibata ◽  
...  

1978 ◽  
Vol 45 (3) ◽  
pp. 355-362 ◽  
Author(s):  
I. Gross ◽  
G. J. Smith ◽  
W. M. Maniscalco ◽  
M. R. Czajka ◽  
C. M. Wilson ◽  
...  

We have developed a short-term organ culture model for the study of the biochemical and morphological development of late gestation fetal rat lung. Explants (1 mm3) of 19-day lung were cultured in an oxygen enriched environment in the presence of synthetic serum-free medium for 3 days. Morphological maturation continued in culture. The rate of incorporation of choline into disaturated phosphatidylcholine and the content of this phospholipid in the explants increased in vitro in a pattern very similar to that which occurs in vivo. The activities of choline kinase and cholinephosphotransferase were also similar in cultured lung and in vivo. Studies of glucose oxidation to CO2 provided additional evidence that the explants remained viable in culture. The explants retained the sensitivity of fetal lung to hormonal action. This was demonstrated by the stimulation of choline incorporation into phospholipid by cyclic AMP and an increase in the glycogen content after exposure to insulin.


2011 ◽  
Vol 2 (1) ◽  
pp. 36-48 ◽  
Author(s):  
R. L. Ruhlen ◽  
J. A. Taylor ◽  
J. Mao ◽  
J. Kirkpatrick ◽  
W. V. Welshons ◽  
...  

Exposure of fetuses to endocrine disrupting chemicals (EDCs), such as the estrogenic drug diethylstilbestrol (DES), disrupts development of the reproductive system and affects other aspects of adult phenotype including diseases, consistent with the developmental origins of health and disease hypothesis. To determine whether diet could influence the effects of DES, we compared mice fed a commonly used combination of soy-based Purina 5008 (breeding and lactation) and 5001 (post-weaning) with mice fed soy-based Purina 5002 throughout life. We exposed fetal CD-1 mice (F1) in utero on different feeds to a 0 (controls), low (0.1 μg/kg/day) or high (50 μg/kg/day) dose of DES via feeding the dam (F0) on gestation days 11–17. Compared to 5008, 5002 feed significantly increased serum estradiol in control fetuses. On 5008 (but not 5002) feed, DES significantly increased fetal serum estradiol at a low dose and reduced it at a high dose. Diet influenced the effects of in utero DES on F1 female onset of puberty and the uterine response to estradiol (an inverted-U dose–response relationship seen for DES on uterine weight with 5008/5001 feed was not observed with 5002). Both low- and high-dose DES reduced daily sperm production (DSP) in adult F1 males on 5008/5001 feed, whereas males fed 5002 showed no DES-induced reduction in DSP. Thus, we observed a number of low-dose effects of in utero DES exposure on Purina 5008/5001 feed that were not observed using Purina 5002, a feed commonly used in industry-funded toxicological studies conducted for regulatory purposes.


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