scholarly journals In Utero Exposure to the Endocrine Disruptor Di-(2-Ethylhexyl) Phthalate Induces Long-Term Changes in Gene Expression in the Adult Male Adrenal Gland

Endocrinology ◽  
2014 ◽  
Vol 155 (5) ◽  
pp. 1667-1678 ◽  
Author(s):  
D.B. Martinez-Arguelles ◽  
E. Campioli ◽  
C. Lienhart ◽  
J. Fan ◽  
M. Culty ◽  
...  

The plasticizer di-(2-ethylhexyl) phthalate (DEHP) is used to add flexibility to polyvinylchloride polymers and as a component of numerous consumer and medical products. DEHP and its metabolites have been detected in amniotic fluid and umbilical cord blood, suggesting fetal exposure. In the present study, we used an in utero exposure model in which pregnant rat dams were exposed to 1- to 300-mg DEHP/kg·d from gestational day 14 until birth. We previously reported that this window of exposure to environmentally relevant doses of DEHP resulted in reduced levels of serum testosterone and aldosterone in adult male offspring and that the effects on aldosterone were sustained in elderly rats and resulted in decreased blood pressure. Here, we characterized the long-term effects of in utero DEHP exposure by performing global gene expression analysis of prepubertal (postnatal d 21) and adult (postnatal d 60) adrenal glands. We found that the peroxisome proliferator-activated receptor and lipid metabolism pathways were affected by DEHP exposure. Expression of 2 other DEHP targets, hormone-sensitive lipase and phosphoenolpyruvate carboxykinase 1 (Pck1), correlated with reduced aldosterone levels and may account for the inhibitory effect of DEHP on adrenal steroid formation. The angiotensin II and potassium pathways were up-regulated in response to DEHP. In addition, the potassium intermediate/small conductance calcium-activated channel Kcnn2 and 2-pore-domain potassium channel Knck5 were identified as DEHP targets. Based on this gene expression analysis, we measured fatty acid-binding protein 4 and phosphoenolpyruvate carboxykinase 1 in sera from control and DEHP-exposed rats and identified both proteins as putative serum biomarkers of in utero DEHP exposure. These results shed light on molecular targets that mediate DEHP long-term effects and, in doing so, provide means by which to assess past DEHP exposure.

2018 ◽  
Vol 32 (10) ◽  
pp. e13373
Author(s):  
Hui Tzu Lin-Wang ◽  
Reginaldo Cipullo ◽  
João Italo Dias França ◽  
Marco Aurelio Finger ◽  
Joao Manoel Rossi Neto ◽  
...  

2011 ◽  
Vol 2011 (1) ◽  
Author(s):  
Susanne Lund Kristensen ◽  
Cecilia Høst Ramlau-Hansen ◽  
Erik Ernst ◽  
Sjurdur Frodi Olsen ◽  
Jens Peter Bonde ◽  
...  

2017 ◽  
Vol 6 (1) ◽  
pp. 15 ◽  
Author(s):  
Yousof Gheisari ◽  
Shiva Moein ◽  
ShaghayeghHaghjooy Javanmard ◽  
Maryam Abedi ◽  
MohammadHosein Izadpanahi

2021 ◽  
Vol 23 (3) ◽  
Author(s):  
Hamid Noghanibehambari ◽  
Farzaneh Noghani ◽  
Nahid Tavassoli ◽  
Mostafa Toranji

Endocrinology ◽  
2020 ◽  
Vol 161 (12) ◽  
Author(s):  
Zhihao Wang ◽  
Myles H Alderman ◽  
Cyrus Asgari ◽  
Hugh S Taylor

Abstract In utero Bisphenol A (BPA) exposure has been linked to many deficits during brain development, including sexual differentiation, behavior, and motor coordination. Yet, how BPA induces these disorders and whether its effects are long lasting are largely unknown. In this study, using a mouse model, we demonstrated that in utero exposure to an environmentally relevant dose of BPA induced locomotor deficits, anxiety-like behavior, and declarative memory impairments that persisted into old age (18 months). Compared to the control animals, the BPA-exposed mice had a significant decrease in locomotor activity, exploratory tendencies, and long-term memory, and an increase in anxiety. The global brain gene expression profile was altered permanently by BPA treatment and showed regional and sexual differences. The BPA-treated male mice had more changes in the hippocampus, while female mice experienced more changes in the cortex. Overall, we demonstrate that in utero exposure to BPA induces permanent changes in brain gene expression in a region-specific and sex-specific manner, including a significant decrease in locomotor activity, learning ability, long-term memory, and an increase in anxiety. Fetal/early life exposures permanently affect neurobehavioral functions that deteriorate with age; BPA exposure may compound the effects of aging.


2002 ◽  
Vol 8 (2-3) ◽  
pp. 254-260
Author(s):  
G. Mokhtar ◽  
E. Hossny ◽  
M. El Awady ◽  
M. Zekry

Serum cadmium levels at delivery were measured in a consecutive sample of 100 mother-infant pairs in Egypt using venous blood from mothers and umbilical cord blood from neonates. The serum cadmium levels of mothers ranged from 0.4 to 2.2 microg/L [mean 0.73 microg/L] and of infants from 0.2 to 1.5 microg/L [mean 0.66 microg/L]. Infant cadmium levels were about 70% of maternal levels in most pairs. Serum cadmium was significantly higher in mothers and babies passively exposed to tobacco smoke. Five-minute Apgar scores were negatively correlated with cord blood cadmium levels. The cadmium levels did not differ between subjects from Cairo and Giza or according to urban, suburban or rural areas. Thus, in utero exposure to cadmium was evident and wider-scale studies on its long-term effects are recommended.


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