Faculty Opinions recommendation of Acute and long-term effects of in utero exposure of rats to di(n-butyl) phthalate on testicular germ cell development and proliferation.

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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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 ◽

10.1210/en.2013-1921 ◽

2014 ◽

Vol 155 (5) ◽

pp. 1667-1678 ◽

Cited By ~ 23

Author(s):

D.B. Martinez-Arguelles ◽

E. Campioli ◽

C. Lienhart ◽

J. Fan ◽

M. Culty ◽

...

Keyword(s):

Gene Expression ◽

Expression Analysis ◽

Phosphoenolpyruvate Carboxykinase ◽

Gene Expression Analysis ◽

In Utero ◽

In Utero Exposure ◽

Long Term Effects ◽

Ethylhexyl Phthalate ◽

Dehp Exposure

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.

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