PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-4 (4)
 

Clipboard (0)
None

Select a Filter Below

Journals
Year of Publication
Document Types
1.  Evaluation of the Association between Maternal Smoking, Childhood Obesity, and Metabolic Disorders: A National Toxicology Program Workshop Review 
Environmental Health Perspectives  2012;121(2):170-180.
Background: An emerging literature suggests that environmental chemicals may play a role in the development of childhood obesity and metabolic disorders, especially when exposure occurs early in life.
Objective: Here we assess the association between these health outcomes and exposure to maternal smoking during pregnancy as part of a broader effort to develop a research agenda to better understand the role of environmental chemicals as potential risk factors for obesity and metabolic disorders.
Methods: PubMed was searched up to 8 March 2012 for epidemiological and experimental animal studies related to maternal smoking or nicotine exposure during pregnancy and childhood obesity or metabolic disorders at any age. A total of 101 studies—83 in humans and 18 in animals—were identified as the primary literature.
Discussion: Current epidemiological data support a positive association between maternal smoking and increased risk of obesity or overweight in offspring. The data strongly suggest a causal relation, although the possibility that the association is attributable to unmeasured residual confounding cannot be completely ruled out. This conclusion is supported by findings from laboratory animals exposed to nicotine during development. The existing literature on human exposures does not support an association between maternal smoking during pregnancy and type 1 diabetes in offspring. Too few human studies have assessed outcomes related to type 2 diabetes or metabolic syndrome to reach conclusions based on patterns of findings. There may be a number of mechanistic pathways important for the development of aberrant metabolic outcomes following perinatal exposure to cigarette smoke, which remain largely unexplored.
Conclusions: From a toxicological perspective, the linkages between maternal smoking during pregnancy and childhood overweight/obesity provide proof-of-concept of how early-life exposure to an environmental toxicant can be a risk factor for childhood obesity.
doi:10.1289/ehp.1205404
PMCID: PMC3569686  PMID: 23232494
animal; chemically induced/epidemiology; diabetes; environmental epidemiology; glucose; insulin; maternal smoking toxicity; metabolism; nicotine toxicity; obesity
2.  Estrogen Receptor-α Mediates Diethylstilbestrol-Induced Feminization of the Seminal Vesicle in Male Mice 
Environmental Health Perspectives  2012;120(4):560-565.
Background: Studies have shown that perinatal exposure to the synthetic estrogen diethylstilbestrol (DES) leads to feminization of the seminal vesicle (SV) in male mice, as illustrated by tissue hyperplasia, ectopic expression of the major estrogen-inducible uterine secretory protein lactoferrin (LF), and reduced expression of SV secretory protein IV (SVS IV).
Objectives: The present study was designed to evaluate the role of the estrogen receptor (ER) in this action by using ER-knockout (ERKO) mice.
Methods: Wild-type (WT), ERα-null (αERKO), and ERβ-null (βERKO) male mice were treated with either vehicle or DES (2 μg/day) on neonatal days 1–5. These mice were divided into two groups: In the first group, intact mice were sacrificed at 10 weeks of age; in the second group, mice were castrated at 10 weeks of age, allowed to recover for 10 days, treated with dihydrotestosterone (DHT) or placebo, and sacrificed 2 weeks later. Body weights and SV weights were recorded, and mRNA expression levels of Ltf (lactoferrin), Svs4, and androgen receptor (Ar) were assessed.
Results: In DES-treated intact mice, SV weights were reduced in WT and βERKO mice but not in αERKO mice. DES-treated WT and βERKO males, but not αERKO males, exhibited ectopic expression of LF in the SV. DES treatment resulted in decreased SVS IV protein and mRNA expression in WT males, but no effect was seen in αERKO mice. In addition, DES-treated βERKO mice exhibited reduced Svs4 mRNA expression but maintained control levels of SVS IV protein. In DES-treated castrated mice, DHT implants restored SV weights to normal levels in αERKO mice but not in WT mice, suggesting full androgen responsiveness in αERKO mice.
Conclusions: These data suggest that DES-induced SV toxicity and feminization are primarily mediated by ERα; however, some aspects of androgen response may require the action of ERβ.
doi:10.1289/ehp.1103678
PMCID: PMC3339448  PMID: 22275727
development; endocrine disruptor; reproductive tract
3.  Spontaneous Airway Hyperresponsiveness in Estrogen Receptor-α–deficient Mice 
Rationale: Airway hyperresponsiveness is a critical feature of asthma. Substantial epidemiologic evidence supports a role for female sex hormones in modulating lung function and airway hyperresponsiveness in humans.
Objectives: To examine the role of estrogen receptors in modulating lung function and airway responsiveness using estrogen receptor–deficient mice.
Methods: Lung function was assessed by a combination of whole-body barometric plethysmography, invasive measurement of airway resistance, and isometric force measurements in isolated bronchial rings. M2 muscarinic receptor expression was assessed by Western blotting, and function was assessed by electrical field stimulation of tracheas in the presence/absence of gallamine. Allergic airway disease was examined after ovalbumin sensitization and exposure.
Measurements and Main Results: Estrogen receptor-α knockout mice exhibit a variety of lung function abnormalities and have enhanced airway responsiveness to inhaled methacholine and serotonin under basal conditions. This is associated with reduced M2 muscarinic receptor expression and function in the lungs. Absence of estrogen receptor-α also leads to increased airway responsiveness without increased inflammation after allergen sensitization and challenge.
Conclusions: These data suggest that estrogen receptor-α is a critical regulator of airway hyperresponsiveness in mice.
doi:10.1164/rccm.200509-1493OC
PMCID: PMC1899278  PMID: 17095746
lung function; asthma; hyperreactivity; M2 muscarinic receptor; estrogen receptor
4.  Spontaneous Airway Hyperresponsiveness in Estrogen Receptor-α–deficient Mice 
Rationale
Airway hyperresponsiveness is a critical feature of asthma. Substantial epidemiologic evidence supports a role for female sex hormones in modulating lung function and airway hyperresponsiveness in humans.
Objectives
To examine the role of estrogen receptors in modulating lung function and airway responsiveness using estrogen receptor–deficient mice.
Methods
Lung function was assessed by a combination of whole-body barometric plethysmography, invasive measurement of airway resistance, and isometric force measurements in isolated bronchial rings. M2 muscarinic receptor expression was assessed by Western blotting, and function was assessed by electrical field stimulation of tracheas in the presence/absence of gallamine. Allergic airway disease was examined after ovalbumin sensitization and exposure.
Measurements and Main Results
Estrogen receptor-α knockout mice exhibit a variety of lung function abnormalities and have enhanced airway responsiveness to inhaled methacholine and serotonin under basal conditions. This is associated with reduced M2 muscarinic receptor expression and function in the lungs. Absence of estrogen receptor-α also leads to increased airway responsiveness without increased inflammation after allergen sensitization and challenge.
Conclusions
These data suggest that estrogen receptor-α is a critical regulator of airway hyperresponsiveness in mice.
doi:10.1164/rccm.200509-1493OC
PMCID: PMC1899278  PMID: 17095746
lung function; asthma; hyperreactivity; M2 muscarinic receptor; estrogen receptor

Results 1-4 (4)