Prenatal Octamethylcyclotetrasiloxane Exposure Impaired Proliferation of Neuronal Progenitor, Leading to Motor, Cognition, Social and Behavioral Functions.

Cyclic siloxane octamethylcyclotetrasiloxane (D4) has raised concerns as an endocrine-disrupting chemical (EDC). D4 is widely used in detergent products, cosmetics, and personal care products. Recently, robust toxicological data for D4 has been reported, but the adverse effects of D4 on brain development are unknown. Here, pregnant mice on gestational day 9.5 were treated daily with D4 to postnatal day 28, and the offspring mice were studied. The prenatal D4-treated mice exhibited cognitive dysfunction, limited memory, and motor learning defect. Moreover, prenatal D4 exposure reduced the proliferation of neuronal progenitors in the offspring mouse brain. Next, the mechanisms through which D4 regulated the cell cycle were investigated. Aberrant gene expression, such as cyclin-dependent kinases CDK6 and cyclin-dependent kinase inhibitor p27, were found in the prenatal D4-treated mice. Furthermore, the estrogen receptors ERa and ERb were increased in the brain of prenatal D4-treated mice. Overall, these findings suggest that D4 exerts estrogen activity that affects the cell cycle progression of neuronal progenitor cells during neurodevelopment, which may be associated with cognitive deficits in offspring.

Induction of the Estrogenic Marker Calbindn-D9k by Octamethylcyclotetrasiloxane.

Interrupting the hormonal balance of an organism by interfering with hormones and their target receptors gives rise to various problems such as developmental disorders. Collectively, these reagents are known as endocrine disruptors (EDs). Cyclic volatile methyl siloxanes (cVMSs) are a group of silicone polymers that including octamethylcyclotetrasiloxane (D4). In the present study, we examined the estrogenicity of D4 through in vitro and in vivo assays that employed calcium-binding protein 9K (calbindin-D9k; CaBP-9K) as a biomarker. For in vitro investigation, GH3 rat pituitary cells were exposed to vehicle, 17ß-estradiol (E2), or D4 with/without ICI 182 780 (ICI). CaBP-9K and progesterone receptor (PR) both were up-regulated by E2 and D4 which were completely blocked by ICI. Transcription of estrogen receptor α (ER α) was decreased by E2 and D4 but increased by ICI. D4 was also administered to immature female rats for an uterotrophic (UT) assay and detection of CaBP-9K. Ethinyl estradiol (EE) or D4 was administered subcutaneously with or without ICI. Although uterine weight was not significant altered by D4, an effect thought to be due to cytochrome P450 (CYP), it induced CaBP-9K and PR gene expression. Based on these results we reveal that D4 has estrogenic potential proven under in vitro and in vivo experimental conditions.

Anti-inflammatory effects of essential oils from Chamaecyparis obtusa via the cyclooxygenase-2 pathway in rats.

Essential oils are concentrated hydrophobic liquids containing volatile aromatic compounds from plants. In the present study, the essential oil of Chamaecyparis obtusa (C. obtusa), which is commercially used in soap, toothpaste and cosmetics, was extracted. Essential oil extracted from C. obtusa contains several types of terpenes, which have been shown to have anti-oxidative and anti-inflammatory effects. In the present study, we examined the anti-inflammatory effects of C. obtusa essential oil in vivo and in vitro following the induction of inflammation by lipopolysaccharides (LPS) in rats. While LPS induced an inflammatory response through the production of prostaglandin E2 (PGE2) in the blood and peripheral blood mononuclear cells (PMNCs), these levels were reduced when essential oil was pre-administered. Additionally, the mechanism of action underlying the anti-inflammatory effects of C. obtusa essential oil was investigated by measuring the mRNA expression of inflammation­associated genes. LPS treatment significantly induced the expression of transforming growth factor α (TNFα) and cyclooxygenase-2 (COX-2) in rats, while C. obtusa essential oil inhibited this effect. Taken together, our results demonstrate that C. obtusa essential oil exerts anti­inflammatory effects by regulating the production of PGE2 and TNFα gene expression through the COX-2 pathway. These findings suggest that C. obtusa essential oil may constitute a novel source of anti-inflammatory drugs.