A human-relevant mixture of endocrine disrupting chemicals induces changes in hippocampal DNA methylation correlating with hyperactive behavior in male mice.

Humans are ubiquitously exposed to endocrine disrupting chemicals (EDCs), substances that interfere with endogenous hormonal signaling. Exposure during early development is of particular concern due to the programming role of hormones during this period. A previous epidemiological study has shown association between prenatal co-exposure to 8 EDCs (Mixture N1) and language delay in children, suggesting an effect of this mixture on neurodevelopment.

In utero exposure to phthalates and reproductive toxicity in rodents.

Phthalates, widely used as plasticizers, are contained in many everyday products. Human biomonitoring studies detect their presence in biological fluids of a large part of the population worldwide. Maternal exposure during pregnancy has been related with aberrations in the reproductive growth of male infants.

Long term transcriptional and behavioral effects in mice developmentally exposed to a mixture of endocrine disruptors associated with delayed human neurodevelopment.

Accumulating evidence suggests that gestational exposure to endocrine disrupting chemicals (EDCs) may interfere with normal brain development and predispose for later dysfunctions. The current study focuses on the exposure impact of mixtures of EDCs that better mimics the real-life situation. We herein describe a mixture of phthalates, pesticides and bisphenol A (mixture N1) detected in pregnant women of the SELMA cohort and associated with language delay in their children.

Synergistic effects of early life mild adversity and chronic social defeat on rat brain microglia and cytokines.

Exposure to early life stress affects the development and function of the brain and when followed by adversities in adulthood, the negative effects of stress are enhanced. Microglia has been proposed as a potential mediator of this phenomenon. In the present study, we investigated the long-term effects of mild early life stress, the consequences of a stressor in adulthood as well as their interaction on microglial and cytokine (PPARγ, IL-1β and TNFα) levels in the brain of adult male rats.

Gestational exposure to an epidemiologically defined mixture of phthalates leads to gonadal dysfunction in mouse offspring of both sexes.

The increasing concern for the reproductive toxicity of abundantly used phthalates requires reliable tools for exposure risk assessment to mixtures of chemicals, based on real life human exposure and disorder-associated epidemiological evidence. We herein used a mixture of four phthalate monoesters (33% mono-butyl phthalate, 16% mono-benzyl phthalate, 21% mono-ethyl hexyl phthalate, and 30% mono-isononyl phthalate), detected in 1 trimester urine of 194 pregnant women and identified as bad actors for a shorter anogenital distance (AGD) in their baby boys. Mice were treated with 0, 0.

c-MYC targets the central oscillator gene Per1 and is regulated by the circadian clock at the post-transcriptional level.

Cell proliferation in mammals follows a circadian rhythm while disruption of clock gene expression has been linked to tumorigenesis. Expression of the c-Myc oncogene is frequently deregulated in tumors, facilitating aberrant cell proliferation. c-MYC protein levels display circadian rhythmicity, which is compatible with an in vitro repressive role of the clock-activating complex BMAL1/CLOCK on its promoter.

The circadian expression of c-MYC is modulated by the histone deacetylase inhibitor trichostatin A in synchronized murine neuroblastoma cells.

Circadian clocks govern the mammalian physiology in a day/night-dependent manner. The circadian oscillator of peripheral organs is composed of the same elements as the central pacemaker at the suprachiasmatic nucleus (SCN). The interaction between the circadian clock and several cell cycle components has been established in recent years, since many key regulators of cell cycle and growth control were proved to be rhythmically expressed.