Home About us Contact
|
Home About us Contact | ||
|
|
||
Critical Window (critical + window)
Selected AbstractsDevelopmental toxicity of estrogenic chemicals on rodents and other speciesCONGENITAL ANOMALIES, Issue 2 2002Taisen Iguchi ABSTRACT, Antenatal sex-hormone exposure induces lesions in mouse reproductive organs, which are similar to those in humans exposed in utero to a synthetic estrogen, diethylstilbestrol. The developing organisms including rodents, fish and amphibians are particularly sensitive to exposure to estrogenic chemicals during a critical window. Exposure to estrogens during the critical period induces long-term changes in reproductive as well as non-reproductive organs, including persistent molecular alterations. The antenatal mouse model can be utilized as an indicator of possible long-term consequences of exposure to exogenous estrogenic compounds including possible environmental endocrine disrupters. Many chemicals released into the environment potentially disrupt the endocrine system in wildlife and humans, some of which exhibit estrogenic activity by binding to the estrogen receptors. Estrogen responsive genes, therefore, need to be identified to understand the molecular basis of estrogenic actions. In order to understand molecular mechanisms of estrogenic chemicals on developing organisms, we are identifying estrogen responsive genes using cDNA microarray, quantitative RT-PCR, and differential display methods, and genes related to the estrogen-independent vaginal changes in mice induced by estrogens during the critical window. In this review, discussion of our own findings related to endocrine distuptor issue will be provided. [source] Endocrine disrupters and human pubertyINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 1 2006E. DEN HOND Summary In this overview of the literature, epidemiological research studying the effect of endocrine disrupters on the onset of puberty is summarized. In girls, earlier age at menarche was reported after exposure to polychlorinated biphenyls (PCBs), polybrominated biphenyls (PBBs), persistent pesticides [dichlorodiphenyltrichloroethane (DDT)] and phthalate esters. However, several other studies found no effect of these compounds on age at menarche or pubertal Tanner stages. One study reported a delaying effect of dioxin-like compounds on breast development. In boys, exposure to PCBs, PCDFs or the pesticide endosulfan was associated with delayed puberty or decreased penile length. Much of the results found in population studies are in accordance with experimental studies in animals. However, the mixture of different components with antagonistic effects (oestrogenic, anti-oestrogenic, anti-androgenic) and the limited knowledge about the most critical window for exposure (prenatal, peri-natal and pubertal) may hamper the interpretation of results. [source] Neonatal Lipopolysaccharide Exposure Delays Puberty and Alters Hypothalamic Kiss1 and Kiss1r mRNA Expression in the Female RatJOURNAL OF NEUROENDOCRINOLOGY, Issue 8 2009A. M. I. Knox Immunological challenge experienced in early life can have long-term programming effects on the hypothalamic-pituitary-adrenal axis that permanently influence the stress response. Similarly, neonatal exposure to immunological stress enhances stress-induced suppression of the hypothalamic-pituitary gonadal (HPG) axis in adulthood, but may also affect earlier development, including the timing of puberty. To investigate the timing of the critical window for this programming of the HPG axis, neonatal female rats were injected with lipopolysaccharide (LPS; 50 ,g/kg i.p.) or saline on postnatal days 3 + 5, 7 + 9, or 14 + 16 and monitored for vaginal opening and first vaginal oestrus as markers of puberty. We also investigated the effects of neonatal programming on the development of the expression patterns of kisspeptin (Kiss1) and its receptor (Kiss1r) in hypothalamic sites known to contain kisspeptin-expressing neuronal populations critical to reproductive function: the medial preoptic area (mPOA) and the arcuate nucleus in neonatally-stressed animals. We determined that the critical period for a significant delay in puberty as a result of neonatal LPS exposure is before 7 days of age in the female rat, and demonstrated that Kiss1, but not Kiss1r mRNA, expression in the mPOA is down-regulated in pre-pubertal females. These data suggest that the mPOA population of kisspeptin neurones play a pivotal role in controlling the onset of puberty, and that their function can be affected by neonatal stress. [source] Temporal Vulnerability of Fetal Cerebellar Purkinje Cells to Chronic Binge Alcohol Exposure: Ovine ModelALCOHOLISM, Issue 10 2007Jayanth Ramadoss Background: Human magnetic resonance imaging (MRI) and autopsy studies reveal abnormal cerebellar development in children who had been exposed to alcohol prenatally, independent of the exposure period. Animal studies conducted utilizing the rat model similarly demonstrate a broad period of vulnerability, albeit the third trimester-equivalent of human brain development is reported to be the most vulnerable period, and the first trimester-equivalent exposure produces cerebellar Purkinje cell loss only at high doses of alcohol. However, in the rat model, all 3 trimester-equivalents do not occur prenatally, requiring the assumption that intrauterine environment, placenta, maternal interactions, and parturition do not play an important role in mediating the damage. In this study, we utilized the ovine model, where all 3 trimester-equivalents occur in utero, to determine the critical window of vulnerability of fetal cerebellar Purkinje cells. Methods: Four groups of pregnant sheep were used: first trimester-equivalent pair-fed saline control group, first trimester-equivalent alcohol group (1.75 g/kg), third trimester-equivalent pair-fed saline control group, and third trimester-equivalent alcohol group (1.75 g/kg). The alcohol exposure regimen was designed to mimic a human binge pattern. Alcohol was administered intravenously on 3 consecutive days beginning on day 4 and day 109 of gestation in the first and third trimester-equivalent groups, respectively, and the alcohol treatment was followed by a 4-day inter-treatment interval when the animals were not exposed to alcohol. Such treatment episodes were replicated until gestational day 41 and 132 in the first and third trimester-equivalent groups, respectively. All fetal brains were harvested on day 133 and processed for stereological cerebellar Purkinje cell counting. Results: Significant deficits were found in the fetal cerebellar Purkinje cell number and density in the first and third trimester-equivalent alcohol exposed fetuses compared with those in the saline controls. However, there was no difference between the first and third trimester-equivalent alcohol administered groups. When comparing the present findings to those from a previous study where the duration of alcohol exposure was all 3 trimester-equivalents of gestation, we did not detect a difference in fetal cerebellar Purkinje cell number. Conclusions: We conclude that the fetal cerebellar Purkinje cells are sensitive to alcohol exposure at any time during gestation and that women who engage in binge drinking during the first trimester are at a high risk of giving birth to children with cerebellar damage even if drinking ceases after the first trimester. Our findings also support the hypothesis that only a certain population of Purkinje cells are vulnerable to alcohol-induced depletion irrespective of the timing or duration of alcohol exposure. [source] Microbial exposure, interferon gamma gene demethylation in naïve T-cells, and the risk of allergic diseaseALLERGY, Issue 3 2009P. J. Vuillermin The period of immune programming during early life presents a critical window of opportunity for the prevention of allergic diseases. There is mounting evidence that inappropriate immune programming may involve disruption of specific epigenetic modifications (switches) at immune-related genes. This novel area of research has great potential, as epigenetic changes are known to be sensitive to environmental factors and may therefore provide a mechanistic link for the observed association between specific environmental cues, faulty immune development, and the risk of allergic disease. In addition, the dynamic and potentially reversible nature of epigenetic modifications offers potentially novel targets for therapeutic and/or preventative interventions. We review the evidence that (1) failure to up-regulate the interferon gamma (IFN,) response during infancy is an important determinant of the risk of allergic disease, (2) expression of the IFN, gene in naïve T-cells is regulated by epigenetic mechanisms, and (3) failure to up-regulate IFN, gene expression of naïve T-cells associated with low early life microbial exposure. Taken together, these lines of evidence suggest that low microbial exposure during early life increases the risk of allergic disease by reducing demethylation (activation) of the IFN, gene of naive T-cells. [source] Presumptive pre-sertoli cells express genes involved in cell proliferation and cell signalling during a critical window in early testis differentiationMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 12 2007Aron T. Cory In mammals, the pre-Sertoli cell of the male genital ridge is the first cell type to display sex specific differentiation and differential gene expression. The genetic cascade driving the differentiationof pre-Sertoli cells and ultimately testis formationis beginning to be unravelled, but many questions remain. A better understanding of the transcriptome of pre-Sertoli cells immediately after sex determination is essential in order to further understand this differentiationprocess. A mouse model expressing Red Fluorescent Protein (RFP) under the control of a hybrid mouse/pig SRY promoter (HybSRYp-RFP) was used to purify cells from embryonic day 12.0 (e12.0) male genital ridges. To compare the transcriptomes of HybSRYp-RFP cell populations versus age matched whole female genital ridges, RNA was extracted and used to generate molecular probes that were hybridized onto Affymetrix Mouse Genome 430 2.0 micro-arrays. The expression of genes considered markers for pre-Sertoli cells, including Sox9, Mis, Dhh and Fgf9 were identified within the HybSRYp-RFP expressing cell population, while markers for germ cells (Oct4, SSEA-1) and endothelial cells (Ntrk3) were not identified. In contrast, markers for ovarian somatic cell expression, including Fst and Bmp2, were identified as overexpressed within the ovarian cell population. In a general fashion, genes identified as 2.5-fold over expressed in HybSRYp-RFP expressing cells coded notably for cell signalling and extra cellular proteins. The expression of Sox10, Stc2, Fgf18, Fgf13 and Wnt6 were further characterized via whole mount in situ hybridization (WISH) on male and female genital ridges between e11.5 and e14.5. Sox10, Fgf18, Fgf13 and Stc2 gene expression was detected within the male genital ridges while Wnt6 was found diffusely within both the male and female genital ridges. These data represent the earliest comprehensive microarray expression analysis of purified presumptive pre-Sertoli cells available to date. Mol. Reprod. Dev. 74: 1491,1504, 2007. © 2007 Wiley-Liss, Inc. [source] Genesis of teratogen-induced holoprosencephaly in mice,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 1 2010Robert J. Lipinski Abstract Evidence from mechanical, teratological, and genetic experimentation demonstrates that holoprosencephaly (HPE) typically results from insult prior to the time that neural tube closure is completed and occurs as a consequence of direct or indirect insult to the rostral prechordal cells that induce the forebrain or insult to the median forebrain tissue, itself. Here, we provide an overview of normal embryonic morphogenesis during the critical window for HPE induction, focusing on the morphology and positional relationship of the developing brain and subjacent prechordal plate and prechordal mesoderm cell populations. Subsequent morphogenesis of the HPE spectrum is then examined in selected teratogenesis mouse models. The temporal profile of Sonic Hedgehog expression in rostral embryonic cell populations and evidence for direct or indirect perturbation of the Hedgehog pathway by teratogenic agents in the genesis of HPE is highlighted. Emerging opportunities based on recent insights and new techniques to further characterize the mechanisms and pathogenesis of HPE are discussed. © 2010 Wiley-Liss, Inc. [source] Witnessing Community Violence and Health-Risk Behaviors Among Detained AdolescentsAMERICAN JOURNAL OF ORTHOPSYCHIATRY, Issue 4 2007Dexter R. Voisin PhD This study examines whether witnessing community violence, in the 12 months prior to juvenile detention, is related and health-related outcomes in the 2 months prior to being detained among 550 youth. Participants answered survey questions using audio-computer assisted self-interviewing procedures, which assessed demographic, problem, and drug and sexual risk behaviors. Multiple logistic regression analyses, controlling for significant covariates, indicated that adolescents, in the last 12 months, who reported witnessing community violence, relative to their peer witnessing no violence, were in the last 2 months prior to being detained, twice more likely to have suicidal threats, 2 times more likely to use marijuana and alcohol, 2 times more likely to get high on alcohol or other drugs during sexual intercourse, and 2 times more likely to have sex with a partner who was high on alcohol or other drugs. Finding suggest that detained youth, many of whom may not access traditional helath care, should be offered prevention and intervention services dring detention, which provides a critical window of opportunity for needed services. [source] Short periods of prenatal stress affect growth, behaviour and hypothalamo,pituitary,adrenal axis activity in male guinea pig offspringTHE JOURNAL OF PHYSIOLOGY, Issue 3 2005Amita Kapoor Prenatal stress can have profound long-term influences on physiological function throughout the course of life. We hypothesized that focused periods of moderate prenatal stress at discrete time points in late gestation have differential effects on hypothalamo,pituitary,adrenal (HPA) axis function in adult guinea pig offspring, and that changes in HPA axis function will be associated with modification of anxiety-related behaviour. Pregnant guinea pigs were exposed to a strobe light for 2 h on gestational days (GD) 50, 51, 52 (PS50) or 60, 61, 62 (PS60) (gestation length ,70 days). A control group was left undisturbed throughout pregnancy. Behaviour was assessed in male offspring on postnatal day (PND)25 and PND70 by measurement of ambulatory activity and thigmotaxis (wall-seeking behaviour) in a novel open field environment. Subsequent to behavioural testing, male offspring were cannulated (PND75) to evaluate basal and activated HPA axis function. Body weight was significantly decreased in adult PS50 and PS60 offspring and this effect was apparent soon after weaning. The brain-to-body-weight ratio was significantly increased in adult PS50 males. Basal plasma cortisol levels were elevated in PS50 male offspring throughout the 24 h sampling period compared with controls. In response to an ACTH challenge and to exposure to an acute stressor, PS60 male offspring exhibited elevated plasma cortisol responses. Plasma testosterone concentrations were strikingly decreased in PS50 offspring. Thigmotaxis in the novel environment was increased in PS50 male offspring at PND25 and PND70, suggesting increased anxiety in these animals. In conclusion, prenatal stress during critical windows of neuroendocrine development programs growth, HPA axis function, and stress-related behaviour in adult male guinea pig offspring. Further, the nature of the effect is dependant on the timing of the maternal stress during pregnancy. [source] | |||||||||||||