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Gene expression in teratogenic exposures: a new approach to understanding individual risk.

ABSTRACT: The phenomenon of partial or incomplete penetrance is common to many paradigms of exposure to teratogens, where only some of the exposed individuals exhibit developmental defects. We here argue that the most widely used experimental approaches in reproductive toxicology do not take partial penetrance into account, and are thus likely to miss differences between affected and unaffected individuals that contribute to susceptibility for teratogenesis. We propose that focus on the variation between exposed individuals could help to discover factors that may play a causative role for abnormal developmental processes that occur with incomplete penetrance.

SUBMITTER: Kappen C

PROVIDER: S-EPMC4066898 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Gene expression in teratogenic exposures: a new approach to understanding individual risk.

Kappen Claudia C Salbaum J Michael JM

Reproductive toxicology (Elmsford, N.Y.) 20140131

The phenomenon of partial or incomplete penetrance is common to many paradigms of exposure to teratogens, where only some of the exposed individuals exhibit developmental defects. We here argue that the most widely used experimental approaches in reproductive toxicology do not take partial penetrance into account, and are thus likely to miss differences between affected and unaffected individuals that contribute to susceptibility for teratogenesis. We propose that focus on the variation between ...[more]

PMID: 24491834

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Gene expression in teratogenic exposures: a new approach to understanding individual risk

2013-12-31 | GSE50600 | GEO

Gene expression in teratogenic exposures: a new approach to understanding individual risk

Project description:The phenomenon of partial or incomplete penetrance is common to many paradigms of exposure to teratogens, where only some of the exposed individuals exhibit developmental defects. We here argue that the most widely used experimental approaches in reproductive toxicology do not take partial penetrance into account, and are thus likely to miss differences between affected and unaffected individuals that contribute to susceptibility for teratogenesis. We propose that focus on the variation between exposed individuals could help to discover factors that may play a causative role for abnormal developmental processes that occur with incomplete penetrance. Total RNA was extracted from individual embryos E10.5 derived from normal and diabetic pregnancies. A total of 8 sample pools were created, 4 resultiing from normal (C1-C4) and 4 from diabetic (E1-E4) pregnancies. Each pool consisted of RNA from 4 embryos obtained from 4 different pregnancies. Samples E5-E8 consisted of individual embryos with NT defects obtained from diabetic pregnancies.

2013-12-31 | E-GEOD-50600 | biostudies-arrayexpress

Global gene expression analysis reveals pathway differences between teratogenic and non-teratogenic exposure concentrations of bisphenol A and 17?-estradiol in embryonic zebrafish.

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| S-EPMC3690774 | biostudies-literature

microRNAs and the mammary gland: A new understanding of gene expression.

Project description:MicroRNAs (miRNAs) have been identified in cells as well as in exosomes in biological fluids such as milk. In mammary gland, most of the miRNAs studied have functions related to immunity and show alterations in their pattern of expression during lactation. In mastitis, the inflammatory response caused by Streptococcus uberis alters the expression of miRNAs that may regulate the innate immune system. These small RNAs are stable at room temperature and are resistant to repeated freeze/thaw cycles, acidic conditions and degradation by RNAse, making them resistant to industrial procedures. These properties mean that miRNAs could have multiple applications in veterinary medicine and biotechnology. Indeed, lactoglobulin-free milk has been produced in transgenic cows expressing specific miRNAs. Although plant and animal miRNAs have undergone independent evolutionary adaptation recent studies have demonstrated a cross-kingdom passage in which rice miRNA was isolated from human serum. This finding raises questions about the possible effect that miRNAs present in foods consumed by humans could have on human gene regulation. Further studies are needed before applying miRNA biotechnology to the milk industry. New discoveries and a greater knowledge of gene expression will lead to a better understanding of the role of miRNAs in physiology, nutrition and evolution.

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Clustering gene expression regulators: new approach to disease subtyping.

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Low rates of pregnancy screening in adolescents before teratogenic exposures in a national sample of children's hospitals.

Project description:Adolescents with cancer engage in sexual behaviors and are exposed to teratogenic chemotherapy. There are no data regarding pregnancy screening patterns for adolescents before chemotherapy exposure.A cross-sectional study of leukemia and emergency room (ER) admissions in the Pediatric Health Information System from 1999 to 2011 was conducted. Females who were 10 to 18 years old and 1) had newly diagnosed acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) or 2) had ER visits with computed tomography (CT) of the abdomen/pelvis were included. The exposure was a hospital visit with either chemotherapy or an abdominal/pelvic CT scan. The main outcome was a pregnancy test billed on the same day or before the teratogenic exposure within the same index admission. Log-binomial regressions were used to compute prevalence ratios and 95% confidence intervals comparing pregnancy screening in the leukemia and ER cohorts.A total of 35,650 admissions were identified. The proportion of visits with an appropriately timed pregnancy test was 35%, 64%, and 58% in the ALL (n?=?889), AML (n?=?127), and ER cohorts (n?=?34,634), respectively. Patients with ALL were significantly less likely to have a pregnancy test than the ER cohort (adjusted prevalence ratio, 0.71; 95% confidence interval, 0.65-0.78), but there was no significant difference between the AML and ER cohorts (adjusted prevalence ratio, 1.12; 95% confidence interval, 0.99-1.27). There was substantial hospital-level variation in pregnancy screening patterns.Adolescents with acute leukemia and ER visits have low rates of pregnancy screening before teratogenic exposures. Standardized practice guidelines for pregnancy screening among adolescents may improve screening rates. Cancer 2016;122:3394-3400. © 2016 American Cancer Society.

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| S-EPMC7791999 | biostudies-literature

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