Unknown,Transcriptomics,Genomics,Proteomics

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Transcriptomic effects of early life and peripubertal dietary vitamin D deficiency on mouse ovaries

ABSTRACT: Vitamin D2 (VD) and the VD3 receptor (VDR) are proposed to have multiple important physiological roles that include but are not limited to glucose homeostasis, bone health, immune competency and more recently maintenance of normal reproductive physiology. The prevalence of VD deficiency in the US is reported to be as high as 60% in some populations. Several recent studies suggest that reproductive-aged women and their offspring are at the greatest risk for VD deficiency. The objective of our study was to determine the effect of early life (intrauterine through preweaning) and peripubertal VD deficiency on female reproductive physiology. Profile and compare the ovarian transcriptomes of 2-month-old C57BL/6J mice that received a normal (OC samples) or a VD-deficient diet only during the early life (OE samples) or peripubertal (OP samples). Each diet group (OC, OE and OP) was composed of 4 females (biological replicas).

ORGANISM(S): Mus musculus

SUBMITTER: Dumitru Iacobas

PROVIDER: E-GEOD-48167 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Contamination of the environment with endocrine disrupting chemicals (EDCs) has raised concerns about potential health hazards for humans and wildlife. P-tert-octylphenol (OP) is one such ubiquitous chemical reported to bind to the estrogen receptor (ER) and alter expression of estrogen-responsive genes. Human and wildlife exposure to OP are likely, due to its persistence in the environment and its presence in food, water and items of daily use. Detrimental effects of OP exposures on the reproductive system have been observed in some, but not all, in vivo experiments. This study compared estrogenic effects of OP in vitro with those in vivo in adult female rats, attempting to better mimic real-life exposures in adults. In vitro, OP bound to human ER weakly and accelerated proliferation of MCF-7 cells. Adult Sprague-Dawley rats were given OP by gavage either once (125 mg/kg OP) or daily for 35 days (25, 50, 125 mg/kg). Body and organ weights and ovarian follicle populations were unaltered in OP-exposed adult rats after either time point, despite detectable levels of OP in reproductive organs. Toxicity of OP was demonstrated by a slightly reduced growth rate and slightly altered estrous cycle, but there were no significant estrogen-like changes in histomorphology or microarray analyses of gene expression of uterine tissue. Prepubertal rats exposed by gavage to 125 or 250 mg/kg OP for three days failed to show any uterotrophic effects, although E2 caused a 3-fold increase in uterine weight. These results do not support a dose-dependent, estrogenic mode of action for OP. Keywords: treatment vs control Individual uterine RNA samples from 4 female 35-day old rats per treatment (4 OP and 4 vehicle) sacrificed on the second day of diestrus after 35 days of exposure to OP (125 mg/kg/day in propylene glycol) or solvent (propylene glycol, PG) by gavage were compared with liver RNA pooled from all 8 rats (as reference, combined OP and solvent treatment groups). Comparisons were made between treatments. Liver cDNA was always marked with Cy5 and uterine cDNA was always marked with Cy3.

Project description:Contamination of the environment with endocrine disrupting chemicals (EDCs) has raised concerns about potential health hazards for humans and wildlife. P-tert-octylphenol (OP) is one such ubiquitous chemical reported to bind to the estrogen receptor (ER) and alter expression of estrogen-responsive genes. Human and wildlife exposure to OP are likely, due to its persistence in the environment and its presence in food, water and items of daily use. Detrimental effects of OP exposures on the reproductive system have been observed in some, but not all, in vivo experiments. This study compared estrogenic effects of OP in vitro with those in vivo in adult female rats, attempting to better mimic real-life exposures in adults. In vitro, OP bound to human ER weakly and accelerated proliferation of MCF-7 cells. Adult Sprague-Dawley rats were given OP by gavage either once (125 mg/kg OP) or daily for 35 days (25, 50, 125 mg/kg). Body and organ weights and ovarian follicle populations were unaltered in OP-exposed adult rats after either time point, despite detectable levels of OP in reproductive organs. Toxicity of OP was demonstrated by a slightly reduced growth rate and slightly altered estrous cycle, but there were no significant estrogen-like changes in histomorphology or microarray analyses of gene expression of uterine tissue. Prepubertal rats exposed by gavage to 125 or 250 mg/kg OP for three days failed to show any uterotrophic effects, although E2 caused a 3-fold increase in uterine weight. These results do not support a dose-dependent, estrogenic mode of action for OP. Keywords: treatment-control Individual uterine RNA samples from 4 female ~35-day old rats per treatment (4 OP and 4 vehicle) sacrificed on the second day of diestrus after a single dose of OP (125 mg/kg/day in propylene glycol) or solvent (propylene glycol, PG) by gavage on the first day of diestrus were compared with liver RNA pooled from all 8 rats (as reference, combined OP and solvent treatment groups). Comparisons were made between treatments. Liver cDNA was always marked with Cy5 and uterine cDNA was always marked with Cy3.

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Transcriptomic effects of early life and peripubertal dietary vitamin D deficiency on mouse ovaries

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