Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA138871 | ENA |
REPOSITORIES: ENA
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Project description:Akt1 plays a protective role in the postnatal C57BL6 mouse testis following lactational exposure to the neonatal goitrogen, propylthiouracil (PTU). To elucidate the transcriptional profile mediating this phenotypic effect, we monitored changes in testicular gene expression at postnatal days (PNDs) 15 and 25 in Akt1+/+, Akt1+/-, and Akt1-/- testes following exposure to 0.01% PTU allowing us to determine changes in gene expression due to 1.) genotype effects; 2.) exposure effects; and 3.) genotype-by-exposure interactions. Early PTU-dependent gene changes included genes involved in lipid metabolism, spermatid differentiation, meiosis and adhesion. Early Akt1-dependent effects were associated with germ cell development, spermatid development and differentiation, and sperm motility. By PND25, the Akt1 gene-environment interaction had pronounced effects on genes associated with Sertoli cell (SC) differentiation and claudin-associated junctional formation suggesting delayed formation of the blood-testis barrier (BTB). To confirm these observations, biotin tracer experiments demonstrated a permeable blood-testis barrier in PTU-exposed PKBalpha/Akt1-/- tubules as late as PND25 compared to PTU-exposed Akt1+/+ seminiferous tubules. Transmission electron microscopy demonstrated altered SC morphology, aberrant SC localization, and disorganized actin bundle formation. Taken together, loss of Akt1 coupled with postnatal exposure to the neonatal goitrogen, PTU, in the testis contributes to a transcriptional profile associated with impaired integrity of the blood-testis barrier. In summary, the Akt1-/- mouse represents a potentially important model to study BTB formation and reassembly in response to male reproductive toxicants and the various signaling networks which mediate these responses.
2011-09-04 | GSE28664 | GEO
Project description:Akt1 plays a protective role in the postnatal C57BL6 mouse testis following lactational exposure to the neonatal goitrogen, propylthiouracil (PTU). To elucidate the transcriptional profile mediating this phenotypic effect, we monitored changes in testicular gene expression at postnatal days (PNDs) 15 and 25 in Akt1+/+, Akt1+/-, and Akt1-/- testes following exposure to 0.01% PTU allowing us to determine changes in gene expression due to 1.) genotype effects; 2.) exposure effects; and 3.) genotype-by-exposure interactions. Early PTU-dependent gene changes included genes involved in lipid metabolism, spermatid differentiation, meiosis and adhesion. Early Akt1-dependent effects were associated with germ cell development, spermatid development and differentiation, and sperm motility. By PND25, the Akt1 gene-environment interaction had pronounced effects on genes associated with Sertoli cell (SC) differentiation and claudin-associated junctional formation suggesting delayed formation of the blood-testis barrier (BTB). To confirm these observations, biotin tracer experiments demonstrated a permeable blood-testis barrier in PTU-exposed PKB/Akt1-/- tubules as late as PND25 compared to PTU-exposed Akt1+/+ seminiferous tubules. Transmission electron microscopy demonstrated altered SC morphology, aberrant SC localization, and disorganized actin bundle formation. Taken together, loss of Akt1 coupled with postnatal exposure to the neonatal goitrogen, PTU, in the testis contributes to a transcriptional profile associated with impaired integrity of the blood-testis barrier. In summary, the Akt1-/- mouse represents a potentially important model to study BTB formation and reassembly in response to male reproductive toxicants and the various signaling networks which mediate these responses. The microarray analysis employed a balanced factorial design, with one chip created for each of three mice under each experimental condition: mouse genotype (Akt1+/+, Akt1+/-, and Akt1-/-), exposure (PTU and Control), and age (sacrificed at PND15 and 25), with a total of 36 mice and 36 chips. MoGene 1.0 st v1 arrays were used for the samples from PND 15 and Mouse Genome 430 2.0 arrays were used for the samples from PND 25. One chip, PTU-exposed, Akt1-/-, PND25, was determined to not be of high quality and was not included in the analysis or provided here.
2011-09-03 | E-GEOD-28664 | biostudies-arrayexpress
Project description:Reproductive capacity can be altered by challenges experienced during critical periods of development, including fetal development and early neonatal life. Gossypol is a polyphenolic compound, commonly found in seeds of cotton plants, that impairs male reproduction. In this study, we investigated whether the exposure to gossypol in utero and during lactation alters testis development and testis gene expression in sheep.
2019-07-04 | GSE133811 | GEO
Project description:We investigated if a serum microRNA signatured correlated with the presence of thyroid-mediated developmental neurotoxicity in the rat. We isolated serum from control (euthyroid) and exposed (hypothyroid) rat pups on PN8. The maternal exposure utilized to induce developmental hypothyroidism was propylthiouracil (PTU). PTU was administered in the drinking water during pregnancy and lactation.
2024-09-03 | GSE240066 | GEO
Project description:An excess in thyroid hormone during rodent neonatal life causes abnormal prolifration and maturation of testicular cells, leading to reduced testis size and impairments in steroidogenesis, Sertoli cell function, spermatogenesis and fertility. The high expression of type 3 deiodinase in the neonatal testis protects this tissue from premature exposure to thyroid hormones, since this gene (Dio3) function is to degrade thyroid hormones. DIO3-deficient mice (Dio3KO) exhibit a marked reduction in Sertoli cell proliferation and testis size, abnormalities in the reproductive axis and impaired fertility (Martinez et al. 2016, Endocrinology157:1276). To identify genes that are untimely regulated by thyroid hormone in the developing testes, we have performed RNAseq in testis total RNA from wild type and DIO3KO mouse neonates.
2019-08-01 | GSE117157 | GEO
Project description:Here, we aimed to apply a TMT based quantitative phosphoproteomics approach to investigate rodent thyroid toxicity. For this purpose, male Wistar rats have been exposed to a direct (6-propyl-2-thiouracil, PTU) and an indirect (phenytoin) thyroid toxicant, respectively. Thereby, two doses (low:5ppm for PTU and 300ppm for phenytoin , high: 50ppm for PTU and 2400ppm for phenytoin) and three exposure time phase (short: 2 weeks, long:4 weeks, and long+recovery: 4weeks+2weeks) were investigated, allowing insights into the modes of action during thyroid toxicity. Phosphoproteomics were applied to liver.
2024-10-25 | PXD030254 | Pride
Project description:We report that the DNA methylation profile of a child’s neonatal whole blood can be significantly influenced by his or her mother’s neonatal blood lead levels (BLL). We recruited 35 mother-infant pairs in Detroit and measured the whole blood lead (Pb) levels and DNA methylation levels at over 450,000 loci from current blood and neonatal blood from both the mother and the child. We found that mothers with high neonatal BLL correlate with altered DNA methylation at 564 loci in their children’s neonatal blood. Our results suggest that Pb exposure during pregnancy affects the DNA methylation status of the fetal germ cells, which leads to altered DNA methylation in grandchildren’s neonatal dried blood spots. This is the first demonstration that an environmental exposure in pregnant mothers can have an epigenetic effect on the DNA methylation pattern in the grandchildren.
2015-04-01 | GSE67444 | GEO
Project description:Sperm develop in the seminiferous tubules of the testis from puberty, sequestered inside the blood-testis barrier to prevent their recognition as “non-self” by the immune system. It is widely assumed that proteins expressed specifically in sperm do not have direct access to the circulation or the immune system. This assumption underlies the pursuit of cancer testis antigens (CTAs) as therapeutic targets and biomarkers for particular cancers. CTAs are aberrantly expressed in cancer but only expressed in sperm in healthy men; thus these proteins are assumed to be absent from the blood and/or to be neoantigens.
2021-04-01 | PXD014333 | Pride
Project description:Establishing And Maintaining The Blood-Brain Barrier: Epigenetic And Signaling Determinants
| PRJNA1143537 | ENA