Malnutrition affects the physiological status and function of pituitary gland in pregnant ewes
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ABSTRACT:
ORGANISM(S): Ovis aries
PROVIDER: GSE220723 | GEO | 2023/11/14
REPOSITORIES: GEO
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Project description:In the current study, five late gestation multiparous ewes were restricted to a 30% feeding level to create a model of malnutrition, while five other ewes were fed normally as controls. All ewes were sacrificed and cecal samples were collected for transcriptome sequencing to study metabolic changes.
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Project description:Transcriptomics and functional bioinformatics were used to investigate the potential interactions of undernutrition and the presence of the conceptus at the time of maternal recognition of pregnancy on uterine indicators of metabolism and reproduction. Adult Rasa Aragonesa ewes were allocated to one of two planes of nutrition during 28 days: maintenance energy intake (control; 5 cyclic, 6 pregnant ewes) providing 7.8 MJ of metabolisable energy per ewe and 0.5 maintenance intake (undernourished; 6 cyclic, 7 pregnant ewes) providing 3.9 MJ of metabolisable energy per ewe. RNA from uterine tissue was harvested at slaughter on day 14 of estrus or pregnancy, and hybridized to the Agilent 15K Sheep Microarray chip. Functional bioinformatics analyses were performed using the Dynamic Impact Approach (DIA) and Ingenuity Pathway Analysis. Among metabolic pathways, citrate cycle, oxidative phosphorylation, pentose and glucuronate interconversions and biosynthesis of unsaturated fatty acids were upregulated in control pregnant compared with control cyclic ewes. However, these pathways were not altered in undernourished ewes. The presence of an embryo in undernourished ewes upregulated fatty acid and glycogenic amino acid metabolism. RIG-I and Toll like receptors and chemokine signaling pathways were upregulated by the presence of the embryo in both control and undernourished ewes, but in the latter group the impact was lower. Undernutrition alone upregulated carbohydrate metabolism, but different pathways were altered in cyclic versus pregnant ewes. Citrate cycle, glycolysis/gluconeogenesis, and pentose and glucuronate interconversions were upregulated in undernourished cyclic compared with control cyclic ewes. Glycolysis/gluconeogenesis, pyruvate and propanoate metabolism, beta-alanine and phenylalanine metabolism were upregulated in undernourished pregnant compared with control pregnant ewes, whereas biosynthesis of unsaturated fatty acids and replication and repair were downregulated. Undernutrition alone led to an overall weak activation of immune system pathways both in cyclic and pregnant ewes. However, undernourished cyclic compared with control cyclic ewes had a high activation of NOD-like and RIG-1 like receptor signaling pathways, whereas undernourished pregnant compared with control pregnant ewes only had a weak upregulation of T cell receptor signaling pathways. Overall, data revealed that metabolic and immune adaptations of the uterus to nutrient restriction are dependent on the presence of the conceptus.
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Project description:POU1F1 regulates, in the pituitary, the development of the prolactin-, growth hormone- and thyrotropin ß-expressing lineages and the expression of these hormone in the mature pituitary through the direct regulation of their promoters. Besides these functions, POU1F1 is also involved in other cellular processes in the pituitary, such as cell division and survival, but the genomic targets involved in these actions are not known. The present ChIP-chip study identified a large number of hitherto unknown potential direct targets that might be involved in these actions, such as Tcf4, Lmo4, Pax6, Trp53 etc.
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Project description:Analysis of gene expression in the pituitary gland of pregnant versus non-pregnant dams. We describe the dynamic control of pituitary gene expression in the pregnant mother, with implications for the regulation of maternal metabolic adaptations to pregnancy.
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Project description:The purpose of this research is to determine whether the drug, Bevacizumab (a monoclonal anti VEGF-A antibody), which is approved to treat patients with metastatic colon cancer induces hyperprolactinemia (increased prolactin secretion) in humans with intact pituitary function. Past studies have shown Bevacizumab to shrink tumor size and also increase prolactin levels. The mechanism of the hyperprolactinemia might be inhibition of pituitary portal vein transport, suggesting that Bevacizumab induces prolactin secretion from normal lactotrophs in the pituitary gland.
Patients who have been treated with Bevacizumab for at least one month will be recruited to participate.
The subjects who are being treated with Bevacizumab by Dr. Stephen Wolin (a sub-investigator) will be screened by him for study eligibility. Dr. Wolin will approach eligible patients with all the information and background of the study and see if they have an interest in being consented.
If consented, there will be 2 blood draws for the research that is not part of their standard care in which 10 ml of blood is collected and prolactin, growth hormone, IGF-I, TSH, thyroxine, ACTH, and cortisol will be measured. One 5ml blood draw will occur before the administration of Bevacizumab and the second 5 ml blood draw will occur after the administration of the Bevacizumab. The investigators will then review the laboratory results. The blood tests are of the hormones of the pituitary gland to test pituitary function and see if there are any abnormalities with the secretions of the gland. Pituitary function abnormalities and hyperprolactinemia are diagnosed by looking at hormone levels in the blood and comparing them to the normal reference ranges.
This study will only involve 10 subjects and will be conducted entirely at Cedars-Sinai Medical Center.
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