scholarly journals Developmental regulation of corticotrophin receptor gene expression in the adrenal gland of the ovine fetus and newborn lamb: effects of hypoxia during late pregnancy

2001 ◽  
Vol 169 (1) ◽  
pp. 1-10 ◽  
Author(s):  
M Fraser ◽  
GA Braems ◽  
Keyword(s):  
Adrenal Gland ◽  
Receptor Gene ◽  
In Situ Hybridisation ◽  
Adult Life ◽  
Late Pregnancy ◽  
Mrna Levels ◽  
Fetal Sheep ◽  
Altered Expression ◽  
Adult Sheep ◽  
Adrenal Tissue

Responsiveness of the fetal sheep adrenal gland to adrenocorticotrophin (ACTH) increases in late pregnancy, resulting in increased glucocorticoid production. Development of this responsiveness is an important determinant of fetal hypothalamic-pituitary-adrenal function and depends, in part, on the potential for ACTH binding to adrenal tissue. In the present study, we have examined the developmental pattern of ACTH receptor (ACTH-R) expression during the latter half of pregnancy and in neonatal and adult life. As hypoxaemia induces increases in cortisol and ACTH secretion, in addition to increasing fetal adrenal responsiveness, a further aim of this study was to investigate whether hypoxaemia was associated with altered expression of the ACTH-R gene. Whole adrenal glands were removed from fetal sheep, lambs and adult sheep at different stages of development for measurement of ACTH-R mRNA. Moderate hypoxaemia was induced for 48 h beginning on days 124-128, or on days 132-134 of gestation, by decreasing the maternal fractional inspired oxygen. ACTH-R mRNA was detected by northern blotting using a cDNA cloned in our laboratory and by in situ hybridisation. ACTH-R mRNA (3.6 kb major transcript) was detected in adrenal tissue at day 63 of gestation. Its relative abundance increased significantly (P<0.05) between days 126-128 and 140-141 of pregnancy, increased further with the onset of spontaneous labour, and remained increased in newborn lambs at 7 h-7 days after birth. ACTH-R mRNA levels then decreased in adrenal tissue from lambs and adult sheep (P<0.05). Hypoxaemia for 48 h significantly increased ACTH-R mRNA expression in adrenals of the older fetuses (days 134-136) compared with that in controls (P<0.05), but was without effect in younger fetuses. We conclude that levels of ACTH-R mRNA in the fetal adrenal gland increase as term approaches, coincident with the endogenous prepartum surge in plasma ACTH and cortisol. Sustained hypoxaemia resulted in an upregulation of mRNA encoding for ACTH-R, but only in older fetuses and in association with a sustained increase in plasma cortisol. These results are consistent with cortisol, ACTH, or both, contributing to increased fetal adrenal responsiveness, by increasing expression of fetal adrenal receptors for ACTH.

Developmental regulation of preproenkephalin (PENK) gene expression in the adrenal gland of the ovine fetus and newborn lamb: effects of hypoxemia and exogenous cortisol infusion

1997 ◽  
Vol 155 (1) ◽  
pp. 143-149 ◽  
Author(s):  
M Fraser ◽  
SG Matthews ◽  
G Braems ◽  
T Jeffray ◽  
Keyword(s):  
Gene Expression ◽  
Adrenal Gland ◽  
Plasma Cortisol ◽  
Late Gestation ◽  
Mrna Levels ◽  
Fetal Sheep ◽  
Adult Sheep ◽  
Organ Systems ◽  
Response To Stress ◽  
In Pregnancy

Development of the fetal adrenal gland is crucial not only for maturation of several fetal organ systems and the initiation of parturition, but also for the development of the fetal response to stress. The enkephalin-related peptides are present in the chromaffin cells of the fetal adrenal medulla and are secreted in response to stress and with sympathetic stimulation. However, changes in expression of preproenkephalin (PENK) with gestation and in response to stress have not been studied in detail. Therefore we examined the developmental pattern of PENK gene expression in the adrenal gland of fetal and newborn lambs, and of adult sheep. We also determined whether levels of PENK mRNA in the fetal adrenal gland changed in response to exogenous glucocorticoids in late gestation, or in response to hypoxemia. Adrenal glands were removed from fetal sheep, lambs and adult sheep at different stages of development for measurement of PENK mRNA. Cortisol was infused (5 micrograms/min) for 12, 24 or 96 h beginning on day 124-129 of gestation. Moderate hypoxemia was induced for 48 h beginning on day 126-130, or at day 134-136 of gestation, by lowering the maternal fractional inspired oxygen. At the end of the treatment periods, the ewes and fetuses were euthanized. Adrenal PENK mRNA were measured by Northern blot analysis. PENK mRNA levels in fetal adrenals were significantly higher (P < 0.05) on days 140-141 of gestation than earlier in pregnancy, and then decreased significantly with the onset of parturition (days 142-146). After cortisol infusion to the fetus for 96 h there was a significant reduction in adrenal PENK mRNA levels. Hypoxemia resulted in a significant increase in PENK mRNA levels in fetuses at day 126-130 of gestation, but not at the later time in pregnancy when endogenous plasma cortisol concentrations were higher. We conclude that there is a decrease in levels of PENK mRNA in the fetal adrenal gland before parturition at the time of the endogenous prepartum rise in plasma cortisol. Hypoxemia led to an elevation of PENK mRNA levels in fetuses at less than 130 days, but after that time, when the basal and stimulated cortisol responses had risen, there was no significant effect of hypoxemia on PENK mRNA. Cortisol infusion to the fetus at this stage of pregnancy resulted in a decrease in adrenal PENK mRNA levels. We suggest that cortisol may play an important role in the regulation of fetal adrenal PENK mRNA levels and enkephalin synthesis by the adrenal gland of the fetal sheep.

FSH receptor gene expression during ovarian follicle development in sheep

1995 ◽  
Vol 15 (3) ◽  
pp. 273-281 ◽  
Author(s):  
D J Tisdall ◽  
K Watanabe ◽  
N L Hudson ◽  
P Smith ◽  
K P McNatty
Keyword(s):  
Gene Expression ◽  
Granulosa Cells ◽  
Ovarian Follicle ◽  
Receptor Gene ◽  
Fsh Receptor ◽  
Follicular Growth ◽  
Fetal Sheep ◽  
Adult Sheep ◽  
Receptor Gene Expression ◽  
Fsh Receptor Gene

ABSTRACT A key question in elucidating the role of FSH in ovarian function is to determine when during follicular growth the FSH receptor first appears. The aim of this study was to examine the site and time of FSH receptor gene expression during early follicular growth. This study was carried out on ovaries of adult sheep during the luteal and prostaglandin-induced follicular phase of the oestrous cycle and also on ovaries of fetal sheep at 90, 100, 120 and 135 days of gestation (term=day 147). Using reverse transcription-PCR and a set of PCR primers spanning exons 8/9/10, two partial FSH receptor cDNAs (500 and 310 bp) were isolated from adult sheep ovary. It was shown by sequencing that exon 8 was deleted in the 310 bp cDNA, implying that this was part of an alternatively spliced FSH receptor transcript. Using RNA in situ hybridisation on ovaries of adult sheep, FSH receptor mRNA was observed in granulosa cells of early preantral follicles with one to two cell layers and it was seen that gene expression continued throughout folliculogenesis into advanced stages of atresia. Moreover, in the fetus, FSH receptor gene expression was detected in follicles with two or more layers of granulosa cells in ovaries taken at 100, 120 and 135 days of gestation. These results suggest that the FSH receptor gene is expressed after the granulosa cells of a folllicle have begun to divide but not during the earliest stages of follicle growth, namely the transformation of a primordial follicle to a primary follicle.

Opposite effects of glucocorticoid on hepatic 11 β-hydroxysteroid dehydrogenase mRNA and activity in fetal and adult sheep

1994 ◽  
Vol 143 (1) ◽  
pp. 121-126 ◽  
Author(s):  
K Yang ◽  
E T M Berdusco ◽  
J R G Challis
Keyword(s):  
Gene Expression ◽  
Fetal Liver ◽  
Reductase Activity ◽  
Mrna Level ◽  
Hydroxysteroid Dehydrogenase ◽  
Fetal Life ◽  
Mrna Levels ◽  
Fetal Sheep ◽  
Adult Sheep ◽  
Hepatic Level

Abstract The level of 11 β-hydroxysteroid dehydrogenase (11β-HSD) mRNA in the fetal sheep liver increases dramatically between day 130 and term (term=day 145), but the causal factors remain unknown. The present study was designed to determine the effects of exogenous glucocorticoid on the fetal hepatic 11 β-HSD gene expression. Dexamethasone (dex; 2 μg/min over 15 min every 2 h) or saline was infused into chronically-catheterized fetal sheep at day 130 of gestation for 4 days. At the end of infusion, the lower right lobe of the liver was collected, total cellular RNA extracted and subjected to Northern blot analysis. It was found that the level of the hepatic 11 β-HSD mRNA in dex-treated fetuses was about four times higher than that in the saline-treated controls. To examine whether changes occur in the response of hepatic 11 β-HSD gene expression to glucocorticoids in adulthood, we also treated non-pregnant ewes with dex (10 mg/day) for 4 days. By contrast, this treatment regime in adult sheep produced a small but significant decrease in hepatic 11 β-HSD mRNA levels. We also determined whether age-specific changes in the hepatic level of 11 β-HSD mRNA following dex treatment were reflected in the level of 11 β-HSD enzyme activity. Hepatic 11 β-HSD activity was determined by a standard in vitro conversion assay using cortisol and cortisone as physiological substrates. In both fetal and adult livers, 11-oxoreductase activity (cortisone→cortisol) was predominant. Following dex treatment, there was a significant increase in the fetal hepatic level of both 11β-dehydrogenase (cortisol→cortisone) and 11-oxoreductase activities. Furthermore, the C-11 activation index, an indicator of glucocorticoid net gain, was also increased in the fetal liver by dex. In marked contrast, dex treatment in the adult did not alter the C-11 activation index though it produced a significant decrease in the hepatic level of both 11 β-dehydrogenase and reductase activities. In summary, these results indicate that (1) exogenous glucocorticoid exerts opposite effects on hepatic 11 β-HSD gene expression in fetal and adult sheep; (2) dex-induced age-specific changes in the level of 11β-HSD mRNA are carried though to the level of 11β-HSD protein; and (3) since 11 β-HSD reductase activity is predominant in both fetal and adult sheep livers, the liver may be a potential extra-adrenal source of cortisol. Furthermore, we speculate that (1) the dramatic increase in the fetal hepatic 11 β-HSD mRNA level at term may be due to the elevated fetal plasma concentration of glucocorticoid; and (2) glucocorticoid-induced increases in the fetal hepatic 11β-HSD gene expression and the resultant increase in the C-11 activation index during the last days of fetal life may play a crucial role in fetal organ maturation and in the endocrine mechanisms leading to parturition. Journal of Endocrinology (1994) 143, 121–126

scholarly journals The usefulness of competitive PCR: airway gene expression of IL-5, IL-4, IL-4δ2, IL-2, and IFNγ in asthma

Thorax ◽  
2001 ◽  
Vol 56 (7) ◽  
pp. 541-548
Author(s):  
E M Glare ◽  
M Divjak ◽  
M J Bailey ◽  
E H Walters
Keyword(s):  
Gene Expression ◽  
Inhaled Corticosteroids ◽  
In Situ Hybridisation ◽  
Housekeeping Gene ◽  
Cross Sectional Study ◽  
Mrna Levels ◽  
Competitive Pcr ◽  
Cross Sectional ◽  
Steroid Use ◽  
Biopsy Specimens

BACKGROUNDAsthma has been described as an eosinophilic bronchitis driven by interleukin(IL)-4 and IL-5. The quantification of cytokine mRNA levels in airway samples has been confounded by housekeeping gene expression which differs between and within asthmatics and controls.METHODSThe usefulness of competitive reverse transcriptase-polymerase chain reaction (RT-PCR) that is independent of housekeeping gene expression for quantitating the mRNA for interferon (IFN)γ, IL-2, IL-5, IL-4 and its receptor antagonist encoding splicing variant IL-4δ2 was determined in a cross sectional study of 45 normal control subjects and 111 with asthma.RESULTSAtopic controls and atopic asthmatic subjects expressed more IL-5 than non-atopic controls (p<0.02) in bronchoalveolar lavage (BAL) cells, but not in biopsy specimens. IL-5 mRNA expression in BAL cells from asthmatic subjects using inhaled corticosteroids (ICS) was significantly lower than those not receiving ICS (p=0.04). IL-2 mRNA levels differed with steroid use in biopsy specimens but not in BAL cells. IFNγ, IL-4, and IL-4δ2 mRNA levels did not differ between any groups and were not affected by steroid use. IL-4 and IL-4δ2 mRNA levels were positively correlated (p<0.0001), suggesting coordinated transcription.CONCLUSIONSWhile the signal differentiation of competitive PCR in asthma may rival that of in situ hybridisation and immunohistochemistry, the method is expensive and wasteful of material.

scholarly journals Age-related decline in the expression of GDF9 and BMP15 genes in follicle fluid and granulosa cells derived from poor ovarian responders

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yan Gong ◽  
Jesse Li-Ling ◽  
Dongsheng Xiong ◽  
Jiajing Wei ◽  
Taiqing Zhong ◽  
...  
Keyword(s):  
Granulosa Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mrna Levels ◽  
Clinical Trial Registry ◽  
Altered Expression ◽  
Vitro Fertilization ◽  
Age Related ◽  
Tertiary Teaching ◽  
Poor Ovarian Responders

Abstract Background Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) genes play important roles in folliculogenesis. Altered expression of the two have been found among patients with poor ovarian response (POR). In this prospective cohort study, we have determined the expression of the GDF9 and BMP15 genes in follicle fluid (FF) and granulosa cells (GCs) derived from poor ovarian responders grouped by age, and explored its correlation with the outcome of in vitro fertilization and embryo transfer (IVF-ET) treatment. Methods A total of 196 patients with POR were enrolled from a tertiary teaching hospital. The patients were diagnosed by the Bologna criteria and sub-divided into group A (< 35 year old), group B (35–40 year old), and group C (> 40 year old). A GnRH antagonist protocol was conducted for all patients, and FF and GCs were collected after oocyte retrieval. Expression of the GDF9 and BMP15 genes in the FF and GCs was determined with enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Results Compared with group C, groups A and B had significantly more two pronuclei (2PN) oocytes and transplantable embryos, in addition with higher rates of implantation and clinical pregnancy (P <  0.05). The expression level of GDF9 and BMP15 genes in the FF and GCs differed significantly among the three groups (P <  0.05), showing a trend of decline along with age. The ratio of GDF9/BMP15 mRNA levels were similar among the three groups (P > 0.05). The relative levels of GDF9 and BMP15 proteins in GCs have correlated with the relative mRNA levels in GCs and protein concentrations in FF (P <  0.05). Conclusions For poor ovarian responders, in particular those over 40, the expression of GDF9 and BMP15 is declined along with increased age and in accompany with poorer oocyte quality and IVF outcome, whilst the ratio of GDF9/BMP15 mRNA levels remained relatively constant. Trial registration Chinese Clinical Trial Registry Center (ChiCTR1800016107). Registered on 11 May 2018.

On the origin of dehydroepiandrosterone sulphate in the blood of fetal sheep

1985 ◽  
Vol 104 (2) ◽  
pp. 279-283 ◽  
Author(s):  
G. C. Liggins ◽  
J.-C. Schellenberg ◽  
F. Amato ◽  
B. Godfrey ◽  
R. F. Seamark
Keyword(s):  
Significant Contribution ◽  
Late Pregnancy ◽  
Dehydroepiandrosterone Sulphate ◽  
Fetal Sheep ◽  
Intact Group ◽  
The Mean ◽  
Ovine Fetal

ABSTRACT Total sulphoconjugated and unconjugated dehydroepiandrosterone (DHA) and total oestrone were measured in plasma of intact sheep fetuses, fetuses hypophysectomized at 104–112 days and fetuses bilaterally adrenalectomized at 98–101 days. At 120–127 days, the mean concentrations of total DHA and oestrone in intact fetuses (n = 13) were 29·7 ± 4·2 (s.e.m.) nmol/l and 14·3 ± 2·8 nmol/l respectively. At term, the values for total DHA and oestrone in hypophysectomized fetuses (n = 13) of 18·0 ± 1·9 nmol/l and 9·1 ±2·0 nmol/l were significantly (P <0·05) lower than the intact group whereas in the adrenalectomized fetuses (n = 8) total DHA (80·8±13·0 nmol/l) was higher (P < 0·05) and total oestrone values were similar to the intact animals. Intrafetal infusion of cortisol at term (1 mg/h for 84 h) raised levels of total oestrone in intact (n = 6; 12·3 ± 2·9 vs 31·6± 8·5 nmol/l) and adrenalectomized (n = 4; 14·2 ± 2·6 vs 190·6 ± 53·0 nmol/l) fetuses and of total DHA in hypophysectomized fetuses (n = 7; 16·0±1·9 vs 31·6 ± 8·5 nmol/l) while infusion of ACTH(1–24) (5 μg/h) was without significant effect in any group. It is concluded that the ovine fetal adrenal in late pregnancy makes no significant contribution either to the high circulating concentrations of DHA sulphate or to the substrates for placental oestrogen synthesis. J. Endocr. (1985) 104, 279–283

Ontogeny of the insulin response to glucose in fetal and adult sheep

1989 ◽  
Vol 67 (10) ◽  
pp. 1288-1293 ◽  
Author(s):  
Pamela E. Houghton ◽  
Thomas J. McDonald ◽  
John R. G. Challis
Keyword(s):  
Time Course ◽  
Bolus Injection ◽  
Peak Plasma ◽  
Femoral Vein ◽  
Insulin Response ◽  
Similar Time ◽  
Fetal Sheep ◽  
Adult Sheep ◽  
Glucose Ratio ◽  
Insulin Response To Glucose

The purpose of the present experiments was to examine in sheep whether the fetal insulin response to glucose was present by day 110 (d110) of pregnancy and whether the magnitude of the fetal insulin response changed between d110 and d145 (term). We also compared the responses observed in fetuses to those of adult nonpregnant sheep. Basal concentrations of glucose measured in plasma collected from the fetal femoral artery rose progressively between d110 and d145 of gestation, but did not attain the plasma glucose concentrations measured in adult sheep. Peak glucose concentrations in fetuses were achieved 10 min following the bolus injection of glucose (0.8 g/kg estimated fetal body weight) into the fetal femoral vein, and peak values increased with gestational age. Significantly higher peak glucose concentrations were achieved in adult sheep. The concentration of insulin rose rapidly in fetuses at d110, and a similar time course of insulin release in plasma was seen at all gestational ages. The peak plasma insulin concentrations were achieved at 20 min and were significantly greater in older (d140–145) than younger (d125–130) fetuses (p < 0.05). Peak insulin values in fetuses were much less than in adult sheep. In adult sheep glucose and insulin concentrations remained elevated at 120 min following the injection of glucose, whereas in the fetus the concentration of insulin had returned to preinjection values by 60 min. The insulin/glucose ratio did not change in fetal lambs over the last one third of gestation and was not different from the adult sheep. We conclude that (1) the fetal insulin response to an acute glucose load is present by d110 of gestation, and (2) the ratio of insulin released per unit glucose elevation did not change in fetal sheep over the last one third of gestation, nor between fetal and adult sheep.Key words: glucose, insulin, fetal sheep.

scholarly journals Characterization and Regulation of Type A Endothelin Receptor Gene Expression in Bovine Luteal Cell Types

Endocrinology ◽  
1999 ◽  
Vol 140 (5) ◽  
pp. 2110-2116 ◽  
Author(s):  
Roni Mamluk ◽  
Nitzan Levy ◽  
Bo Rueda ◽  
John S. Davis ◽  
Rina Meidan
Keyword(s):  
Gene Expression ◽  
Receptor Gene ◽  
Cell Types ◽  
Cell Populations ◽  
Mrna Levels ◽  
Factor I ◽  
Receptor Mrna ◽  
Progesterone Production ◽  
Eta Receptor ◽  
Receptor Gene Expression

Abstract Our previous studies demonstrated that endothelin-1 (ET-1), a 21-amino acid vasoconstrictor peptide, has a paracrine regulatory role in bovine corpus luteum (CL). The peptide is produced within the gland where it inhibits progesterone production by acting via the selective type A endothelin (ETA) receptors. The present study was designed to characterize ETA receptor gene expression in different ovarian cell types and its hormonal regulation. ETA receptor messenger RNA (mRNA) levels were high in follicular cells as well as in CL during luteal regression. At this latter stage, high ETA receptor expression concurred with low prostaglandin F2α receptor mRNA. The ETA receptor gene was expressed by all three major cell populations of the bovine CL; i.e. small and large luteal cells, as well as in luteal endothelial cells. Among these various cell populations, the highest ETA receptor mRNA levels were found in endothelial cells. cAMP elevating agents, forskolin and LH, suppressed ETA receptor mRNA expression in luteinized theca cells (LTC). This inhibition was dose dependent and was evident already after 24 h of incubation. In luteinized granulosa cells (LGC), 10 and 100 ng/ml of insulin-like growth factor I and insulin (only at a concentration of 2000 ng/ml) markedly decreased ETA receptor mRNA levels. In both LGC and LTC there was an inverse relationship between ETA receptor gene expression and progesterone production; insulin (in LGC) and forskolin (in LTC) enhanced progesterone production while inhibiting ETA receptor mRNA levels. Our findings may therefore suggest that, during early stages of luteinization when peak levels of both LH and insulin-like growth factor I exist, the expression of ETA receptors in the gland are suppressed. This study demonstrates physiologically relevant regulatory mechanisms controlling ETA receptor gene expression and further supports the inhibitory role of ET-1 in CL function.

Abstract 107: Mir-431 as a Potential Master Regulator in Angiotensin Ii-induced Vascular Injury

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Kugeng Huo ◽  
Tlili Barhoumi ◽  
Julio C Fraulob-Aquino ◽  
Chantal Richer ◽  
Mathieu Lajoie ◽  
...  
Keyword(s):  
Vascular Injury ◽  
Molecular Networks ◽  
Type I ◽  
Mirna Cluster ◽  
Mrna Levels ◽  
Ang Ii ◽  
Master Regulator ◽  
Developmental Processes ◽  
Altered Expression ◽  
Total Rna

Objective: Vascular injury is an early manifestation and a cause of end-organ damage in hypertension. microRNAs (miRNAs) play an important role in cardiovascular disease, but their implication in vascular injury is remains unclear. We aim to use RNA sequencing (seq) and a systems biology approach to identify master regulators that mediate global gene expression changes in the course of vascular injury. Methods and Results: Ten week-old male C57BL/6 mice were infused or not with angiotensin (Ang) II (1 μg/kg/min, SC) for 14 days. Blood pressure (BP) was measured by telemetry. Total RNA was extracted from the mesenteric vasculature for total RNA and small RNA-seq. Differentially expressed (DE) miRNAs (23 up and 12 down) and mRNAs (550 up and 256 down) were identified (1.5-fold, q <0.05). Molecular networks were constructed to integrate predicted interactions between DE miRNAs and inversely expressed DE mRNAs and between DE transcription factors (TF) and DE genes. Gene enrichment analysis revealed DE mRNAs involved in extracellular matrix (ECM) and developmental processes regulated by DE miRNAs ( q <1.5E-11). Seventeen upregulated miRNAs are located in the miRNA cluster of the Dlk1-Dio3 region that is highly conserved in humans, 9 of which had expression levels correlated with BP ( P <0.05). Among those 9, miR-431 that ranked first as DE miRNA ( q <0.0005) and is 100% conserved in humans, and a conserved putative DE target, a BP-correlated ( P <0.05) TF ETS homologous factor ( Ehf ), which regulates numerous ECM genes including collagen type I α1 ( Col1a1 ), were selected for functional studies. Transfection of a miR-431 mimic in human aortic smooth muscle cells (HASMCs) decreased Ehf (0.1±0.1-fold, P <0.001) and increased Ehf -suppressing target Col1a1 (1.7±0.5-fold, P <0.001) mRNA levels. Transfection of a miR-431 inhibitor caused reciprocal effects ( P <0.05). Ehf siRNA knockdown increased Col1a1 (1.2±0.1-fold, P <0.001) mRNA levels. Conclusions: Ang II infusion altered expression of miRNAs in the Dlk1-Dio3 cluster and genes involved in ECM and developmental processes. miR-431 targets TF Ehf , which leads to increased Col1a1 in HASMCs. miR-431 may act as a master regulator for vascular injury and could be a potential therapeutic target.

Stress Hormone System and Epigenetics in Depression

2017 ◽  
Vol 41 (S1) ◽  
pp. S19-S19
Author(s):  
V. O’Keane ◽  
C. Farrell ◽  
K. Doolin ◽  
J. Chai ◽  
N. O’leary ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Target Genes ◽  
Receptor Gene ◽  
Cell Receptor ◽  
Mrna Levels ◽  
Early Life Adversity ◽  
Generational Transmission ◽  
T Cell Receptor Gene ◽  
Competing Interest ◽  
Hormone System

BackgroundExposure to early life adversity (ELA) has been identified as a major risk factor in the development of major depressive disorder (MDD). It is hypothesized that a mediating mechanism may be environmentally induced alterations in gene function. In our REDEEM (Research in depression: endocrinology, epigenetics and neuroimaging) project we are examining possible epigenetic difference in some previously investigated target genes relevant to depression. To this end, methylation of the following genes were measured: NR3C1 (HPA axis), SLC6A4 (serotonin neurotransmitter function), and CD3ɛ (T cell receptor gene). We also looked at possible trans-generational transmission of epigenetic markers in a mother-baby sample.MethodsDNA was isolated from depressed patients and controls and babies and a portion of the above genes, encompassing our regions of interest, were amplified by PCR. Percentage methylation levels were measured by pyrosequencing. mRNA was also measured for some gene products to see if function was related to methylation. HPA axis function was measured with serial saliva samples throughout the day.Resultsto date: Methylation was increased in the CD3ɛ promoter in depressed subjects relative to controls. In the total group, those exposed to ELA had significantly increased methylation at this site. Levels of CD3ɛ mRNA levels were inversely related to methylation. There were some relationships between maternal ELA and baby methylation at the sites examined.ConclusionsConsistent with an allostatic model of ELA damage, our findings suggest an alteration in epigenetic function in acquired immunity and the HPA axis, mediated by ELA. Findings will be discussed.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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