scholarly journals In-vitro steroid synthesis by the placenta of cows in late gestation and at parturition

Reproduction ◽  
1988 ◽  
Vol 83 (2) ◽  
pp. 565-573 ◽  
Author(s):  
T. S. Gross ◽  
W. F. Williams
Keyword(s):  
Late Gestation ◽  
Steroid Synthesis

IN VITRO STEROID SYNTHESIS BY FOETAL RABBIT ADRENALS

1971 ◽  
Vol 68 (2) ◽  
pp. 209-218 ◽  
Author(s):  
K. Kurachi ◽  
M. Miyazaki ◽  
H. Mori ◽  
K. Matsumoto
Keyword(s):  
Isotope Dilution ◽  
Hydroxysteroid Dehydrogenase ◽  
Late Gestation ◽  
Cortical Tissue ◽  
Steroid Synthesis ◽  
Metabolic Pattern ◽  
Adrenal Tissue ◽  
Tissue Homogenates

ABSTRACT Adrenal tissue homogenates from foetal rabbits in late gestation and their mothers were incubated with [7α-3H] pregnenolone and analyzed for conversion products by reverse isotope dilution procedures. Deoxycorticosterone and corticosterone were synthesized as main products by foetal as well as by adult adrenals. In addition, small amounts of progesterone, 17-hydroxypregnenolone and cortisol were formed by both adrenals. No C19-steroids and 16α-hydroxysteroids could be found. The results indicate a similarity in the qualitative metabolic pattern of pregnenolone by adrenal cortical tissue of late gestation rabbit foetuses to that of adult rabbits. However, the activity of 3β-hydroxysteroid dehydrogenase per gram tissue in the foetal rabbit adrenal was of the order of one tenth that in the adrenals of their mothers. By using [3H] progesterone as substrate, the activities of 21-hydroxylase and 11β-hydroxylase in the foetal adrenal were similarly demonstrated to be less than that of the adrenal of the mother.

Decreases in ovine fetal cartilage sulfate uptake and serum sulfate during gestation

1985 ◽  
Vol 249 (1) ◽  
pp. E115-E120
Author(s):  
F. H. Morriss ◽  
R. N. Marshall ◽  
S. S. Crandell ◽  
B. J. Fitzgerald ◽  
L. Riddle
Keyword(s):  
Human Serum ◽  
Costal Cartilage ◽  
Full Term ◽  
Late Gestation ◽  
In Vitro Assays ◽  
Sulfate Uptake ◽  
Fetal Sheep ◽  
Ovine Fetal ◽  
Serum Sulfate

In vitro assays for [35S]sulfate uptake by ovine fetal costal cartilage were used to assess gestational changes in cartilage metabolism. Addition of 20% normal human serum to the incubation medium increased fetal cartilage [35S]sulfate incorporation into glycosaminoglycans. Both basal and human serum-stimulated uptakes of [35S]sulfate by fetal sheep cartilage decreased from midgestation to full term. The incremental response in [35S]sulfate uptake that was stimulated by human serum decreased as gestation proceeded to full-term. Fetal serum sulfate concentration decreased logarithmically during gestation, raising the possibility that cartilage sulfate uptake might become substrate limited as full term is approached. Perfusion of seven late gestation sheep fetuses for 7 days with Na2SO4 to achieve serum sulfate concentrations similar to those observed earlier in gestation resulted in a 33% increase in mean cartilage [35S]sulfate uptake compared with that of control twin fetuses, but uptake was not increased to values that occurred spontaneously earlier in gestation. These results suggest that the decreasing rate of [35S]sulfate uptake by fetal cartilage during the last half of gestation is associated only minimally with decreasing serum sulfate levels and is most consistent with intrinsic change in resting chondrocyte metabolism during gestation.

Effects of Maternal Nutrient Restriction During Gestation on LH Production in the Female Bovine Fetus

2021 ◽  
Vol 99 (Supplement_2) ◽  
pp. 25-26
Author(s):  
Sterling H Fahey ◽  
Sarah West ◽  
John M Long ◽  
Carey Satterfield ◽  
Rodolfo C Cardoso
Keyword(s):  
Protein Content ◽  
Fetal Development ◽  
Monozygotic Twins ◽  
Late Gestation ◽  
Nutrient Restriction ◽  
Western Blots ◽  
Physiological Processes ◽  
Individual Potential ◽  
The Individual

Abstract Gestational nutrient restriction causes epigenetic and phenotypic changes that affect multiple physiological processes in the offspring. Gonadotropes, the cells in the anterior pituitary that secrete luteinizing hormone (LH) and follicle-stimulating hormone (FSH), are particularly sensitive to nutritional changes during fetal development. Our objective herein was to investigate the effects of gestational nutrient restriction on LH protein content and number of gonadotropes in the fetal bovine pituitary. We hypothesized that moderate nutrient restriction during mid to late gestation decreases pituitary LH production, which is associated with a reduced number of gonadotropes. Embryos were produced in vitro with X-bearing semen from a single sire then split to generate monozygotic twins. Each identical twin was transferred to a virgin dam yielding four sets of female twins. At gestational d 158, the dams were randomly assigned into two groups, one fed 100% NRC requirements (control) and the other fed 70% of NRC requirements (restricted) during the last trimester of gestation, ensuring each pair of twins had one twin in each group. At gestational d 265, the fetuses (n = 4/group) were euthanized by barbiturate overdose, and the pituitaries were collected. Western blots were performed using an ovine LH-specific antibody (Dr. A.F. Parlow, NIDDK). The total LH protein content in the pituitary tended to be decreased in the restricted fetuses compared to controls (P < 0.10). However, immunohistochemistry analysis of the pituitary did not reveal any significant changes in the total number of LH-positive cells (control = 460±23 cells/0.5 mm2; restricted = 496±45 cells/0.5 mm2, P = 0.58). In conclusion, while maternal nutrient restriction during gestation resulted in a trend of reduced LH content in the fetal pituitary, immunohistological findings suggest that these changes are likely related to the individual potential of each gonadotrope to produce LH, rather than alterations in cell differentiation during fetal development.

AROMATIZING ACTIVITY OF PLACENTAL MICROSOMAL FRACTIONS FROM EWES IN LATE GESTATION

1975 ◽  
Vol 65 (1) ◽  
pp. 117-125 ◽  
Author(s):  
M. R. MANN ◽  
L. B. CURET ◽  
A. E. COLAS
Keyword(s):  
Sharp Increase ◽  
Enzyme System ◽  
Hydroxysteroid Dehydrogenase ◽  
Relative Increase ◽  
Late Gestation ◽  
Domestic Sheep ◽  
Dramatic Rise ◽  
Oestradiol Production ◽  
Human Placentae

SUMMARY Placental microsomes from eight domestic sheep at 136–146 days of gestation were incubated with radioactive androstenedione, testosterone and dehydroepiandrosterone. Aromatizing activity was examined in the presence and absence of cortisol and the rates of both oestrone and oestradiol synthesis were measured. Oestrone predominated in preference to oestradiol in most of the incubations, a result opposite to that found with human placentae. The sharp increase in the rate of oestradiol production found in the 144- to 146-day-old placentae incubated with testosterone may indicate a more rapid increase of aromatizing than of 17β-hydroxysteroid dehydrogenase activity. The presence of cortisol in the mixtures did not significantly affect the placental aromatizing activity, indicating that there is no direct effect of cortisol on the enzyme system as measured in vitro. The dramatic rise of overall mean aromatizing activity from 4·86 ± 0·22 (s.e.m.) at 138–141 days of gestation to 12·96 ± 0·38 pmol/mg protein/min at 144–146 days (with a greater relative increase in the rate of oestradiol formation), suggests that changes in placental aromatizing activity may play an important role in maternal and foetal plasma oestrogen surges before ovine parturition.

Cyclooxygenase-2 plays a significant role in regulating the tone of the fetal lamb ductus arteriosus

1999 ◽  
Vol 276 (3) ◽  
pp. R913-R921 ◽  
Author(s):  
Ronald I. Clyman ◽  
Pierre Hardy ◽  
Nahid Waleh ◽  
Yao Qi Chen ◽  
Françoise Mauray ◽  
...  
Keyword(s):  
Significant Role ◽  
Ductus Arteriosus ◽  
Late Gestation ◽  
Relative Contribution ◽  
Cox Inhibitor ◽  
Fetal Lamb ◽  
Cox 2 ◽  
Cox 2 Inhibitors ◽  
Cox 1

Nonselective cyclooxygenase (COX) inhibitors are potent tocolytic agents but have adverse effects on the fetal ductus arteriosus. We hypothesized that COX-2 inhibitors may not affect the ductus if the predominant COX isoform is COX-1. To examine this hypothesis, we used ductus arteriosus obtained from late-gestation fetal lambs. In contrast to our hypothesis, fetal lamb ductus arteriosus expressed both COX-1- and COX-2-immunoreactive protein (by Western analysis). Although COX-1 was found in both endothelial and smooth muscle cells, COX-2 was found only in the endothelial cells lining the ductus lumen (by immunohistochemistry). The relative contribution of COX-1 and COX-2 to PGE2 synthesis was consistent with the immunohistochemical results: in the intact ductus, PGE2 formation was catalyzed by both COX-1 and COX-2 in equivalent proportions; in the endothelium-denuded ductus, COX-2 no longer played a significant role in PGE2 synthesis. NS-398, a selective inhibitor of COX-2, was 66% as effective as the selective COX-1 inhibitor valeryl salicylate and the nonselective COX inhibitor indomethacin in causing contraction of the ductus in vitro. At this time, caution should be used when recommending COX-2 inhibitors for use in pregnant women.

scholarly journals Serotonin contributes to high pulmonary vascular tone in a sheep model of persistent pulmonary hypertension of the newborn

2013 ◽  
Vol 304 (12) ◽  
pp. L894-L901 ◽  
Author(s):  
Cassidy Delaney ◽  
Jason Gien ◽  
Gates Roe ◽  
Nicole Isenberg ◽  
Jenai Kailey ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Tryptophan Hydroxylase ◽  
Late Gestation ◽  
Persistent Pulmonary Hypertension ◽  
Sheep Model ◽  
Pulmonary Hemodynamics ◽  
Fetal Sheep ◽  
Pulmonary Arterial

Although past studies demonstrate that altered serotonin (5-HT) signaling is present in adults with idiopathic pulmonary arterial hypertension, whether serotonin contributes to the pathogenesis of persistent pulmonary hypertension of the newborn (PPHN) is unknown. We hypothesized that 5-HT contributes to increased pulmonary vascular resistance (PVR) in a sheep model of PPHN and that selective 5-HT reuptake inhibitor (SSRI) treatment increases PVR in this model. We studied the hemodynamic effects of 5-HT, ketanserin (5-HT2A receptor antagonist), and sertraline, an SSRI, on pulmonary hemodynamics of the late gestation fetal sheep with PPHN caused by prolonged constriction of the ductus arteriosis. Brief intrapulmonary infusions of 5-HT increased PVR from 1.0 ± 0.07 (baseline) to 1.4 ± 0.22 mmHg/ml per minute of treatment ( P < 0.05). Ketanserin decreased PVR from 1.1 ± 0.15 (baseline) to 0.82 ± 0.09 mmHg/ml per minute of treatment ( P < 0.05). Sertraline increased PVR from 1.1 ± 0.17 (baseline) to 1.4 ± 0.17 mmHg/ml per minute of treatment ( P = 0.01). In addition, we studied 5-HT production and activity in vitro in experimental PPHN. Compared with controls, pulmonary artery endothelial cells from fetal sheep with PPHN exhibited increased expression of tryptophan hydroxylase 1 and 5-HT production by twofold and 56%, respectively. Compared with controls, 5-HT2A R expression was increased in lung homogenates and pulmonary artery smooth muscle cell lysates by 35% and 32%, respectively. We concluded that increased 5-HT contributes to high PVR in experimental PPHN through activation of the 5-HT2A receptor and that SSRI infusion further increases PVR in this model.

Effects of n-6 polyunsaturated fatty acids on prostaglandin production in ovine fetal chorion cells in vitro in late gestation ewes

Placenta ◽  
2011 ◽  
Vol 32 (10) ◽  
pp. 752-756 ◽  
Author(s):  
Z. Cheng ◽  
M. Elmes ◽  
S. Kirkup ◽  
D.R.E. Abayasekara ◽  
D.C. Wathes
Keyword(s):  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Late Gestation ◽  
Prostaglandin Production ◽  
Ovine Fetal

Adrenal tumors provide insight into the role of cortisol in NK cell activity

2021 ◽  
Author(s):  
Andrew E. Greenstein ◽  
Mouhammed Amir Habra ◽  
Subhagya A. Wadekar ◽  
Andreas Grauer
Keyword(s):  
Immune Response ◽  
Nk Cells ◽  
Cell Activation ◽  
Nk Cell ◽  
Phase 1 ◽  
Cell Activity ◽  
The Cancer Genome Atlas ◽  
Adrenal Tumors ◽  
Steroid Synthesis

Elevated glucocorticoid (GC) activity may limit tumor immune response and immune checkpoint inhibitor (ICI) efficacy. Adrenocortical carcinoma (ACC) provides a unique test case to assess correlates of GC activity, as approximately half of ACC patients exhibit excess GC production (GC+). ACC multi-omics were analyzed to identify molecular consequences of GC+ and assess the rationale for combining the glucocorticoid receptor (GR) antagonist relacorilant with an ICI. GC status, mRNA expression, and DNA mutation and methylation data from 71 adrenal tumors were accessed via The Cancer Genome Atlas. Expression of 858 genes differed significantly between GC- and GC+ ACC cases. KEGG pathway analysis showed higher gene expression of 3 pathways involved in steroid synthesis and secretion in GC+ cases. Fifteen pathways, most related to NK cells and other immune activity, showed lower expression. Hypomethylation was primarily observed in the steroid synthesis pathways. Tumor-infiltrating CD4+ memory (P=.003), CD8+ memory (P=.001), and NKT-cells (P=.014) were depleted in GC+ cases; tumor-associated neutrophils were enriched (P=.001). Given the pronounced differences between GC+ and GC- ACC, the effects of cortisol on NK cells were assessed in vitro (NK cells from human PBMCs stimulated with IL-2 or IL-12/15). Cortisol suppressed, and relacorilant restored, NK cell activation, proliferation, and direct tumor cell killing. Thus, GR antagonism may increase the abundance and function of NK and other immune cells in the tumor microenvironment, promoting immune response in GC+ ACC and other malignancies with GC+. This hypothesis will be tested in a phase 1 trial of relacorilant + ICI.

Abstract 96: Inactivation of Neddylation Causes Left Ventricular Noncompaction Cardiomyopathy Through Suppressing YAP Signaling

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Jianqiu Zou ◽  
Wenxia Ma ◽  
Jie Li ◽  
Rodney Littlejohn ◽  
Il-man Kim ◽  
...  
Keyword(s):  
Cardiac Development ◽  
Heart Diseases ◽  
Left Ventricular ◽  
Late Gestation ◽  
Mouse Heart ◽  
Cardiomyocyte Proliferation ◽  
Transcription Cofactor ◽  
Wild Type Counterpart

Rationale: Cardiac development is orchestrated by a number of growth factors, transcription factors and epigenetic regulators, perturbation of which can lead to congenital heart diseases and cardiomyopathies. However, the role of novel ubiquitin-like protein modifiers, such as NEDD8 (neural precursor cells expressed developmentally downregulated 8), in cardiac development is unknown. Objectives: The objective of this study was to determine the significance of NEDD8 modification (neddylation) during perinatal cardiac development. Methods and Results: Neddylated proteins and NEDD8 enzymes were highly abundant in fetal and neonatal hearts but downregulated in adult hearts. We employed an αMHC Cre transgene to delete NAE1, a subunit of the NEDD8 E1 enzyme, in the perinatal mouse heart. Cardiac-specific deletion of NAE1 (NAE1 CKO ) significantly decreased neddylated proteins in the heart. The NAE1 CKO mice displayed cardiac hypoplasia, ventricular non-compaction and heart failure during late gestation, which became more pronounced by postnatal day 1 and led to perinatal lethality. Mechanistically, genetic deletion or pharmacological inhibition of NAE1 resulted in accumulation of Hippo kinases Mst1 and LATS1/2, which in turn phosphorylated and inactivated YAP, a transcription cofactor necessary for cardiomyocyte proliferation, leading to dysregulation of a number of cell cycle-regulatory genes and blockade of cardiomyocyte proliferation in vivo and in vitro . Reactivation of YAP signaling by overexpression of a constitutively-active YAP mutant (YAP 5SA ), but not its wild-type counterpart, overcame the blockade of cardiomyocyte proliferation induced by inhibition of NAE1. Conclusions: Our findings establish the importance of neddylation in the heart, more specifically, in ventricular chamber maturation, and identify neddylation as a novel regulator of Hippo-YAP signaling to promote cardiomyocyte proliferation.

Abstract 198: Multipotent Placenta-derived Cdx2 Cells Possess in vitro and in vivo Cardiomyogenic Potential

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Sangeetha Vadakke Madathil ◽  
Amaresh Ranjan ◽  
Jesse Yoon ◽  
Joseph Tripodi ◽  
Koen Raedschelders ◽  
...  
Keyword(s):  
Stem Cell ◽  
Proteomic Analysis ◽  
Troponin T ◽  
Embryonic Stem ◽  
Late Gestation ◽  
Cardiac Differentiation ◽  
Homeodomain Protein ◽  
Mhc Molecules ◽  
Junction Protein

Stem cell-based therapies for cardiac regeneration are of crucial importance and an ideal cell-type is yet to be established. We previously reported that fetal cells from placenta “home” to injured maternal heart and approximately 40% (40/100) of the migrating cells expressed homeodomain protein Cdx2. This interesting observation led us to hypothesize that placental Cdx2 could be a novel cell target for cardiac differentiation. To understand this phenomenon, we employed a cre-lox strategy that labeled Cdx2 cells in placenta with e-GFP and induced myocardial infarction (MI) in pregnant mice at mid-gestation. The maternal heart was analyzed 4 weeks post-MI for the presence of Cdx2-eGFP-derived cardiomyocytes. Additionally, Cdx2 cells were isolated from late-gestation placenta and assayed for cardiac differentiation in vitro followed by live cell imaging. Phenotypic and whole-cell proteomic analysis, clonal and vascular lineage differentiation and immune profiling were carried out subsequently. We observed that Cdx2 cells migrated to injured maternal hearts and differentiated into cardiomyocytes highlighting the functional significance of fetal-maternal stem cell transfer. Additionally, isolated Cdx2 cells from the late placenta differentiated into spontaneously beating cardiomyocytes and expressed structural proteins cardiac troponin T(cTnT), α-sarcomeric actinin and gap junction protein Cx43. These cells underwent clonal expansion and differentiated into endothelial and smooth muscle lineages in culture indicative of their multipotent nature. Low expression of MHC molecules and other components of the immune-response, infer that these cells possess the ability to evade host immune surveillance. Proteomic analysis demonstrated that 145 proteins were uniquely identified in the Cdx2 cells compared to embryonic stem cells. These protein networks reflected an increased activation of functions involving migration, fertility, homing, and chemotaxis. Our study is the first to demonstrate that Cdx2 may play a role in cardiac differentiation and delineate multipotent cells in placenta with an inherent “homing” ability. These findings point to a potential role for Cdx2 cells in cardiac regenerative therapies using allogeneic cells.

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