scholarly journals Insights into the lipidome and primary metabolome of the uterus from day 14 cyclic and pregnant sheep

2021 ◽  
Author(s):  
Eleanore V O’Neil ◽  
Thomas E Spencer
Keyword(s):  
Early Pregnancy ◽  
Lipid Droplets ◽  
Protein Composition ◽  
Comprehensive Understanding ◽  
Primary Metabolite ◽  
Uterine Lumen ◽  
Lipidomic Analysis ◽  
Esterified Fatty Acids ◽  
Pregnant Sheep ◽  
Phospholipid Classes

Abstract In ruminants, conceptus elongation requires the endometrium and its secretions. The amino acid, carbohydrate, and protein composition of the uterine lumen during early pregnancy has been defined in sheep; however, a comprehensive understanding of metabolomic changes in the uterine lumen is lacking, particularly with respect to lipids. Here, the lipidome and primary metabolome of the uterine lumen, endometrium, and/or conceptus was determined on day 14 of the estrous cycle and pregnancy. Lipid droplets and select triglycerides were depleted in the endometrium of pregnant ewes. In contrast, select ceramides, diglycerides, and non-esterified fatty acids as well as several phospholipid classes (phosphatidylcholine, phosphatidylinositol, phosphatidylglycerols, and diacylglycerols) were elevated in the uterine lumen of pregnant ewes. Lipidomic analysis of the conceptus revealed that triglycerides are particularly abundant within the conceptus. Primary metabolite analyses found elevated amino acids, carbohydrates, and energy substrates, among others, in the uterine lumen of pregnant ewes. Collectively, this study supports the hypothesis that lipids are important components of the uterine lumen that govern conceptus elongation and growth during early pregnancy.

scholarly journals CBIO-05. LIPID METABOLIC REPROGRAMMING SENSITIZES A MOLECULARLY-DEFINED SUBSET OF GLIOBLASTOMAS TO FERROPTOSIS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii16-ii16
Author(s):  
Danielle Morrow ◽  
David Nathanson ◽  
Timothy Cloughesy ◽  
Robert Prins ◽  
Nicholas Bayley ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Lipid Droplets ◽  
Metabolic Reprogramming ◽  
Membrane Phospholipids ◽  
Molecular Alterations ◽  
Lipidomic Analysis ◽  
Novel Association ◽  
Therapeutic Opportunity ◽  
Dependent Cell ◽  
Main Components

Abstract Cancers, including the universally lethal glioblastoma (GBM), have reprogrammed lipid metabolism to fuel tumor growth. However, the molecular alterations responsible for aberrant lipid metabolism, and the potential for identifying new therapeutic opportunities are not fully understood. To systematically investigate the GBM lipidome, we performed integrated transcriptomic, genomic and shotgun lipidomic analysis of an extensive library of molecularly diverse patient-derived GBM samples. Using this comprehensive approach, we discovered two GBM sub-groups defined by their combined molecular and lipidomic profile. Triacylglycerides (TAGs) enriched in polyunsaturated fatty acids (PUFAs) were among the most significantly altered lipids between the two groups of GBM tumors. TAGs are the main components of lipid droplets, which sequester PUFA-TAGs away from membrane phospholipids where their peroxidation can lead to ferroptosis – a regulated from of PUFA-peroxidation dependent cell death. Accordingly, the GBM subgroup with a depletion of PUFA TAGs showed heightened sensitivity to ferroptosis. Our findings suggest a novel association between specific molecular signatures of GBM, lipid metabolism and ferroptosis. This relationship may present a new therapeutic opportunity to target reprogrammed lipid metabolism in a molecularly-defined subset of GBMs.

LIPIDS IN THE MOUSE UTERUS DURING EARLY PREGNANCY

1975 ◽  
Vol 65 (2) ◽  
pp. 233-243 ◽  
Author(s):  
KATHLEEN HALL
Keyword(s):  
Fatty Acids ◽  
Early Pregnancy ◽  
Lipid Droplets ◽  
Time Course ◽  
Post Partum ◽  
Mouse Uterus ◽  
Previous Night ◽  
Decidual Cells ◽  
Glycogen Deposition ◽  
Mitotic Proliferation

SUMMARY Lipids in the uterine endometrium of mice during early pregnancy were investigated by histochemical techniques. Three groups of animals were studied: (1) on days 1–8 inclusive of the first pregnancy, (2) on days 1–9 after mating at the post-partum oestrus and suckling seven or eight young from their first pregnancy, (3) on days 1–6 after delivery of the first litter but with no access to males. Day 1 was that on which a seminal plug appeared in the vagina or (group 3) after birth of a litter during the previous night. In post-partum mice, only the areas between the former implantation sites were studied. Epithelial lipids are sparse during the first 24 h. On day 2 and early day 3 in nulliparous mice, and for a longer period in post-partum mice, the presence of lipid in epithelium and stroma seems mainly a degenerative phenomenon associated with cell breakdown and consequent tissue disruption. During late day 3 and on day 4 the increase in lipid droplets giving staining reactions characteristic for triglycerides may represent the storage in this form of fatty acids no longer needed for phospholipid synthesis or as energy sources, once the intense mitotic proliferation of these cells dies down. Triglycerides also predominated in the necks of the glands, but in the deeper parts, the sparse droplets often gave staining reactions for acidic lipids. In differentiating decidual cells during day 5 and early day 6 in nulliparous mice, histochemical reactions suggest that fatty acids accumulate. Some of these are probably utilized in synthesis of the increasing amounts of phospholipids which were particularly prominent later on day 6 and during day 7, while others appeared to be temporarily stored during that period as triglycerides. The phased deposition and removal of triglyceride proceeds centrifugally through the decidua and is slightly in advance of glycogen deposition and removal in the same cells; its time-course correlated well with that which other workers have described from chemical assay. Histochemical tests appeared to reveal activity of a lipase-esterase (fatty acid ester hydrolase) which strengthened and spread through the decidua in parallel with the disappearance of lipid droplets. In lactating mice, as long as the blastocysts remained in diapause, epithelial lipid resembled that on day 4; in the stromal cells, lipid droplets were plentiful in areas close to the former placental sites but were few or absent elsewhere. Once the delayed implantation had started no abnormalities were detected. Alterations in lipids are discussed in the context of the known changes in the levels of ovarian hormones. Lipids within uterine macrophages are also discussed.

Plasma non-esterified fatty acids in sheep

1960 ◽  
Vol 11 (1) ◽  
pp. 58 ◽  
Author(s):  
EF Annison
Keyword(s):  
Fatty Acids ◽  
Intravenous Injection ◽  
Sharp Rise ◽  
Esterified Fatty Acids ◽  
Pregnant Sheep ◽  
Nefa Level

Concentrations of plasma non-esterified fatty acids (NEFA) in sheep were found to be within the range 0.1–0.9 m-equiv/l. Relatively high levels (1.0–2.5 m-equiv/l) occurred in pregnant and non-pregnant sheep when fasted. Intravenous injection of glucose (1.0 g/kg body wt.) depressed KEFA concentrations to levels of about 0.05 m-equiv/l. Insulin, injected intravenously, caused an initial fall in the NEFA level, followed by a sharp rise which was maintained throughout hypoglycaemia. These results suggest that in sheep, as in many other species, NEBA are of major metabolic importance.

scholarly journals Cortisol and Interferon Tau Regulation of Endometrial Function and Conceptus Development in Female Sheep

Endocrinology ◽  
2012 ◽  
Vol 154 (2) ◽  
pp. 931-941 ◽  
Author(s):  
Piotr Dorniak ◽  
Thomas H. Welsh ◽  
Fuller W. Bazer ◽  
Thomas E. Spencer
Keyword(s):  
Early Pregnancy ◽  
Reductase Activity ◽  
In Utero ◽  
Selective Inhibitor ◽  
Biological Role ◽  
Interferon Tau ◽  
Uterine Lumen ◽  
Conceptus Development ◽  
Female Sheep ◽  
Expression And Activity

During early pregnancy in sheep, the elongating conceptus secretes interferon-τ (IFNT) and the conceptus as well as endometrial epithelia produce prostaglandins (PG) via PG synthase 2 (PTGS2) and cortisol via hydroxysteroid (11-β) dehydrogenase 1 (HSD11B1). Ovarian progesterone induces and PG and IFNT stimulates endometrial HSD11B1 expression and keto-reductase activity as well as many epithelial genes that govern trophectoderm proliferation, migration, and attachment during elongation. The primary aim of these studies was to test the hypothesis that HSD11B1-derived cortisol has a biological role in endometrial function and conceptus development during early pregnancy in sheep. In study 1, cyclic ewes received vehicle, cortisol, PF 915275 (PF; a selective inhibitor of HSD11B1), cortisol and PF, meloxicam (a selective inhibitor of PTGS2), cortisol and meloxicam, recombinant ovine IFNT, or IFNT and PF into the uterus from day 10 to day14 after estrus. Cortisol and IFNT stimulated endometrial HSD11B1 expression and activity, increased endometrial PTGS2 activity and the amount of PG in the uterine lumen, and up-regulated many conceptus elongation-related genes in the endometrium. Some effects of cortisol and IFNT were mediated by PTGS2-derived PG. In study 2, bred ewes received PF 915275 or recombinant ovine IFNT and into the uterus from day 10 to day 14 after mating. Inhibition of HSD11B1 activity in utero prevented conceptus elongation, whereas IFNT rescued conceptus elongation in PF-infused ewes. These results suggest that HSD11B1-derived cortisol mediates, in part, actions of ovarian progesterone and the conceptus on endometrial function and support the hypothesis that IFNT, PG, and cortisol coordinately regulate endometrial functions important for conceptus elongation and implantation during early pregnancy in sheep.

scholarly journals The metabolism of circulating non-esterified fatty acids by the whole animal, hind-limb muscle and uterus of pregnant ewes

1983 ◽  
Vol 49 (1) ◽  
pp. 129-143 ◽  
Author(s):  
D. W. Pethick ◽  
D. B. Lindsay ◽  
P. J. Barker ◽  
A. J. Northrop
Keyword(s):  
Fatty Acids ◽  
Hind Limb ◽  
Ketone Bodies ◽  
Gravid Uterus ◽  
Limb Muscle ◽  
Entry Rate ◽  
Esterified Fatty Acids ◽  
Arterial Concentration ◽  
Pregnant Sheep ◽  
Hind Limb Muscle

1. The over-all and regional metabolism of non-esterified fatty acids (NEFA) was studied using a combination of isotopic and arteriovenous-difference techniques.2. There was a common linear relationship, whether stearic, palmitic or oleic acids were used as tracer, between the arterial NEFA concentration and the rates of entry and oxidation.3. Assuming that the tracer used reflected the metabolism of all the NEFA, the total entry rate in fed and fasted pregnant ewes was (mean±SE) 0·44±0·02 and 0·55±0·07 mmol/h per kg body-weight respectively. Oxidation of NEFA contributed (mean±SE) 34±5 and 58±7% to the respiratory carbon dioxide in fed and fasted animals, this accounting for (mean±SE) 46±6 and 59±3% of the respective entry rates.4. Hind-limb muscle both utilized and produced NEFA. The mean gross fractional extraction (calculated from isotopic uptake) was (mean±SE) 9±1%. Gross utilization of any NEFA and appearance of 14CO2 across the muscle were linearly related to the arterial concentration of tracer fatty acid, irrespective of whether this was oleate or stearate. The amount of 14CO2 appearing was consistent with (mean±SE) 54±8% of the CO2 produced by the hind-limb being derived from NEFA oxidation.5. Infused NEFA were partly converted to ketone bodies. Uptake and oxidation in the hind-limb of ketones formed in the liver could account for approximately 20% of the 14CO2 apparently produced in muscle from NEFA. Correction for this reduces the proportion of CO2 derived from NEFA to 43%. There was some indication that ketones were also produced from NEFA in the hind-limb.6. NEFA were not a significant energy source for the gravid uterus.7. An over-all view of energy sources for the whole animal and for hind-limb muscle in normal and fasted pregnant sheep was presented.

Change in distribution of cytoskeleton-associated proteins, lasp-1 and palladin, during uterine receptivity in the rat endometrium

2018 ◽  
Vol 30 (11) ◽  
pp. 1482 ◽  
Author(s):  
Leigh Nicholson ◽  
Laura Lindsay ◽  
Christopher R. Murphy
Keyword(s):  
Plasma Membrane ◽  
Focal Adhesion ◽  
Early Pregnancy ◽  
Morphological Changes ◽  
Cytoskeletal Proteins ◽  
Initial Contact ◽  
Luminal Epithelium ◽  
Uterine Receptivity ◽  
Uterine Lumen ◽  
Associated Proteins

The epithelium of the uterine lumen is the first point of contact with the blastocyst before implantation. To facilitate pregnancy, these uterine epithelial cells (UECs) undergo morphological changes specific to the receptive uterus. These changes include basal, lateral and apical alterations in the plasma membrane of UECs. This study looked at the cytoskeletal and focal adhesion-associated proteins, lasp-1 and palladin, in the uterus during early pregnancy in the rat. Two palladin isoforms, 140 kDa and 90 kDa, were analysed, with the migration-associated 140-kDa isoform increasing significantly at the time of implantation when compared with the time of fertilisation. Lasp-1 was similarly increased at this time, whilst also being located predominantly apically and laterally in the UECs, suggesting a role in the initial contact between the UECs and the blastocyst. This is the first study to investigate palladin and lasp-1 in the uterine luminal epithelium and suggests an importance for these cytoskeletal proteins in the morphological changes the UECs undergo for pregnancy to occur.

Effects of continuous intravenous infusion of an ovine placental extract enriched in placental lactogen on plasma hormones, metabolites and metabolite biokinetics in non-pregnant sheep

1987 ◽  
Vol 113 (2) ◽  
pp. 277-283 ◽  
Author(s):  
G. Thordarson ◽  
G. H. McDowell ◽  
S. V. Smith ◽  
S. Iley ◽  
I. A. Forsyth
Keyword(s):  
Jugular Vein ◽  
Control Period ◽  
Plasma Concentrations ◽  
Placental Lactogen ◽  
Saline Control ◽  
Irreversible Loss ◽  
Esterified Fatty Acids ◽  
Pregnant Sheep ◽  
Plasma Hormones ◽  
Placental Extract

ABSTRACT Continuous intravenous infusions of saline or of a placental extract containing ovine placental lactogen were given to three non-pregnant, non-lactating ewes over periods of 36 h, 1 week apart. During saline infusion no placental lactogen was detected in jugular vein plasma, but infusion of the placental extract raised the placental lactogen concentration from undetectable to 40-50 μg/l, similar to concentrations in ewes with one fetus on day 90 of pregnancy. By comparison with the saline control period, infusion of the placental extract consistently increased both plasma concentrations and irreversible loss of non-esterified fatty acids. Plasma concentrations of glucose and urea, but not irreversible loss of these metabolites, were consistently increased. Although the placental extract was not subjected to extensive purification, it was enriched in placental lactogen and contained no detectable contamination with insulin, prolactin or growth hormone. The results are suggestive of a role for placental lactogen in modifying metabolism and acting during pregnancy to provide nutrients for fetal metabolism. J. Endocr. (1987) 113, 277–283

Varied effects of doxorubicin (DOX) on the corpus luteum of C57BL/6 mice during early pregnancy

2021 ◽  
Author(s):  
Christian Lee Andersen ◽  
Haeyeun Byun ◽  
Yuehuan Li ◽  
Shuo Xiao ◽  
Doris M Miller ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Corpus Luteum ◽  
Early Pregnancy ◽  
Lipid Droplets ◽  
Luteal Cell ◽  
Knowledge Gap ◽  
Chemotherapeutic Drugs ◽  
Luteal Cells ◽  
Single Intraperitoneal Injection ◽  
Premenopausal Patients

Abstract Certain chemotherapeutic drugs are toxic to ovarian follicles. The corpus luteum (CL) is normally developed from an ovulated follicle for producing progesterone (P4) to support early pregnancy. To fill in the knowledge gap about effects of chemotherapy on the CL, we tested the hypothesis that chemotherapy may target endothelial cells and/or luteal cells in the CL to impair CL function in P4 steroidogenesis using doxorubicin (DOX) as a representative chemotherapeutic drug in mice. In both mixed background mice and C57BL/6 mice, a single intraperitoneal injection of DOX (10 mg/kg) on 0.5 days post coitum (D0.5, post-ovulation) led to ~58% D3.5 mice with serum P4 levels lower than the serum P4 range in the PBS-treated control mice. Further studies in the C57BL/6 ovaries revealed that CLs from DOX-treated mice with low P4 levels had less defined luteal cords and disrupted collagen IV expression pattern, indicating disrupted capillary, accompanied with less differentiated luteal cells that had smaller cytoplasm and reduced StAR expression. DOX-treated ovaries had increased granulosa cell death in the growing follicles, reduced PCNA-positive endothelial cells in the CLs, enlarged lipid droplets and disrupted F-actin in the luteal cells. These novel data suggest that the proliferating endothelial cells in the developing CL may be the primary target of DOX to impair the vascular support for luteal cell differentiation and subsequently P4 steroidogenesis. This study fills in the knowledge gap about the toxic effects of chemotherapy on the CL and provides critical information for risk assessment of chemotherapy in premenopausal patients.

Composition of uterine flushings from Large White and prolific Chinese Meishan gilts

1991 ◽  
Vol 3 (1) ◽  
pp. 51 ◽  
Author(s):  
FW Bazer ◽  
WW Thatcher ◽  
F Matinat-Botte ◽  
M Terqui ◽  
MC Lacroix ◽  
...  
Keyword(s):  
Acid Phosphatase ◽  
Early Pregnancy ◽  
Immunoglobulin A ◽  
Oestrous Cycle ◽  
Large White ◽  
Sodium Potassium ◽  
Uterine Lumen ◽  
Pregnancy Status ◽  
Aminopeptidase P ◽  
Uterine Secretions

This study examined differences in selected components of uterine secretions from Large White and prolific Chinese Meishan gilts during the oestrous cycle or early pregnancy. Total recoverable protein, uteroferrin (measured as acid phosphatase activity), acyl aminopeptidase, calcium, sodium, potassium, immunoglobulins A and G, glucose, fructose, oestradiol-17 beta, and prostaglandins F2 alpha (PGF2 alpha) and E2 (PGE2) in uterine flushings were measured. During the oestrous cycle, breed effects were detected only for total protein (P = 0.07), which tended to be higher for Large White gilts. However, for pregnant gilts, total recoverable glucose (P less than 0.05), fructose (P less than 0.05) sodium (P less than 0.05), immunoglobulin A (P less than 0.01), PGF (P less than 0.01), PGE (P less than 0.01), and acyl aminopeptidase (P less than 0.05) were greater in uterine flushings from Meishan gilts. Only uteroferrin was higher (P = 0.06) in uterine flushings from Large White gilts. Concentrations of prolactin were higher (P less than 0.05) in plasma from cyclic or pregnant Meishan gilts, but concentrations of total oestrogens and progesterone were not affected by pregnancy status or breed. These results suggest that Meishan conceptuses, individually or collectively, are more stimulatory to endometrial secretion and/or transport of the components of histotroph into the uterine lumen, or that the endometrium of Meishan gilts is more sensitive to conceptus signals responsible for the accumulation of histotroph in the uterine lumen.

The relationship between serum albumin concentration and body protein loss in pregnant sheep

1978 ◽  
Vol 91 (1) ◽  
pp. 173-179 ◽  
Author(s):  
A. R. Sykes ◽  
R. Thompson
Keyword(s):  
Body Weight ◽  
Serum Albumin ◽  
Protein Content ◽  
Early Pregnancy ◽  
Albumin Concentration ◽  
Protein Loss ◽  
Maternal Body ◽  
Body Protein ◽  
Pregnant Sheep ◽  
The Relationship

SummaryData are presented from 104 sheep from three separate sources (batches) in which variation in the degree of maternal body protein loss was induced by nutritional means. The change in body protein content during pregnancy was calculated as the difference between body protein content in early pregnancy, predicted from the relationship with body weight in control sheep killed in early pregnancy, and actual content on slaughter at parturition. Serum albumin and globulin concentrations and body weight were measured at intervals during pregnancy and examined for relationships with body protein change.Highly significant linear relationships were found between the change (%) in albumin concentration during pregnancy or albumin concentration in late pregnancy and the calculated change (%) in maternal body protein content (P < 0·001 in both cases) though fitting separate intercepts for each batoh of sheep led to improvements in fit.Equations for prediction of loss (%) of body protein from change in body weight or maternal body weight during pregnancy though significant, were also improved by fitting separate intercepts for batches. The relative value of the relationships for predicting body protein loss is discussed.Serum globulin concentration was not affected by protein status of the animal.

Sign in / Sign up

Export Citation Format

Share Document