RESUMEN
Antioxidants have been widely used during in vitro production to decrease the negative effect of reactive oxygen species. It was reported that the complex resveratrol-methyl ß-cyclodextrin (RV-CD) improves resveratrol's stability and bioavailability and increases its antioxidant activity. This study evaluates the effect of RV-CD during in vitro oocyte maturation (IVM) or in vitro embryo culture (IVC) on developmental competence and quantitative changes in gene expression of developmental important genes. In experiment 1, RV-CD was added to IVM media and maturation level, embryo development and oocytes, cumulus cells, and blastocysts gene expression by RT-qPCR were examined. In experiment 2, presumptive zygotes were cultured in SOF supplemented with RV-CD and embryo development and blastocysts gene expression by RT-qPCR were studied. A group without RV-CD (control- ) and a group with cyclodextrin (control+ ) were included. No differences were found in cleavage rate or blastocyst yield between groups. However, the expression of LIPE was higher in blastocysts derived from oocytes treated with resveratrol compared with control groups (p < .05). Blastocysts produced by IVC with resveratrol showed that RV-CD could modify the expression of genes related to lipid metabolism (CYP51A1, PNPLA2 and MTORC1) compared with control groups (p < .05). RV-CD in the IVM and IVC media could reduce accumulated fat by increasing lipolysis and suppressing lipogenesis of blastocysts.
Asunto(s)
Bovinos/embriología , Ciclodextrinas/farmacología , Técnicas de Cultivo de Embriones/veterinaria , Embrión de Mamíferos/efectos de los fármacos , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Estilbenos/farmacología , Animales , Ciclodextrinas/administración & dosificación , Relación Dosis-Respuesta a Droga , Técnicas de Maduración In Vitro de los Oocitos/veterinaria , Metabolismo de los Lípidos/efectos de los fármacos , Oocitos/efectos de los fármacos , Oocitos/fisiología , Resveratrol , Estilbenos/administración & dosificaciónRESUMEN
OBJECTIVES: To clarify potential differences between denosumab (DNS) and bisphosphonates (BIS) in terms of bone density and bone metabolism, in a sample of postmenopausal women. METHODS: A total of 113 postmenopausal women aged 53-66 years were treated with either DNS or BIS for 12 months. Bone densitometry and laboratory tests were compared between baseline and follow-up. RESULTS: Femoral neck BMD increased in both treatment-arms (FN-BMD, DNS: 0.69±0.07 g/cm2 to 0.75±0.09 g/cm2; BIS: 0.69±0.06 g/cm2 to 0.71±0.07 g/cm2; p≤0.001 in both cases). Lumbar spine BMD (LS-BMD) increased significantly only in the DNS-group (0.83±0.14 g/cm2 to 0.89±0.14 g/cm2, p=0.0001). Only women under treatment with DNS had a significant increase in serum parathyroid hormone (PTH: 44.87±17.54 pg/mL to 53.27±15.77 pg/mL, p=0.04), independently of baseline vitamin D levels. DNS-administration resulted in higher increase from baseline in FN-BMD compared to BIS (DNS vs BIS: 8.7%±8.5 vs 3.8%±7.3, p=0.004). Finally, baseline 25OH vitamin D levels did not determine the extent of PTH-increase following administration of DNS- or BIS-treatment. CONCLUSIONS: Both treatments increased BMD, however, the effect of DNS on FN-BMD was superior compared to that of BIS. DNS-treatment increased serum PTH. Baseline 25OH vitamin D levels did not predict the extent of PTH increase at follow-up.
Asunto(s)
Densidad Ósea/efectos de los fármacos , Calcio/metabolismo , Denosumab/farmacología , Difosfonatos/farmacología , Posmenopausia/efectos de los fármacos , Posmenopausia/metabolismo , Anciano , Densidad Ósea/fisiología , Conservadores de la Densidad Ósea/farmacología , Conservadores de la Densidad Ósea/uso terapéutico , Denosumab/uso terapéutico , Difosfonatos/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Osteoporosis Posmenopáusica/metabolismo , Osteoporosis Posmenopáusica/prevención & control , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Offspring telomere length (TL) has been correlated with paternal TL, but the mechanism for this parent of origin-specific inheritance remains unclear. The objective of this study has been to determine the role of spermatozoa TL in embryonic telomere lengthening by using two mouse models showing dimorphism in their spermatozoa TL: Mus musculus vs Mus spretus and old vs young Mus musculus. Mus spretus spermatozoa displayed a shorter TL than Mus musculus. Hybrid offspring exhibited lower TL compared with Mus musculus starting at the two-cell stage, before the onset of telomerase expression. To analyze the role of spermatozoa telomeres in early telomere lengthening, we compared the TL in oocytes, zygotes, two-cell embryos and blastocysts produced by parthenogenesis or by fertilization with Mus musculus or Mus spretus spermatozoa. TL was significantly higher in spermatozoa compared with oocytes, and it increased significantly from the oocyte to the zygote stage in those embryos fertilized with Mus musculus spermatozoa, but not in those fertilized with Mus spretus spermatozoa or produced by parthenogenesis. A further increase was noted from the zygote to the two-cell stage in fertilized Mus musculus embryos, whereas hybrid embryos maintained the oocyte TL. Spermatozoa TL shortened with age in Mus musculus and the offspring from young males showed a significantly higher TL compared with that fathered by old males. These significant differences were already noticeable at the two-cell stage. These results suggest that spermatozoa telomeres act as a guide for telomerase-independent telomere lengthening resulting in differences in TL that persist after birth.
Asunto(s)
Embrión de Mamíferos/ultraestructura , Espermatozoides/ultraestructura , Telómero/ultraestructura , Envejecimiento , Animales , Secuencia de Bases , Blastocisto/ultraestructura , Femenino , Fertilización In Vitro , Masculino , Ratones , Datos de Secuencia Molecular , Oocitos/ultraestructura , Partenogénesis , Telomerasa/metabolismo , Telómero/química , Homeostasis del Telómero , Cigoto/ultraestructuraRESUMEN
Endocannabinoids are known to mediate practically all reproductive events in mammals; however, little is known about their role in oocyte maturation. Through RT-PCR and immunocytochemistry, this study confirms the presence of CB1 and CB2 cannabinoid receptors in bovine oocytes and shows how exposure to the exogenous cannabinoids HU-210 and THC during their in vitro maturation (IVM) activates the phosphorylation of AKT and ERK1/2 proteins associated with the resumption of meiosis. Although supplementation with HU-210 or THC during IVM did not increase blastocyst yields, the expression of interferon tau (IFNτ) and gap junction alpha-1 protein (GJA1) was enhanced at the blastocyst stage. Our data suggest that cannabinoid agonists may be useful IVM supplements as their presence during oocyte maturation upregulates the expression in blastocysts of key genes for embryo quality.
Asunto(s)
Dronabinol/análogos & derivados , Dronabinol/farmacología , Técnicas de Maduración In Vitro de los Oocitos , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Oocitos/citología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Animales , Agonistas de Receptores de Cannabinoides/farmacología , Bovinos , Células Cultivadas , Desarrollo Embrionario/efectos de los fármacos , Antagonistas de Aminoácidos Excitadores/farmacología , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Oocitos/efectos de los fármacos , Oocitos/fisiología , Oogénesis/efectos de los fármacos , Oogénesis/fisiología , Receptor Cannabinoide CB1/agonistas , Receptor Cannabinoide CB1/metabolismo , Receptor Cannabinoide CB2/agonistas , Receptor Cannabinoide CB2/metabolismoRESUMEN
OBJECTIVE: The adaptation of the brain to aging is subject to the impact of psychological and environmental factors and possibly climacteric symptomatology. We aimed to determine the association of climacteric symptomatology with different aspects of episodic memory in a sample of Greek menopausal women. METHODS: This cross-sectional study included 39 postmenopausal women with subjective memory complaints. Memory performance was evaluated using the Hopkins Verbal Learning Test (HVLT) and the revised Brief Visuospatial Memory Test (BVMT), assessing verbal and visuospatial episodic memory, respectively. We evaluated general cognitive status using the Mini-Mental State Examination (MMSE) and the Clock Drawing Test. Menopausal symptoms were assessed using Greene's Climacteric scale. RESULTS: In the multivariate approach, vasomotor symptoms predicted independently HVLT (retained percentage and delayed recall: b-coefficient = -0.568, p = 0.009 and b-coefficient = -0.563, p = 0.012, respectively). Psychological symptoms predicted independently MMSE (b-coefficient = -0.391, p = 0.024); and in combination with free estrogens (logFEI), psychological symptoms predicted BVMT (total and delayed recall: b-coefficient = -0.558, p = 0.001 and b-coefficient = -0.474, p = 0.005) and HVLT discrimination index (b-coefficient = -0.390, p = 0.023). Combined symptomatology predicted independently MMSE (b-coefficient = -0.457, p = 0.006) and HVLT total (b-coefficient = -0.557, p = 0.034); combined symptomatology predicted in combination with logFEI scores of BVMT total (b-coefficient = -0.593, p < 0.001), BVMT delayed recall (b-coefficient = -0.492, p = 0.002). CONCLUSION: The intensity of psychological, vasomotor and combined climacteric symptoms predicted cognitive performance in this sample of postmenopausal women. A differential contribution of vasomotor symptoms to episodic memory is described, with the negative impact being more pronounced in visuospatial rather than verbal episodic memory.
Asunto(s)
Envejecimiento/psicología , Trastornos de la Memoria/fisiopatología , Memoria Episódica , Posmenopausia/fisiología , Posmenopausia/psicología , Adulto , Anciano , Estudios Transversales , Femenino , Grecia , Humanos , Persona de Mediana Edad , Pruebas Neuropsicológicas , Proyectos Piloto , Aprendizaje VerbalRESUMEN
Maternal metabolic disorders linked to lipolysis are major risk factors for reproductive failure. A notable feature of such disorders is increased non-esterified fatty acid (NEFA) concentrations in the blood, which are reflected in the ovarian follicular fluid. Elevated NEFA concentrations impact on the maturing oocyte and even alter subsequent embryo physiology. The aetiological mechanisms have not been fully elucidated. Therefore, in the present study, bovine in vitro maturing cumulus-oocyte complexes were exposed (24 h) to three different maturation treatments containing: (1) physiological (72 µM) NEFA concentrations (=control); (2) elevated (75 µM) stearic acid (SA) concentrations (=HIGH SA); and (3) elevated (425 µM) NEFA concentrations (=HIGH COMBI). Zygotes were fertilised and cultured following standard procedures. Transcriptomic analyses in resulting Day 7.5 blastocysts revealed that the major pathways affected are related to lipid and carbohydrate metabolism in HIGH COMBI embryos and to lipid metabolism and cell death in HIGH SA embryos. Furthermore, lower glutathione content and a reduced number of lipid droplets per cell were observed in HIGH SA-exposed oocytes and resulting morulae, respectively, compared with their HIGH COMBI-exposed counterparts. Vitrified embryos originating from HIGH SA-exposed oocytes tended to exhibit lower survival rates compared with controls. These data suggest possible mechanisms explaining why females across species suffering lipolytic disorders experience difficulties in conceiving.
Asunto(s)
Blastocisto/metabolismo , Ácidos Grasos no Esterificados/farmacología , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Técnicas de Maduración In Vitro de los Oocitos/veterinaria , Oocitos/efectos de los fármacos , Fenotipo , Análisis de Varianza , Animales , Blastocisto/efectos de los fármacos , Bovinos , Cartilla de ADN/genética , Ácidos Grasos no Esterificados/sangre , Femenino , Perfilación de la Expresión Génica/veterinaria , Análisis por Micromatrices , Reacción en Cadena en Tiempo Real de la Polimerasa , Ácidos EsteáricosRESUMEN
OBJECTIVES: We aimed to evaluate the association between circulating androgens and the presence of psychological symptoms in a sample of healthy middle-aged women. METHODS: Psychological and depressive symptoms were evaluated in a total of 207 postmenopausal women, using the Symptom Checklist-90-R (SCL-90R) and the Zung Depression Scale, respectively. We investigated the associations between the SCL-90R and Zung Scale scores, and anthropometric, lifestyle parameters, as well as serum levels of androgens. RESULTS: The free androgen index was positively associated with scores of depression (b-coefficient ± standard error (SE) = 0.2 ± 0.2, p = 0.040), anxiety (b-coefficient ± SE = 0.2 ± 0.2, p = 0.028), anger/aggressiveness (b-coefficient ± SE = 0.3 ± 0.2, p = 0.026), psychotism (b-coefficient ± SE = 0.3 ± 0.1, p = 0.013) as well as with the global index of the SCL-90R scale (b-coefficient ± SE = 0.2 ± 0.1, p = 0.036), while sex hormone binding globulin was negatively associated with depression (b-coefficient ± SE = -0.2 ± 0.0, p = 0.046) and psychotism (b-coefficient ± SE = -0.2 ± 0.0, p = 0.047). These associations were independent of vasomotor symptomatology, smoking and hormone therapy intake and were more pronounced in younger (≤ 5.5 years) compared to older postmenopausal women. Levels of dehydroepiandrosterone sulfate were positively associated with interpersonal sensitivity (b-coefficient ± SE = 0.3 ± 0.3, p = 0.042), psychotism (b-coefficient ± SE = 0.4 ± 0.2, p = 0.007) and the global index (b-coefficient ± SE = 0.3 ± 0.2, p = 0.040) in women < 5.5 years postmenopausal. No significant associations were observed between the Zung or Greene Scale scores and levels of androgens. CONCLUSION: Higher androgenicity was positively associated with symptoms of anxiety and depression in postmenopausal women. These associations were stronger in women closer to the menopausal transition, a finding which may suggest that menopause rather than aging may mediate the association of androgens with mood disorders.
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Andrógenos/sangre , Trastornos del Humor/sangre , Posmenopausia/sangre , Adulto , Anciano , Agresión/fisiología , Ira/fisiología , Ansiedad/sangre , Estudios Transversales , Sulfato de Deshidroepiandrosterona/sangre , Depresión/sangre , Femenino , Humanos , Persona de Mediana Edad , Globulina de Unión a Hormona Sexual/análisisRESUMEN
This study examined the effect of a single administration of human chorionic gonadotrophin (hCG) on Day 1 to 4 after oestrus on corpus luteum (CL) development and circulating progesterone (P4). Oestrus-synchronized heifers (n=43) were administered a single intramuscular injection of saline on Day 1 (control) or 3000IU hCG on Day 1, 2, 3 or 4 after oestrus. Administration of hCG on Day 1 had no effect on CL area, on Day 2 increased CL area from Day 6 to 12 (P<0.05), on Day 3 increased CL area from Day 9 to 11, while on Day 4 increased CL size on Days 9 and 10 (P<0.05). Administration of hCG on Day 4 induced the formation of an accessory CL in 89% of heifers, resulting in a significant increase in total luteal tissue area on the ovaries compared with all other groups. Consistent with the effects on the CL, hCG on Day 1 did not affect P4 concentrations, on Day 2 significantly increased P4 compared with the control from Day 6 to 11 (P<0.05), on Day 3 resulted in a non-significant increase in P4 while hCG on Day 4 increased P4 from Day 8 to 13 compared with the control (P<0.05). In conclusion, administration of hCG as early as Day 2 after oestrus results in increased P4 in circulation from Day 6, which should have beneficial downstream effects in terms of uterine receptivity and conceptus elongation.
Asunto(s)
Gonadotropina Coriónica/farmacología , Cuerpo Lúteo/crecimiento & desarrollo , Luteinización/fisiología , Progesterona/sangre , Animales , Cruzamiento/métodos , Bovinos , Cuerpo Lúteo/diagnóstico por imagen , Cuerpo Lúteo/efectos de los fármacos , Sincronización del Estro , Femenino , Humanos , Luteinización/efectos de los fármacos , Modelos Estadísticos , UltrasonografíaRESUMEN
The aim of the present study was to investigate the effect of short-term progesterone (P4) supplementation during the early metoestrous period on circulating P4 concentrations and conceptus development in cattle. The oestrous cycles of cross-bred beef heifers were synchronised using a 7-day P4-releasing intravaginal device (PRID® Delta; 1.55 g P4) treatment with administration of a prostaglandin F(2α) analogue (Enzaprost; CEVA Sante Animale) the day before PRID® Delta removal. Only those heifers recorded in standing oestrus (Day 0) were used. In Experiment 1, heifers were randomly assigned to one of five groups: (1) control: no treatment; (2) placebo: insertion of a blank device (no P4) from Day 3 to Day 7; (3) insertion of a PRID® Delta from Day 3 to Day 7; (4) insertion of a PRID® Delta from Day 3 to Day 5; or (5) insertion of a PRID® Delta from Day 5 to Day 7. In vitro-produced blastocysts were transferred to each heifer in Groups 2-5 on Day 7 (n=10 blastocysts per heifer) and conceptuses were recovered when heifers were killed on Day 14. Based on the outcome of Experiment 1, in Experiment 2 heifers were artificially inseminated at oestrus and randomly assigned to one of three treatment groups: (1) placebo; (2) PRID from Day 3 to Day 5; or (3) PRID from Day 3 to Day 7. All heifers were killed on Day 16 and recovered conceptuses were incubated in synthetic oviducal fluid medium for 24 h; spent media and uterine flushes were analysed for interferon-τ (IFNT). In both experiments, daily blood samples were taken to determined serum P4 concentrations. Data were analysed using the PROC MIXED procedure of SAS (SAS Institute, Cary, NC, USA). Insertion of a PRID resulted in an increase (P<0.05) in serum P4 that declined following removal. In Experiment 1, P4 supplementation from Day 3 to Day 5 (17.0±1.4 mm) or Day 3 to Day 7 (11.3±2.3 mm) increased conceptus length compared with placebo (2.1±1.8 mm). Serum P4 was significantly lower from Day 9 to Day 14 (P<0.05) and the weight of the Day 14 corpus luteum (CL) was lower in the PRID Day 3-7 group than the placebo or control groups. In Experiment 2, supplementation from Day 3 to Day 5 (94.0±18.8 mm) or Day 3 to Day 7 (143.6±20.6 mm) increased conceptus length on Day 16 compared with placebo (50.3±17.4 mm). Serum P4 was significantly lower in the two supplemented groups following PRID removal compared with placebo (P<0.05) and was associated with a lower CL weight in the Day 3-7 group. Conceptus length was strongly correlated with the IFNT concentration in the uterine flush (r=0.58; P=0.011) and spent culture medium (r=0.68; P<0.002). The findings of the present study highlight the somewhat paradoxical effects of P4 supplementation when given in the early metoestrous period in terms of its positive effect on conceptus development and its potentially negative effects on CL lifespan.
Asunto(s)
Cuerpo Lúteo/efectos de los fármacos , Implantación del Embrión/efectos de los fármacos , Fármacos para la Fertilidad Femenina/administración & dosificación , Fertilidad/efectos de los fármacos , Progesterona/administración & dosificación , Técnicas Reproductivas Asistidas/veterinaria , Administración Intravaginal , Animales , Blastocisto/efectos de los fármacos , Blastocisto/fisiología , Bovinos , Cuerpo Lúteo/fisiología , Esquema de Medicación , Técnicas de Cultivo de Embriones/veterinaria , Transferencia de Embrión/veterinaria , Desarrollo Embrionario/efectos de los fármacos , Ciclo Estral/efectos de los fármacos , Ciclo Estral/fisiología , Femenino , Fármacos para la Fertilidad Femenina/sangre , Fertilización In Vitro/veterinaria , Inseminación Artificial/veterinaria , Embarazo , Progesterona/sangre , Factores de TiempoRESUMEN
OBJECTIVE: Recent evidence suggests that climacteric symptoms may be intensified by specific temperament and personality traits in postmenopausal women. In this study we investigate Cloninger's model of personality in relation to menopausal symptoms. METHODS: One-hundred and seventy peri- and postmenopausal women consecutively recruited from a menopause clinic of an academic hospital completed the Cloninger's Temperament and Character Inventory (TCI-140) which measures four dimensions of temperament: Harm avoidance, Novelty seeking, Reward dependence and Persistence, as well as three dimensions of character: Self-directedness, Cooperativeness, and Self-transcendence. Menopausal somatic, vasomotor and psychological symptoms were also assessed using the Greene Climacteric Scale. RESULTS: In comparison to the norms of the Greek general population, postmenopausal women presented lower scores in Novelty seeking and Reward dependence and higher scores in Persistence, Self-directedness, Cooperativeness and Self-transcendence. Higher harm avoidance (the inclination to avoid potential punishment, be shy and fearful of uncertainty) significantly correlated with anxiety and depressive symptoms while lower Self-directedness (the ability to have the willpower to adapt to or overcome any changes) correlated with depressive symptoms only. By multivariate regression analysis, higher Harm avoidance and lower Self-directedness were independently associated with the presence of depressive symptoms. No significant associations were observed between TCI-140 traits and somatic or vasomotor symptoms. CONCLUSIONS: Our findings indicate that most temperament and character traits according to Cloninger's model in peri- and postmenopausal women varied significantly as compared to the general population. Among several traits, high Harm avoidance and low Self-directedness were most strongly associated with psychological climacteric distress but not with somatic and vasomotor symptoms.
Asunto(s)
Adaptación Psicológica/fisiología , Ansiedad , Depresión , Sofocos , Menopausia , Personalidad , Temperamento/clasificación , Ansiedad/etiología , Ansiedad/fisiopatología , Ansiedad/psicología , Carácter , Estudios Transversales , Depresión/etiología , Depresión/fisiopatología , Depresión/psicología , Femenino , Grecia , Sofocos/etiología , Sofocos/fisiopatología , Sofocos/psicología , Humanos , Menopausia/fisiología , Menopausia/psicología , Persona de Mediana Edad , Personalidad/clasificación , Personalidad/fisiología , Inventario de Personalidad , Estadística como Asunto , Sistema Vasomotor/fisiopatologíaRESUMEN
BACKGROUND: Extracellular vesicles (EVs) present in oviductal (OF) and uterine fluid (UF) have been shown to enhance bovine embryo quality during in vitro culture by reducing lipid contents and modulating lipid metabolism-related genes (LMGs), while also influencing cell proliferation, suggesting their involvement on the regulation of different biological pathways. The regulation of signaling pathways related to cell differentiation, proliferation, and metabolism is crucial for early embryo development and can determine the success or failure of the pregnancy. Bioactive molecules within EVs in maternal reproductive fluids, such as microRNAs (miRNAs), may contribute to this regulatory process as they modulate gene expression through post-transcriptional mechanisms. RESULTS: From the 20 differentially expressed miRNAs, 19 up-regulated in UF-EVs (bta-miR-134, bta-miR-151-3p, bta-miR-155, bta-miR-188, bta-miR-181b, bta-miR-181d, bta-miR-224, bta-miR-23b-3p, bta-miR-24-3p, bta-miR-27a-3p, bta-miR-29a, bta-miR-324, bta-miR-326, bta-miR-345-3p, bta-miR-410, bta-miR-652, bta-miR-677, bta-miR-873 and bta-miR-708) and one (bta-miR-148b) in OF-EVs. These miRNAs were predicted to modulate several pathways such as Wnt, Hippo, MAPK, and lipid metabolism and degradation. Differences in miRNAs found in OF-EVs from the early luteal phase and UF-EVs from mid-luteal phase may reflect different environments to meet the changing needs of the embryo. Additionally, miRNAs may be involved, particularly in the uterus, in the regulation of embryo lipid metabolism, immune system, and implantation. This study evaluated miRNA cargo in OF-EVs from the early luteal phase and UF-EVs from the mid-luteal phase, coinciding with embryo transit within oviduct and uterus in vivo, and its possible influence on LMGs and signaling pathways crucial for early embryo development. A total of 333 miRNAs were detected, with 11 exclusive to OF, 59 to UF, and 263 were common between both groups. CONCLUSIONS: Our study suggests that miRNAs within OF- and UF-EVs could modulate bovine embryo development and quality, providing insights into the intricate maternal-embryonic communication that might be involved in modulating lipid metabolism, immune response, and implantation during early pregnancy.
RESUMEN
Elevated plasma nonesterified fatty acid (NEFA) concentrations are associated with negative energy balance and metabolic disorders such as obesity and type II diabetes. Such increased plasma NEFA concentrations induce changes in the microenvironment of the ovarian follicle, which can compromise oocyte competence. Exposing oocytes to elevated NEFA concentrations during maturation affects the gene expression and phenotype of the subsequent embryo, notably prompting a disrupted oxidative metabolism. We hypothesized that these changes in the embryo are a consequence of modified energy metabolism in the oocyte. To investigate this, bovine cumulus oocyte complexes were matured under elevated NEFA conditions, and energy metabolism-related gene expression, mitochondrial function, and ultrastructure evaluated. It was found that expression of genes related to REDOX maintenance was modified in NEFA-exposed oocytes, cumulus cells, and resultant blastocysts. Moreover, the expression of genes related to fatty acid synthesis in embryos that developed from NEFA-exposed oocytes was upregulated. From a functional perspective, inhibition of fatty acid ß-oxidation in maturing oocytes exposed to elevated NEFA concentrations restored developmental competence. There were no clear differences in mitochondrial morphology or oxygen consumption between treatments, although there was a trend for a higher mitochondrial membrane potential in zygotes derived from NEFA-exposed oocytes. These data show that the degree of mitochondrial fatty acid ß-oxidation has a decisive impact on the development of NEFA-exposed oocytes. Furthermore, the gene expression data suggest that the resulting embryos adapt through altered metabolic strategies, which might explain the aberrant energy metabolism previously observed in these embryos originating from NEFA-exposed maturing oocytes.
Asunto(s)
Bovinos/embriología , Ácidos Grasos no Esterificados/farmacología , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Técnicas de Maduración In Vitro de los Oocitos , Oocitos/citología , Oocitos/efectos de los fármacos , Animales , Células Cultivadas , Células del Cúmulo/citología , Células del Cúmulo/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Embrión de Mamíferos/citología , Embrión de Mamíferos/efectos de los fármacos , Femenino , Regulación del Desarrollo de la Expresión Génica/fisiología , Técnicas In Vitro , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/ultraestructura , Modelos Animales , Ácido Oléico/farmacología , Consumo de Oxígeno/efectos de los fármacos , Consumo de Oxígeno/fisiología , Ácido Palmítico/farmacología , Ácidos Esteáricos/farmacologíaRESUMEN
OBJECTIVE: To assess the interaction of the MTHFR C677T polymorphism with changes in lipid and glucose metabolism effected by oral hormone replacement therapy (HRT) in postmenopausal women. METHODS: In this open-label, prospective, interventional study, parameters of lipid and glucose metabolism, as well as homocysteine, were assessed in 97 postmenopausal women at baseline and 1 year after the initiation of HRT. Participants were stratified into three subgroups, according to the MTHFR C677T polymorphism (wild-type: CC genotype; heterozygous: CT genotype; homozygous for the mutant variable: TT genotype). RESULTS: The TT genotype was associated with an elevation of total and low density lipoprotein (LDL) cholesterol, while CT and CC genotypes were associated with a reduction of total cholesterol and LDL cholesterol after 1 year of HRT (p = 0.032 for total cholesterol and p = 0.002 for LDL cholesterol). Women with the TT genotype had higher glucose levels in contrast to women with the CC genotype who had lower glucose levels after 1 year of HRT (p = 0.011). Additionally, CC carriers under HRT had a significant elevation of apolipoprotein A1 levels (p = 0.018), contrarily to CT and TT genotypes. CONCLUSION: While HRT was associated with favorable changes in lipid and metabolic parameters in carriers of the CC genotype, this effect was not evident in carriers of the T allele. The MTHFR C677T polymorphism may modify the effect of HRT on lipid and metabolic parameters in postmenopausal women.
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Terapia de Reemplazo de Estrógeno , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Polimorfismo Genético , Posmenopausia/metabolismo , Adulto , Glucemia/análisis , Índice de Masa Corporal , Colesterol/sangre , LDL-Colesterol/sangre , Femenino , Genotipo , Glucosa/metabolismo , Homocisteína/sangre , Humanos , Metabolismo de los Lípidos , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Triglicéridos/sangreRESUMEN
BACKGROUND: Early treatment of breast cancer patients with loco-regional relapse or contralateral disease has been shown to improve survival. There is no current consensus on the optimal follow-up strategy. This study estimates the risk of isolated contralateral relapse (CR) after breast cancer surgery and its change over time, together with the efficacy of clinical examination, self-examination and mammography in the detection of CR. METHODS: Data from patients treated for early breast cancer at Guy's Hospital between 1990 and 1997 were collected and those with isolated contralateral recurrences were analysed. Life table analysis was performed and CR, CR-free and cumulative CR rates were calculated. Correlations were evaluated using Pearson's correlation coefficient. RESULTS: One thousand one hundred and forty-three women were included in the study and 23 patients had isolated CR. The median probability of CR was a constant 0.24% per year. Only one recurrence was found clinically at follow up, while the majority was detected through mammography and self-palpation. CONCLUSIONS: The risk of CR is low and constant with time. Contralateral mammography is useful and can detect the vast majority of contralateral recurrences. These findings may have practical implications especially on the planning of postmastectomy follow up.
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Neoplasias de la Mama/cirugía , Recurrencia Local de Neoplasia/etiología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/radioterapia , Autoexamen de Mamas , Detección Precoz del Cáncer/métodos , Femenino , Estudios de Seguimiento , Humanos , Tablas de Vida , Mamografía , Mastectomía Segmentaria/métodos , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/diagnóstico , Cuidados PosoperatoriosRESUMEN
Although genetically identical for autosomal Chrs (Chr), male and female preimplantation embryos could display sex-specific transcriptional regulation. To illustrate sex-specific differences at the mRNA level, we compared gene-expression patterns between male and female blastocysts by DNA microarray comparison of nine groups of 60 bovine in vitro-produced blastocysts of each sex. Almost one-third of the transcripts detected showed sexual dimorphism (2,921 transcripts; false-discovery rate, P < 0.05), suggesting that in the absence of hormonal influences, the sex Chrs impose an extensive transcriptional regulation upon autosomal genes. Six genes were analyzed by qPCR in in vivo-derived embryos, which displayed similar sexual dimorphism. Ontology analysis suggested a higher global transcriptional level in females and a more active protein metabolism in males. A gene homolog to an X-linked gene involved in network interactions during spliceosome assembly was found in the Y-Chr. Most of the X-linked-expressed transcripts (88.5%) were up-regulated in females, but most of them (70%) exhibited fold-changes lower than 1.6, suggesting that X-Chr inactivation is partially achieved at the blastocyst stage. Almost half of the transcripts up-regulated in female embryos exhibiting more than 1.6-fold change were present in the X-Chr and eight of them were selected to determine a putative paternal imprinting by gene expression comparison with parthenogenetic embryos. Five (BEX, CAPN6, BEX2, SRPX2, and UBE2A) exhibited a higher expression in females than in parthenotes, suggesting that they are predominantly expressed by the paternal inherited X-Chr and that imprinting may increase the transcriptional skew caused by double X-Chr dosage.
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Blastocisto/metabolismo , Regulación del Desarrollo de la Expresión Génica , Impresión Genómica , Cromosoma X/genética , Cromosoma Y/genética , Animales , Bovinos , Femenino , Perfilación de la Expresión Génica , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Factores Sexuales , Empalmosomas/genética , Transcripción Genética , Inactivación del Cromosoma XRESUMEN
The objective was to examine the effect of lactation on uterine involution in post-partum dairy cows. Holstein primiparous cows were used (n = 19, mean age: 3.9 ± 0.1 years). At calving, cows were randomly assigned to one of two treatment groups, lactating (n = 11) or non-lactating (i.e. dried off at calving, n = 8). Examination of the reproductive tract was carried out by ultrasonography twice weekly until week 7 post-partum. Blood samples were collected twice weekly for the analysis of progesterone to indicate the resumption of cyclicity and metabolites indicative of energy status. Uterine involution was assessed in terms of size of the uterine horns, uterine body diameter and uterine fluid volume as assessed by the amount of non-echogenic material measured by ultrasound and position of the uterus. Vaginal mucous score was taken on day 28 post-partum for the assessment of uterine inflammation. Resumption of cyclicity (serum progesterone > 1 ng/ml) had occurred in both groups on average by day 21 post-partum. Concentrations of non-esterified fatty acids and beta-hydroxybutyrate were higher, whereas concentrations of glucose, insulin and IGF-1 were lower (p < 0.05) in lactating compared to non-lactating cows. Lactating cows had a smaller mean uterine body diameter (p < 0.05) than non-lactating cows from days 28 to 42 post-partum (day 28: 20.2 ± 1.3 vs 24.9 ± 1.5 mm, respectively) and had a lower mean uterine fluid volume up to day 49 (p < 0.05). By day 49, there was no difference in uterine diameter (15.2 ± 1.8 vs 15.2 ± 1.6 mm) or uterine fluid volume (0.11 ± 0.38 vs 0.18 ± 0.46) between lactating and non-lactating cows, respectively. Vaginal mucous score revealed no evidence of uterine inflammation in either group. In conclusion, while lactation induced significant alterations in metabolic status, it did not have a major effect on the rate of uterine involution as defined in this study.
Asunto(s)
Bovinos/fisiología , Lactancia/fisiología , Periodo Posparto/fisiología , Útero/fisiología , Animales , Composición Corporal , Peso Corporal , Femenino , EmbarazoRESUMEN
Poly(lactic acid) (PLA) is considered the most promising biobased substitute for fossil-derived polymers due to its compostability, biocompatibility, renewability, and good thermomechanical properties. However, PLA suffers from several shortcomings, such as low heat distortion temperature, thermal resistance, and rate of crystallization, whereas some other specific properties, i.e., flame retardancy, anti-UV, antibacterial or barrier properties, antistatic to conductive electrical characteristics, etc., are required by different end-use sectors. The addition of different nanofillers represents an attractive way to develop and enhance the properties of neat PLA. Numerous nanofillers with different architectures and properties have been investigated, with satisfactory achievements, in the design of PLA nanocomposites. This review paper overviews the current advances in the synthetic routes of PLA nanocomposites, the imparted properties of each nano-additive, as well as the numerous applications of PLA nanocomposites in various industrial fields.
RESUMEN
The aim of this study was to investigate, in unstimulated and superstimulated heifers, the effect of follicle aspiration just before ovulation on corpus luteum (CL) development, circulating progesterone (P(4)) concentrations and the ability of the uterus to support embryo development. Following follicle aspiration or ovulation timed from GNRH administration, CL development was assessed by daily ultrasonography, and CL function was assessed in terms of the capacity to produce P(4) and the expression of genes involved in steroidogenesis in luteal tissue. The capacity of the uterine environment to support conceptus development was assessed following transfer and recovery of in vitro-produced embryos. Follicular aspiration just before the expected time of ovulation leads to a significant reduction in CL diameter, CL area and area of luteal tissue. This was associated with a decrease in circulating P(4) in both unstimulated and superstimulated heifers. Follicle aspiration leads to a reduction in conceptus length and area on day 14 in unstimulated heifers only. Follicle aspiration leads to a reduction in the expression of LHCGR in luteal tissue from unstimulated heifers compared with those in which the CL formed after ovulation. Superstimulation significantly reduced the expression of STAR in luteal tissue in both ovulated and follicle-aspirated heifers. In conclusion, in stimulated and unstimulated heifers, aspiration of the preovulatory dominant follicle(s) just before expected ovulation interferes with the subsequent formation and function of the CL, in terms of size and P(4) output and this, in turn, is associated with a reduced capacity of the uterus to support conceptus elongation in unstimulated heifers.