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1.
Domest Anim Endocrinol ; 77: 106648, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34314944

RESUMEN

Skeletal muscle plays an integral role in the ability of a horse to perform at high levels. Shifts in skeletal muscle development in response to maternal plane of nutrition may have substantial and lasting impacts on athletic performance and whole-body metabolism. Therefore, sixteen Quarter Horse mares were used in a completely randomized design and maintained at a body condition score (BCS) 6 until start of third trimester. On d 235 of gestation, mares were randomly assigned to receive one of two dietary treatments with a diet formulated to meet requirements during late gestation (CON; n = 8), and an overfed diet (HIGH; n = 8) where mares received an additional 40% above CON. Five h after parturition, foals were euthanized, and gluteus medius, triceps brachii, and semitendinosus were harvested for analyses. Gene expression was determined by qPCR and western immunoblotting was used to quantify total and phosphorylated forms of proteins involved in skeletal muscle metabolism with tubulin as the loading control. All data were analyzed using PROC MIXED of SAS. Foals from HIGH mares exhibited larger skeletal muscle fibers by area (P <0.05), and a shift in muscle fiber development towards type I slow twitch muscle fibers (P <0.05). Relative expression of glucose transporter 4 (GLUT4) was lower in HIGH foals compared to CON in gluteus medius (P = 0.05). Insulin receptor isoform B (INSR-B) and insulin-like growth factor 1 receptor (IGF1R) were greater in triceps brachii of HIGH foals compared to CON (P ≤ 0.03). Insulin receptor isoform A (INSR-A), however, tended to be lower in triceps brachii of HIGH compared to CON (P = 0.10). Ratios of phosphorylated to total extracellular signal-regulated protein kinase 1/2 (ERK1/2) and c-June N-terminal kinase (JNK) were higher in HIGH foals compared to CON (P ≤0.04) in gluteus medius. There were no differences observed for phosphorylated to total protein ratios in semitendinosus and triceps brachii muscles; however, total ERK1/2 tended to be elevated (P <0.10) in semitendinosus from CON foals compared to HIGH. There was no difference in phosphorylated or total protein kinase B (AKT) (P >0.14). These data indicate hypertrophy of skeletal muscle fibers and a shift towards type I slow twitch fibers in HIGH foals. Furthermore, this study identifies muscle specific changes in gene expression and downstream insulin receptor signaling, which may contribute to future metabolic abnormalities in response to maternal overnutrition.


Asunto(s)
Enfermedades de los Caballos , Resistencia a la Insulina , Hipernutrición , Fenómenos Fisiológicos Nutricionales de los Animales/fisiología , Animales , Femenino , Caballos , Insulina/metabolismo , Desarrollo de Músculos , Músculo Esquelético/metabolismo , Hipernutrición/veterinaria , Embarazo
2.
Domest Anim Endocrinol ; 77: 106632, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34062290

RESUMEN

Thyroid hormones regulate a multitude of metabolic and cellular processes involved in placental and fetal growth, while maternal nutrient restriction (NR) has the potential to influence these processes. Those fetuses most impacted by NR, as categorized by weight, are termed small for gestational age (SGA), but the role of thyroid hormones in these pregnancies is not fully understood. Therefore, the aims of the present study were to determine effects of NR during pregnancy on maternal and fetal thyroid hormone concentrations, as well as temporal and cell-specific expression of mRNAs and proteins for placental thyroid hormone transporters, thyroid hormone receptors, and deiodinases in ewes having either SGA or normal weight fetuses. Ewes with singleton pregnancies were fed either a 100% NRC (n = 8) or 50% NRC (NR; n = 28) diet from Days 35 to 135 of pregnancy with a single placentome surgically collected on Day 70. Fetal weight at necropsy on Day 135 was used to designate the fetuses as NR NonSGA (n = 7; heaviest NR fetuses) or NR SGA (n = 7; lightest NR fetuses). Thyroid hormone levels were lower in NR SGA compared to NR NonSGA ewes, while all NR fetuses had lower concentrations of thyroxine at Day 135. Expression of mRNAs for thyroid hormone transporters SLC16A2, SLC16A10, SLCO1C1, and SLCO4A1 were altered by day, but not nutrient restriction. Expression of THRA mRNA and protein was dysregulated in NR SGA fetuses with protein localized to syncytial and stromal cells in placentomes in all groups. The ratio of deiodinases DIO2 and DIO3 was greater for NR SGA placentae at Day 70, while DIO3 protein was less abundant in placentae from NR SGA than 100% NRC ewes. These results identify mid-gestational modifications in thyroid hormone-associated proteins in placentomes of ewes having SGA fetuses, as well as a potential for placentomes from NonSGA pregnancies to adapt to, and overcome, nutritional restrictions during pregnancy.


Asunto(s)
Fenómenos Fisiológicos Nutricionales de los Animales , Placenta , Fenómenos Fisiológicos Nutricionales de los Animales/fisiología , Animales , Femenino , Feto , Edad Gestacional , Nutrientes/metabolismo , Placenta/metabolismo , Embarazo , Ovinos , Hormonas Tiroideas
3.
Anim Reprod Sci ; 227: 106720, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33636430

RESUMEN

Results from previous studies indicate that maternal overnutrition during late gestation predisposes foals to metabolic disease, however, specific mechanisms resulting in disease remain unknown. Quarter Horse mares (n = 16), were randomly assigned to dietary treatments, beginning on gestational day 235, and consisted of a control group (CON- diet meeting nutrient requirement; n = 8) or an overfed diet (HIGH; n = 8) where mares received an additional 40 % above CON. On gestational days 285 and 315, an intravenous glucose tolerance test (FSIGTT) was conducted. Following parturition, foals were separated from the mare, prohibited from nursing, and an FSIGTT was conducted at 2 h postpartum. Foals were immediately euthanized and tissues preserved for analyses. There was no effect of treatment on foal BW (P = 0.50), pancreas weight (P = 0.60), or FSIGTT area under the curve for glucose (P = 0.80) and insulin (P = 0.70). Colocalization of α-amylase to isolate pancreatic islets of Langerhans indicated increased islet number and size in foals from HIGH mares (P < 0.01). Immunofluoresent analysis of insulin, glucagon, and somatostatin indicate no difference in intensity of staining (P> 0.10). Foals exposed to overnutrition during peak fetal growth had altered pancreatic islet development that may lead to adult-onset metabolic disease.


Asunto(s)
Alimentación Animal/análisis , Enfermedades de los Caballos/etiología , Resistencia a la Insulina , Hipernutrición/veterinaria , Páncreas/patología , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Animales Recién Nacidos , Peso Corporal , Dieta/veterinaria , Femenino , Caballos , Insulina/metabolismo , Tamaño de los Órganos , Embarazo
4.
Domest Anim Endocrinol ; 74: 106580, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33160154

RESUMEN

Maternal nutrient restriction during pregnancy alters fetal programming, which modifies the growth and health of the offspring in postnatal life. In cattle, nutrient restriction during pregnancy can be a result of environmental or economic factors, but little is known about how it alters the physiology of the fetus and affects future reproductive or growth efficiency. This study used female monozygotic twins, produced through in vitro fertilization and embryo splitting, to determine the effect of moderate maternal nutrient restriction on fetal development. Recipient Angus cross heifers pregnant with one twin were fed a diet meeting 100% National Research Council (NRC) total energy requirements (n = 4; control), whereas recipient heifers pregnant with the second twin were fed at 70% of NRC total energy requirements (n = 4; restricted) from gestational day (GD) 158 to GD 265 in Calan gate feeders. Recipient heifers were killed at GD 265. Change in maternal metabolic body weight was greater from zero in restricted heifers than controls (P < 0.05); restricted heifers lost weight during the nutrient restriction period. There was no difference in last rib back fat or rib eye area between groups (P > 0.10). There was no difference in fetal weight, uterine weight, or total placentome weight between groups (P > 0.10). The pancreas weight was reduced in restricted fetuses compared with control fetuses (P < 0.01), but there were no other differences in fetal organ weights (P > 0.10). Plasma insulin concentrations were reduced in restricted fetuses compared with controls (P < 0.01), but there was no effect of maternal diet on plasma glucose or glucagon concentrations in the fetus (P > 0.10). Histological analyses of the fetal pancreas revealed no differences in endocrine cell number or localization. Results indicate that a modest late gestation nutritional restriction impairs development of the fetal pancreas in the cow. Additional research will be needed to determine if these developmental changes lead to altered glucose and insulin homeostasis in the adult.


Asunto(s)
Alimentación Animal/análisis , Bovinos/embriología , Dieta/veterinaria , Insulina/metabolismo , Páncreas/embriología , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Técnicas de Cultivo de Embriones , Transferencia de Embrión , Femenino , Desarrollo Fetal , Privación de Alimentos , Páncreas/metabolismo , Embarazo , Fenómenos Fisiologicos de la Nutrición Prenatal , Gemelización Monocigótica
5.
Domest Anim Endocrinol ; 74: 106556, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33120168

RESUMEN

Maternal nutrient restriction (NR) causes small for gestational age (SGA) offspring, which are at higher risk for accelerated postnatal growth and developing insulin resistance in adulthood. Skeletal muscle is essential for whole-body glucose metabolism, as 80% of insulin-mediated glucose uptake occurs in this tissue. Maternal NR can alter fetal skeletal muscle mass, expression of glucose transporters, insulin signaling, and myofiber type composition. It also leads to accumulation of intramuscular triglycerides (IMTG), which correlates to insulin resistance. Using a 50% NR treatment from gestational day (GD) 35 to GD 135 in sheep, we routinely observe a spectral phenotype of fetal weights within the NR group. Thus, we classified those fetuses into NR(Non-SGA; n = 11) and NR(SGA; n = 11). The control group (n = 12) received 100% of nutrient requirements throughout pregnancy. At GD 135, fetal plasma and gastrocnemius and soleus muscles were collected. In fetal plasma, total insulin was lower in NR(SGA) fetuses compared NR(Non-SGA) and control fetuses (P < 0.01), whereas total IGF-1 was lower in NR(SGA) fetuses compared with control fetuses (P < 0.05). Within gastrocnemius, protein expression of insulin receptor (INSRB; P < 0.05) and the glucose transporters, solute carrier family 2 member 1 and solute carrier family 2 member 4, was higher (P < 0.05) in NR(SGA) fetuses compared with NR(Non-SGA) fetuses; IGF-1 receptor protein was increased (P < 0.01) in NR(SGA) fetuses compared with control fetuses, and a lower (P < 0.01) proportion of type I myofibers (insulin sensitive and oxidative) was observed in SGA fetuses. For gastrocnemius muscle, the expression of lipoprotein lipase (LPL) messenger RNA (mRNA) was upregulated (P < 0.05) in both NR(SGA) and NR(Non-SGA) fetuses compared with control fetuses, whereas carnitine palmitoyltransferase 1B (CPT1B) mRNA was higher (P < 0.05) in NR(Non-SGA) fetuses compared with control fetuses, but there were no differences (P > 0.05) for protein levels of LPL or CPT1B. Within soleus, there were no differences (P > 0.05) for any characteristic except for the proportion of type I myofibers, which was lower (P < 0.05) in NR(SGA) fetuses compared with control fetuses. Accumulation of IMTG did not differ (P > 0.05) in gastrocnemius or soleus muscles. Collectively, the results indicate molecular differences between SGA and Non-SGA fetuses for most characteristics, suggesting that maternal NR induces a spectral phenotype for the metabolic programming of those fetuses.


Asunto(s)
Dieta/veterinaria , Feto/efectos de los fármacos , Transportador de Glucosa de Tipo 1/metabolismo , Transportador de Glucosa de Tipo 4/metabolismo , Insulina/metabolismo , Ovinos/embriología , Alimentación Animal , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Glucemia , Femenino , Peso Fetal , Regulación del Desarrollo de la Expresión Génica , Edad Gestacional , Transportador de Glucosa de Tipo 1/genética , Transportador de Glucosa de Tipo 4/genética , Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/genética , Factor I del Crecimiento Similar a la Insulina/metabolismo , Embarazo , Transducción de Señal/efectos de los fármacos
6.
Domest Anim Endocrinol ; 72: 106443, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32222553

RESUMEN

Maternal nutrient restriction causes small for gestational age (SGA) offspring, which exhibit a higher risk for metabolic syndrome in adulthood. Fetal skeletal muscle is particularly sensitive to maternal nutrient restriction, which impairs muscle mass and metabolism. Using a 50% nutrient restriction treatment from gestational day (GD) 35 to GD 135 in sheep, we routinely observe a spectral phenotype of fetal weights within the nutrient-restricted (NR) group. Thus, our objective was to evaluate the effect of maternal NR on muscle mass, myofiber hypertrophy, myonuclear dotation, and molecular markers for protein synthesis and degradation, while accounting for the observed fetal weight variation. Within the NR group, we classified upper-quartile fetuses into NR(Non-SGA) (n = 11) and lower-quartile fetuses into NR(SGA) (n = 11). A control group (n = 12) received 100% of nutrient requirements throughout pregnancy. At GD 135, fetal plasma and organs were collected, and gastrocnemius and soleus muscles were sampled for investigation. Results showed decreased (P < 0.05) absolute tissue/organ weights, including soleus and gastrocnemius muscles, in NR(SGA) fetuses compared to NR(Non-SGA) and control. Myofiber cross-sectional area was smaller in NR(SGA) vs control for gastrocnemius (P = 0.0092) and soleus (P = 0.0097) muscles. Within the gastrocnemius muscle, the number of myonuclei per myofiber was reduced (P = 0.0442) in NR(SGA) compared to control. Cortisol may induce protein degradation. However, there were no differences in fetal cortisol among groups. Nevertheless, for gastrocnemius muscle, cortisol receptor (NR3C1; P = 0.0124), and FOXO1 (P = 0.0131) were upregulated in NR(SGA) compared to control while NR(Non-SGA) did not differ from the other 2 groups. KLF15 was upregulated (P = 0.0002) in both NR(SGA) and NR(Non-SGA); while FBXO32, TRIM63, BCAT2 or MSTN did not differ. For soleus muscle, KLF15 mRNA was upregulated (P = 0.0145) in NR(SGA) compared to control, and expression of MSTN was increased (P = 0.0259) in NR(SGA) and NR(Non-SGA) compared to control. At the protein level, none of the mentioned molecules nor total ubiquitin-labeled proteins differed among groups (P > 0.05). Indicators of protein synthesis (total and phosphorylated MTOR, EI4EBP1, and RPS6KB1) did not differ among groups in either muscle (P > 0.05). Collectively, results highlight that maternal NR unequally affects muscle mass in NR(SGA) and NR(Non-SGA) fetuses, and alterations in myofiber cross-sectional area and myonuclei number partially explain those differences.


Asunto(s)
Alimentación Animal , Desarrollo Fetal , Privación de Alimentos , Músculo Esquelético , Ovinos , Animales , Femenino , Embarazo , Alimentación Animal/análisis , Fenómenos Fisiológicos Nutricionales de los Animales , Dieta/veterinaria , Edad Gestacional , Músculo Esquelético/crecimiento & desarrollo , Fenómenos Fisiologicos de la Nutrición Prenatal , Ovinos/crecimiento & desarrollo
7.
J Anim Sci ; 93(5): 2094-9, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-26020305

RESUMEN

Brown adipose tissue (BAT) plays a critical role in regulating body temperature in newborn lambs. Availability of a stable BAT cell line would be invaluable for biochemical studies to elucidate cellular and molecular mechanisms responsible for nutritional regulation of fetal BAT growth and development. Ovine brown adipocyte precursor cells (BAPC) were isolated from fetal lambs at d 90 of gestation and cultured to establish a stable cell line. These cells were characterized by adipogenic differentiation and expression of a hallmark gene, (). The BAPC doubled every 24 h. After a 9-d induction with a serum-free Dulbecco's modified Eagle Ham/F12 medium, BAPC differentiated into brown adipocytes with large lipid droplets. The differentiation medium induced expression of mRNA and protein in BAPC. Furthermore, after BAPC were passaged 30 times, they maintained similar cell morphology, the potential for adipogenic differentiation, and the ability to express . Taken together, we have established a stable ovine BAPC cell line for studying nutritional regulation of BAT growth and development in the fetus.


Asunto(s)
Adipocitos Marrones/citología , Tejido Adiposo Pardo/fisiología , Oveja Doméstica/fisiología , Animales , Diferenciación Celular/fisiología , Línea Celular , ARN Mensajero/metabolismo , Ovinos , Oveja Doméstica/genética
8.
J Anim Sci ; 88(13 Suppl): E195-204, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19854987

RESUMEN

Pigs suffer up to 50% embryonic and fetal loss during gestation and exhibit the most severe naturally occurring intrauterine growth retardation among livestock species. Placental insufficiency is a major factor contributing to suboptimal reproductive performance and reduced birth weights of pigs. Enhancement of placental growth and function through nutritional management offers an effective solution to improving embryonic and fetal survival and growth. We discovered an unusual abundance of the arginine family of AA in porcine allantoic fluid (a reservoir of nutrients) during early gestation, when placental growth is most rapid. Arginine is metabolized to ornithine, proline, and nitric oxide, and these compounds possess a plethora of physiological functions. Nitric oxide is a vasodilator and angiogenic factor, whereas both ornithine and proline are substrates for placental synthesis of polyamines, which are key regulators of protein synthesis and angiogenesis. Additionally, arginine, leucine, glutamine, and proline activate the mammalian target of rapamycin cell-signaling pathway to enhance protein synthesis and cell proliferation in placentae. To translate basic research on AA biochemistry and nutrition into application, dietary supplementation with 0.83% l-arginine to gilts on d 14 to 28 or d 30 to 114 of gestation increased the number and litter birth weight of live-born piglets. In addition, supplementing the gestation diet with 0.4% l-arginine plus 0.6% l-glutamine enhanced the efficiency of nutrient utilization, reduced variation in piglet birth weight, and increased litter birth weight. By regulating syntheses of nitric oxide, polyamines, and proteins, functional AA stimulate placental growth and the transfer of nutrients from mother to embryo or fetus to promote conceptus survival, growth, and development.


Asunto(s)
Aminoácidos/fisiología , Fenómenos Fisiológicos Nutricionales de los Animales/fisiología , Resultado del Embarazo/veterinaria , Porcinos/fisiología , Tejido Adiposo/embriología , Tejido Adiposo/crecimiento & desarrollo , Aminoácidos/metabolismo , Animales , Dieta/veterinaria , Femenino , Desarrollo Fetal/efectos de los fármacos , Desarrollo Fetal/fisiología , Retardo del Crecimiento Fetal/veterinaria , Tamaño de la Camada/efectos de los fármacos , Tamaño de la Camada/fisiología , Músculo Esquelético/embriología , Músculo Esquelético/crecimiento & desarrollo , Placenta/fisiología , Embarazo , Porcinos/embriología
9.
Biol Reprod ; 79(3): 518-24, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18495679

RESUMEN

Interferon-tau (IFNT) is secreted by the conceptus trophoblast and signals pregnancy recognition in ruminants. IFNT regulates expression of genes in the endometrium, peripheral blood leukocytes (PBLs), and corpus luteum (CL). Microarray analysis identified that expression of (chemosensory) receptor transporter protein 4 (RTP4) increased in PBLs during early pregnancy in cows. In the present study, we cloned and characterized RTP4 transcription during early pregnancy in ewes. Endometrium, PBLs, and CL were collected on Days 11, 13, and 15 of the cycle and on Days 11, 13, 15, 17, and 19 of pregnancy. Northern blot analysis revealed an expected 1.6-kb mRNA and an unexpected 2.6-kb mRNA. In endometria, RTP4 mRNA levels in cyclic ewes remained low, whereas RTP4 mRNA increased from Day 11 to Day 17 in pregnant ewes. Levels of RTP4 mRNA also increased from Day 15 to Day 19 in CL and PBL samples from pregnant ewes only. The RTP4 mRNA was located in the glandular epithelium, stratum compactum, and caruncular stroma. Ovine glandular epithelial cells were treated with IFNT to determine if IFNT alone could induce RTP4. IFNT increased RTP4 more than 70-fold at 1.5 h after treatment, with maximal induction of nearly 300-fold above values observed in nontreated controls at 6 h after treatment. These results indicate that RTP4 mRNA levels are induced in the ovine endometrium, PBLs, and CL by IFNT during early pregnancy and in cell culture in response to IFNT. If RTP4 expression affects G protein-coupled receptor function, it may be important for establishment of pregnancy in domestic ruminants.


Asunto(s)
Endometrio/metabolismo , Ciclo Estral/metabolismo , Leucocitos/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Ovario/metabolismo , Embarazo/metabolismo , Ovinos/genética , Secuencia de Aminoácidos , Animales , Cuerpo Lúteo/efectos de los fármacos , Cuerpo Lúteo/metabolismo , Endometrio/efectos de los fármacos , Ciclo Estral/sangre , Ciclo Estral/efectos de los fármacos , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Interferón Tipo I/farmacología , Proteínas de Transporte de Membrana/sangre , Proteínas de Transporte de Membrana/genética , Datos de Secuencia Molecular , Ovario/efectos de los fármacos , Embarazo/genética , Proteínas Gestacionales/farmacología , Análisis de Secuencia de ADN , Homología de Secuencia de Aminoácido , Ovinos/metabolismo , Distribución Tisular
10.
Amino Acids ; 35(4): 691-702, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18330497

RESUMEN

Although there are published studies of proline biochemistry and nutrition in cultured cells and postnatal animals, little is known about proline metabolism and function in the conceptus (embryo/fetus, associated placental membranes, and fetal fluids). Because of the invasive nature of biochemical research on placental and fetal growth, animal models are often used to test hypotheses of biological importance. Recent evidence from studies with pigs and sheep shows that proline is a major substrate for polyamine synthesis via proline oxidase, ornithine aminotransferase, and ornithine decarboxylase in placentae. Both porcine and ovine placentae have a high capacity for proline catabolism and polyamine production. In addition, allantoic and amniotic fluids contain enzymes to convert proline into ornithine, which is delivered through the circulation to placental tissues. There is exquisite metabolic coordination among integrated pathways that support highest rates of polyamine synthesis and concentrations in placentae during early gestation when placental growth is most rapid. Interestingly, reduced placental and fetal growth are associated with reductions in placental proline transport, proline oxidase activity, and concentrations of polyamines in gestating dams with either naturally occurring or malnutrition-induced growth retardation. Conversely, increasing proline availability in maternal plasma through nutritional or pharmacological modulation in pigs and sheep enhances concentrations of proline and polyamines in placentae and fetal fluids, as well as fetal growth. These novel findings suggest an important role for proline in conceptus metabolism, growth and development, as well as a potential treatment for intrauterine growth restriction, which is a significant problem in both human medicine and animal agriculture.


Asunto(s)
Embrión de Mamíferos/metabolismo , Desarrollo Fetal , Prolina/metabolismo , Aminoácidos/metabolismo , Animales , Femenino , Humanos , Modelos Biológicos , Placenta/metabolismo , Poliaminas/metabolismo , Embarazo , Preñez , Ovinos , Porcinos
11.
Endocrinology ; 149(1): 219-31, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17901226

RESUMEN

In ruminants, endometrial prostaglandin F(2alpha) (PGF(2alpha)) is the luteolytic hormone. Cellular transport of PGF(2alpha) in the uterine endometrium is critical for regulation of the estrous cycle. Molecular mechanisms responsible for control of PGF(2alpha) transport in endometrium during luteolysis are largely unknown. In the present study, we characterized the prostaglandin transporter (PGT) in ovine endometrium. Ovine PGT cDNA consists of 1935 nucleotides that encode 644 amino acids. In ovine endometria, PGT is highly expressed during the period of luteolysis, between d 14 and 16 of the estrous cycle, in luminal and glandular epithelia. Pharmacological and genomic inhibition of PGT indicates that it is responsible for influx and efflux of PGF(2alpha) in ovine endometrial epithelial cells. Inhibition of PGT during the period of luteolysis prevents the release of oxytocin-induced PGF(2alpha) pulses, and maintains functional corpus luteum and its secretion of progesterone. In ovine endometrial epithelial cells, protein kinase A and protein kinase C pathways are involved in regulating the influx of PGF(2alpha), whereas epidermal growth factor receptor pathways are implicated in regulation of influx and efflux of PGF(2alpha.) The ERK1/2 pathway is associated with efflux of PGF(2alpha), whereas Jun-amino-terminal kinase/stress-activated protein kinase pathways are involved in both efflux and influx of PGF(2alpha.) Phosphatidylinositol 3-kinase pathways are not involved in either influx or efflux of PGF(2alpha) in ovine endometrial epithelial cells. These are the first results to demonstrate a functional role for PGT in regulation of PGF(2alpha) efflux and influx in ovine endometrial cells that influence luteolytic mechanisms in ruminants.


Asunto(s)
Dinoprost/metabolismo , Endometrio/metabolismo , Transportadores de Anión Orgánico/genética , Ovinos/genética , Transducción de Señal/fisiología , Ácido 4,4'-Diisotiocianostilbeno-2,2'-Disulfónico/farmacología , Secuencia de Aminoácidos , Animales , Clonación Molecular , Células Epiteliales/metabolismo , Ciclo Estral/genética , Ciclo Estral/metabolismo , Femenino , Regulación de la Expresión Génica , Luteólisis/efectos de los fármacos , Luteólisis/genética , Modelos Biológicos , Datos de Secuencia Molecular , Especificidad de Órganos , Transportadores de Anión Orgánico/antagonistas & inhibidores , Transportadores de Anión Orgánico/metabolismo , Transportadores de Anión Orgánico/fisiología , Transducción de Señal/genética
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