RESUMO
Endometritis is a common disease in animals, leading to disruption of reproductive processes and economic losses. Noradrenergic control of prostaglandin (PG)I2 formation by inflamed endometrium is unknown. We determined the involvement of α1-, α2- and ß-adrenoreceptors (ARs) in noradrenaline-influenced PGI synthase (PGIS) protein abundance and PGI2 release from porcine (1) endometrial explants with Escherichia coli (E. coli)-induced inflammation in vivo, and (2) E. coli lipopolysaccharide (LPS)-treated endometrial epithelial cells. Experiment 1. E. coli suspension (E. coli group) or saline (CON group) was injected into the uterine horns. In both groups, noradrenaline increased endometrial PGIS abundance and PGI2 release versus the control values, and it was higher in the E. coli group than in the CON group. In the CON group, a noradrenaline stimulating effect on both parameters takes place through α1D-, α2C- and ß2-ARs. In the E. coli group, noradrenaline increased PGIS abundance and PGI2 release via α1A-, α2(B,C)- and ß(1,2)-ARs, and PGI2 release also by α2A-ARs. Experiment 2. LPS and noradrenaline augmented the examined parameters in endometrial epithelial cells versus the control value. In LPS-treated cells, ß(1,2)-ARs mediate in noradrenaline excitatory action on PGIS protein abundance and PGI2 release. ß3-ARs also contribute to PGI2 release. Under inflammatory conditions, noradrenaline via ARs increases PGI2 synthesis and release from the porcine endometrium, including epithelial cells. Our findings suggest that noradrenaline may indirectly affect processes regulated by PGI2 in the inflamed uterus.
Assuntos
Endométrio , Epoprostenol , Norepinefrina , Animais , Feminino , Norepinefrina/metabolismo , Endométrio/metabolismo , Endométrio/patologia , Suínos , Epoprostenol/metabolismo , Receptores Adrenérgicos/metabolismo , Lipopolissacarídeos , Inflamação/metabolismo , Inflamação/patologia , Escherichia coli , Endometrite/metabolismo , Endometrite/patologia , Células Epiteliais/metabolismo , Células Epiteliais/efeitos dos fármacos , Oxirredutases Intramoleculares/metabolismo , Sistema Enzimático do Citocromo P-450RESUMO
Glyphosate is the active ingredient of glyphosate-based herbicides and the most commonly used pesticide in the world. The goal of the present study was to verify whether low doses of glyphosate (equivalent to the environmental exposure) evoke changes in galanin expression in intramural neurons in the small intestine in pigs and to quantitatively determine changes in the level of galanin receptor encoding mRNA (GALR1, GALR2, GALR3) in the small intestine wall. The experiment was conducted on 15 sexually immature gilts divided into three study groups: control (C)-animals receiving empty gelatin capsules; experimental 1 (G1)-animals receiving a low dose of glyphosate (0.05 mg/kg b.w./day); experimental 2 (G2)-animals receiving a higher dose of glyphosate (0.5 mg/kg b.w./day) orally in gelatine capsules for 28 days. Glyphosate ingestion led to an increase in the number of GAL-like immunoreactive intramural neurons in the porcine small intestine. The results of RT-PCR showed a significant increase in the expression of mRNA, which encodes the GAL-receptors in the ileum, a decreased expression in the duodenum and no significant changes in the jejunum. Additionally, intoxication with glyphosate increased the expression of SOD2-encoding mRNA in the duodenum and decreased it in the jejunum and ileum, but it did not affect SOD1 expression. The results suggest that it may be a consequence of the cytotoxic and/or neurotoxic properties of glyphosate and/or its ability to induce oxidative stress.
Assuntos
Galanina , Glifosato , Animais , Feminino , Galanina/metabolismo , Glifosato/metabolismo , Glifosato/toxicidade , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/metabolismo , Receptor Tipo 2 de Galanina/efeitos dos fármacos , Receptor Tipo 2 de Galanina/genética , Receptor Tipo 2 de Galanina/metabolismo , RNA Mensageiro/metabolismo , Sus scrofa/genética , Suínos , Receptor Tipo 1 de Galanina/efeitos dos fármacos , Receptor Tipo 1 de Galanina/genética , Receptor Tipo 1 de Galanina/metabolismo , Receptor Tipo 3 de Galanina/efeitos dos fármacos , Receptor Tipo 3 de Galanina/genética , Receptor Tipo 3 de Galanina/metabolismo , Herbicidas/toxicidadeRESUMO
Endometritis and metritis are common reproductive diseases in domestic animals, causing a reduction in reproductive performance and economic losses. A previous study revealed the alterations in the transcriptome of the inflamed porcine endometrium. Data on molecular signatures in the myometrium under inflammatory conditions are limited. The current study analyzed the transcriptomic profile of porcine myometrium after intrauterine Escherichia coli (E.coli) administration. On day 3 of the estrous cycle (Day 0 of the study), 50 ml of either saline (group CON, n = 7) or E. coli suspension (109 colony-forming units/ml, group E. coli, n = 5) were injected into each uterine horn. After eight days, the gilts were euthanized, and the uteri were removed for further analysis. In the myometrium of the CON group versus the E. coli group, microarray analysis revealed 167 differentially expressed genes (DEGs, 78 up- and 89 down-regulated). After intrauterine E. coli administration, among the DEGs of the inflammatory response set, the highest expressed were mRNA for CXCL6, S100A8, S100A12, SLC11A1, S100A9, CCL15, CCR1, CD163, THBS1 and SOCS3, while the most suppressed was mRNA expression for FFAR4, KL, SLC7A2 and MOAB. Furthermore, a comparison of the present results on myometrial transcriptome with the authors' earlier published data on the endometrial transcriptome shows the partial differences in mRNA expression between both layers after intrauterine E.coli injections. This study, for the first time, presents changes in the transcriptome of porcine myometrium after intrauterine E.coli administration, which may be important for myometrial homeostasis and functions and, as a result, for the uterine inflammation course. Data provide a valuable resource for further studies on genes and pathways regulating uterine inflammation and functions.