ABSTRACT
Maternal nutrition during gestation has important effects on gene expression-mediated metabolic programming in offspring. To evaluate the effect of a protein-restricted maternal diet during gestation, pancreatic islets from male progeny of Wistar rats were studied at postnatal days (PND) 36 (juveniles) and 90 (young adults). The expression of key genes involved in ß-cell function and the DNA methylation pattern of the regulatory regions of two such genes, Pdx1 (pancreatic and duodenal homeobox 1) and MafA (musculoaponeurotic fibrosarcoma oncogene family, protein A), were investigated. Gene expression analysis in the pancreatic islets of restricted offspring showed significant differences compared with the control group at PND 36 (P < 0.05). The insulin 1 and 2 (Ins1 and Ins2), Glut2 (glucose transporter 2), Pdx1, MafA, and Atf2 (activating transcription factor 2), genes were upregulated, while glucokinase (Gck) and NeuroD1 (neuronal differentiation 1) were downregulated. Additionally, we studied whether the gene expression differences in Pdx1 and MafA between control and restricted offspring were associated with differential DNA methylation status in their regulatory regions. A decrease in the DNA methylation levels was found in the 5' flanking region between nucleotides -8118 to -7750 of the MafA regulatory region in restricted offspring compared with control pancreatic islets. In conclusion, low protein availability during gestation causes the upregulation of MafA gene expression in pancreatic ß-cells in the male juvenile offspring at least in part through DNA hypomethylation. This process may contribute to developmental dysregulation of ß-cell function and influence the long-term health of the offspring.
ABSTRACT
Resumen El trabajo de parto es la transición de un estado de inactividad y relajación muscular a un estado de excitación, en el cual la capa muscular del útero (miometrio) realiza crecientes contracciones coordinadas para llevar a cabo la expulsión del feto y la placenta. Durante el inicio del trabajo de parto, el miometrio experimenta una serie de cambios fisiológicos, bioquímicos y moleculares, pasando de un estado de quiescencia a un fenotipo contráctil que inducirá el parto. En parte, esto es provocado por la acción de las hormonas progesterona, estradiol y oxitocina. En general, la progesterona mantiene la quiescencia del miometrio durante el embarazo al inhibir la expresión de moléculas proinflamatorias y proteínas asociadas a la contracción, mientras que al término del embarazo, el estradiol induce la expresión de dichas moléculas. Por su parte, la oxitocina induce un aumento en la concentración de calcio intracelular para llevar a cabo las contracciones de los miocitos uterinos. El objetivo del presente trabajo es presentar un resumen acerca de los mecanismos moleculares involucrados en la regulación de la actividad de las células miometriales por medio de las hormonas progesterona, estradiol y oxitocina, así como discutir las perspectivas de esta interesante área de investigación.
Abstract Labor is the transition from a state of inactivity and muscle relaxation to a state of muscle excitation, in which the muscular layer of the uterus (myometrium) performs increasingly coordinated contractions to deliver the fetus and expel the placenta. During the onset of labor, the myometrium undergoes a series of physiological, biochemical, and molecular changes, allowing the tissue to transition from a quiescent state to a contractile phenotype that will support labor. This is partly caused by the action of the hormones progesterone, estradiol, and oxytocin. In general, progesterone maintains the quiescence of the myometrium during pregnancy by decreasing the expression of proinflammatory molecules and contraction-associated proteins. In contrast, at the end of pregnancy, estradiol induces the expression of these molecules. For its part, oxytocin induces an increase in intracellular calcium concentration to carry out the contractions of uterine myocytes. The objective of this review is to present a summary of the molecular mechanisms involved in regulating myometrial cell activity through the hormones progesterone, estradiol and oxytocin, as well as to discuss the perspectives of this exciting area of research.
