Elizabeth Sanchez

Expression and regulation of chemerin during rat pregnancy

BACKGROUND Chemerin is an adipocytokine that is expressed in different fat deposits and has been shown to play an important role in adaptive and innate immunity due to its activity as a chemoattractant. Chemerin acts as a ligand for the G protein-coupled receptor chemokine-like receptor 1 (CMKLR1). Chemerin has been shown to regulate the development and metabolic function of adipocytes, liver and muscle tissue. OBJECTIVE There is evidence indicating that several adipocytokines play an important role in placenta. This study aimed to investigate the regulation of chemerin in rat and human placentas throughout gestation. DESIGN AND SETTING Chemerin was examined in rat and human placentas using immunohistochemistry. The chemerin expression pattern in the placenta and adipose tissue of female Sprague Dawley rats on days 12, 16, 19 and 21 of gestation (each of these days represents a group of 12 rats) was determined using TaqMan probe-based quantitative real-time PCR. Rat chemerin serum levels were analyzed with ELISA on days 8, 12, 16, 19 and 21 and compared to virgin controls. RESULTS Chemerin expression was detected in the cytoplasm of rat placental trophoblastic cells and third trimester human placental cytotrophoblast and Hofbauers cells. The serum chemerin levels of rats decreased significantly as gestation progressed. Furthermore, placental chemerin mRNA levels rose significantly at day 16 of gestation and decreased significantly towards the end of the gestation period. CONCLUSION Taken together, this data suggests that chemerin may be an important regulator of maternal-fetal metabolism and metabolic homeostasis during pregnancy.

Irisin Levels During Pregnancy and Changes Associated With the Development of Preeclampsia

CONTEXT Irisin is a recently discovered adipomyokine that regulates the differentiation and phenotype of adipose tissue. OBJECTIVE In this study, we investigated the levels of irisin over the three trimesters of gestation in healthy and preeclamptic women and during the follicular and luteal phase of the menstrual cycle in a cohort of healthy eumenoherric women. METHODS Serum irisin was measured by an ELISA in a longitudinal prospective cohort study in 40 healthy pregnant women, 10 mild preeclamptic women, and 20 healthy eumenoherric women during the menstrual cycle to assess irisin levels and correlations with other metabolic parameters. We identified the protein expression of fibronectin type III domain-containing protein 5, the irisin precursor, in human placenta using immunohistochemical approaches in humans. RESULTS Serum irisin levels are higher in the luteal than in the follicular phase in eumenorrheic women. Fibronectin type III domain-containing protein 5, the irisin precursor, is expressed in human placenta, and its serum levels are higher during the entire pregnancy when compared with nonpregnant women. Serum irisin correlates positively with the homeostasis model assessment of estimated insulin resistance in the first trimester of normal pregnancy. Serum irisin levels do not change throughout gestation in preeclamptic women; however, there were lower irisin levels during the third trimester when compared with the normal pregnant group. CONCLUSION Our results suggest that irisin may be involved in reproductive function and in the pregnancy-associated metabolic changes, and this condition may be an irisin-resistant state during gestation.

Serum chemerin levels during normal human pregnancy

During gestation there are important changes in maternal metabolism and an increase in insulin resistance, coinciding with an increase in adiposity. Chemerin is an adipocytokine which is expressed and secreted in various tissues, including placenta, and may play an important role in metabolic regulation during pregnancy. The aim of this study was to determine serum levels of chemerin during gestation and compare them to other indicators of insulin resistance. A cross-sectional study was carried out analyzing serum chemerin levels of 20 pregnant women during three gestational periods, early, middle, and late (between the 10th and 14th, the 23rd and 26th, and the 34th and 37th week) and 20 non-pregnant women were used as a control group. An analysis of chemerin levels during the menstrual cycle was performed in an eumenorrheic group (n=16) in the early follicular (cycle day 4±1) and the midluteal phase (cycle day 22±1), demonstrating that serum chemerin levels did not fluctuate significantly. Serum levels of chemerin were significantly elevated during late gestation when compared to early (P<0.001) and middle (P=0.001) gestation and a negative correlation between serum chemerin and adiponectin levels (r=-0.1643) became more significant when the non-pregnant group was included in the calculations (r=-0.2471). There was no significant association of triglycerides, total cholesterol, LDL, HDL, insulin, and HOMA levels with chemerin. Although chemerin rose significantly and is negatively associated with adiponectin levels, it is not correlated with other markers of insulin sensitivity, suggesting that more study is needed to determine whether chemerin is useful in predicting insulin resistance during gestation.

Brain‐derived neurotrophic factor is expressed in rat and human placenta and its serum levels are similarly regulated throughout pregnancy in both species

Pregnancy is characterized by several metabolic changes that promote fat gain and later onset of insulin resistance. As Brain‐derived neurotrophic factor (BDNF) decreases hyperglycaemia and hyperphagia, we aimed to investigate the potential role of placental and circulating BDNF levels in these pregnancy‐related metabolic changes in rats and humans.

Regulation of NucB2/Nesfatin-1 throughout rat pregnancy

Nesfatin-1 is an anorexigenic neuropeptide derived by post-translational cleavage from the N-terminus region DNA binding/EF-hand/acidic amino acid rich region (NEFA)/nucleobindin2 (NucB2) protein through proteolytic prohormone convertases. This neuropeptide was originally localized in different appetite controlling areas such as the hypothalamic paraventricular nucleus, arcuate nucleus, supraoptic nucleus, lateral hypothalamic area, and nucleus tractus solitarius. The objective of this study was to determine the expression and the changes that occur to mRNA and protein of NucB2 and Nesfatin-1 serum levels during gestation. This study utilized molecular and immunological approaches to investigate the expression and regulation of NucB2/Nesfatin-1 protein throughout gestation in rat fed under ad libitum and food restricted conditions (30% nutrient restriction). NucB2 was immunolocalized in the amnion and decidua of the rat placenta. Nesfatin-1 serum levels were measured by radioimmunoassay on gestational days 12, 16, 19 and 21, showing a significant (p<0.01) decrease in serum levels after day 12 until the end of gestation in rats fed ad libitum. These results were correlated with the analysis of NucB2 mRNA, with a significant (p<0.01) reduction observed in both the mRNA and protein of NucB2 during the gestational days 12, 16 and 21. It was also observed that food restriction decreases Nesfatin-1 serum levels and NucB2 placental expression at day 16 of gestation when compared to pregnant rats fed ad libitum. This study illustrates for the first time through molecular and immunological approaches the NucB2 expression and regulation on rat placenta and that this peptide is regulated throughout pregnancy. Consistent with previous reports, our results provide additional evidence supporting the role of NucB2 protein as an anorexigenic peptide that may contribute to the regulation of feeding behavior and energy homeostasis. NucB2/Nesfatin-1 might play an important metabolic role during pregnancy and fetal development and its energy balance mediating role should be studied in various physiological and pathological conditions throughout gestation.

Longitudinal analysis of maternal serum Follistatin concentration in normal pregnancy and preeclampsia

Follistatin (FST) is a regulator of the biological activity of activin A (Act A), binding and blocking it, which could contribute to the modulation of its pro‐inflammatory activity during pregnancy. We sought to investigate, in this nested case–control study, FST serum levels during normal pregnancy and correlate it with the FST profile in preeclamptic pregnant women, normal pregnant women followed 3 months postpartum and eumenorrheic nonpregnant women throughout the menstrual cycle.

IL-9: Function, Sources, and Detection

IL-9 is a pleiotropic cytokine produced in different amounts by a wide variety of cells including mast cells, NKT cells, Th2, Th17, Treg, ILC2, and Th9 cells. Th9 cells are considered to be the main CD4+ T cells that produce IL-9. IL-9 exerts its effects on multiple types of cells and different tissues. To date, its main role has been found in the immune responses against parasites and pathogenesis of allergic diseases such as asthma and bronchial hyperreactivity. Additionally, it induces the proliferation of hematologic neoplasias, including Hodgkins lymphoma in humans. However, IL-9 also has antitumor properties in solid tumors such as melanoma. The objective of this review is to describe IL-9, its function, sources, and methods of detection.

Maternal serum omentin-1 profile is similar in humans and in the rat animal model

Omentin-1 is an adipocytokine with anti-inflammatory activity that has been associated with different metabolic disorders. The aim of this study is to investigate the serum profiles of omentin-1 throughout human and rat pregnancy. Serum omentin-1 levels were determined by ELISA in a prospective cohort study of healthy pregnant women (n=40) during the three trimesters of pregnancy and in twenty healthy non-pregnant women during the follicular and luteal phase of the menstrual cycle. In addition, serum omentin-1 levels were measured in rats during different periods of pregnancy (gestational days 8, 12, 16, 19, and 21) and in an age-matched control (virgin) group of rats (n=12rats/group). Finally, immunohistochemistry was used to demonstrate the presence of omentin-1 protein in human and rat placenta. Omentin-1 immunoreactivity was detected in cytotrophoblasts, syncytiotrophoblasts, sparse Hofbauer cells, and endothelial cells of the stem villi of human placenta. Additionally, it was detected in the labyrinthine trophoblast and yolk sac layer of the rat placenta. Human and rat serum omentin-1 levels were significantly lower in the late gestational period when compared with the non-pregnant women and virgin rats (p<0.05). Serum omentin-1 changes were not significant throughout the gestation in both species (p>0.05). Human serum omentin-1 levels have an inverse relationship with triglyceride levels during pregnancy. Our findings have not determined the exact role of omentin-1 during pregnancy, concerning the metabolic control of triglycerides and other energy sources. Whether omentin-1 decrease implies a regulatory function is still not clear. Further studies are needed to address this issue and determine the role of omentin-1 in metabolic adaptations during normal human and rat pregnancy.

Maternal Serum Meteorin Levels and the Risk of Preeclampsia.

Background Meteorin (METRN) is a recently described neutrophic factor with angiogenic properties. This is a nested case-control study in a longitudinal cohort study that describes the serum profile of METRN during different periods of gestation in healthy and preeclamptic pregnant women. Moreover, we explore the possible application of METRN as a biomarker. Methods and Findings Serum METRN was measured by ELISA in a longitudinal prospective cohort study in 37 healthy pregnant women, 16 mild preeclamptic women, and 20 healthy non-pregnant women during the menstrual cycle with the aim of assessing serum METRN levels and its correlations with other metabolic parameters. Immunostaining for METRN protein was performed in placenta. A multivariate logistic regression model was proposed and a classifier model was formulated for predicting preeclampsia in early and middle pregnancy. The performance in classification was evaluated using measures such as sensitivity, specificity, and the receiver operating characteristic (ROC) curve. In healthy pregnant women, serum METRN levels were significantly elevated in early pregnancy compared to middle and late pregnancy. METRN levels are significantly lower only in early pregnancy in preeclamptic women when compared to healthy pregnant women. Decision trees that did not include METRN levels in the first trimester had a reduced sensitivity of 56% in the detection of preeclamptic women, compared to a sensitivity of 69% when METRN was included. Conclusions The joint measurements of circulating METRN levels in the first trimester and systolic blood pressure and weight in the second trimester significantly increase the probabilities of predicting preeclampsia.