Impact of Pre-Gestational BMI and Gestational Weight Gain on Fetal Development Outcomes in Adolescent Pregnant Women.

Background. Gestational weight gain (GWG) constitutes an essential aspect of the gestational process. Due to factors such as pregestational body mass index (BMI), nutritional intake, level of physical activity, and psychological aspects, the recommended GWG may not be achieved, leading to adverse neonatal outcomes. Adolescents, due to their physiological and mental developmental stage, are at a higher risk of inappropriate GWG. Our aim is to highlight the importance of GWG in our population and to determine the correlation with perinatal outcomes. Methods. Pregnant adolescents who attended a tertiary care institution for prenatal care were included; maternal data such as preBMI and GWG were used to determine maternal and neonatal outcomes using the chi-square test and OR determination. Results. A total of 202 adolescent pregnant patients were included, comprising those with inadequate GWG (n = 70), adequate GWG (n = 85), and excessive GWG (n = 47). A statistically significant association was found between low BMI and inadequate GWG. Patients with inadequate GWG demonstrated a correlation with IUGR and low birth weight, while patients with excessive GWG gave birth to macrosomic neonates. Conclusion. We concluded that previous habits play a significant role in determining weight gain throughout pregnancy. GWG has a direct impact on neonatal growth and development.

In Vitro Culturing of Human Term Placental Explants.

The study of the human placenta has always been appealing, given the importance of this temporal organ capable of sustaining the beginning of life and development of a new human being within the womb. Culturing placental explants has been an easy and reliable method to study some placental morphological, biochemical, and physiological features for a very long time. Besides low time consumption, requirement of few resources, and wide versatility, the placental explant in vitro culture retains cell-cell interaction in a 3D structure resembling the in vivo setting, which is why it is the option of choice for many researchers in the field. This chapter will describe a simplified method for culturing explants from human term placentas.

In Vitro Culturing of Human Trophoblasts from Term Placenta.

Since the early 1960s, researchers began culturing placental cells to establish an in vitro model to study the biology of human trophoblasts, including their ability to differentiate into syncytiotrophoblasts and secrete steroid and peptide hormones that help sustain a viable pregnancy. This task was addressed by testing different serum concentrations, cell culture media, digestive enzymes, growth factors, substrate coating with diverse proteins from the extracellular matrix, and so on. Among the many methodological challenges, the contamination of trophoblasts with other cell types, such as immune and stromal cells, was a matter of concern. However, introducing the Percoll gradient to isolate cytotrophoblasts was an excellent contribution, and later, the depletion of contaminating cells by using magnetic bead-conjugated antibodies also helped increase the purity of cytotrophoblasts. Herein, with some modifications, we describe a rapid and easy method for cytotrophoblast isolation from the term human placenta based on the previously reported method by Harvey Kliman et al. (Endocrinology 118:1567-1582, 1986). This method yields about 40-90 million cells from a single placenta, with a purity of around 85-90%.

Evaluation of Leukocyte Chemotaxis Induced by Human Fetal Membranes in an In Vitro Model.

Leukocyte infiltration into the maternal-fetal interface is a consequence of the robust inflammation in the gestational tissues during term labor and preterm labor with or without infection. During pregnancy, the fetal membranes act as a physical barrier that isolates the fetus into the amniotic cavity, keeping it in an optimal environment for its development. In addition, the fetal membranes possess immunological competencies such as the secretion of cytokines and chemokines in response to different stimuli. Clinical and experimental evidence indicates that these tissues are involved in the extensive chemotaxis of immune cells in normal or pathological conditions.Few studies have evaluated the chemotactic capacities of the fetal membranes considering that this tissue is composed of two adjacent tissues, the amnion and the chorion, which have different characteristics. Although these tissues function as a unit, their response is complex since there is an interaction between them, where each tissue contributes differently. The protocol described here allows us to evaluate the in vitro chemotactic capacities of fetal membranes in response to various applied stimuli, considering the contribution of each of their components (amnion and choriodecidua) using a Boyden chamber assay and phenotyping the chemo-attracted leukocytes by flow cytometry.

Culture of Human Fetal Membranes in a Two Independent Compartment Model: An Ex Vivo Approach.

During pregnancy, the fetal membranes composed of the amnion and chorodecidua constitute a selective barrier separating two distinct environments, maternal and fetal. These tissues have the function of delimiting the amniotic cavity. Their histological complexity gives them physical, mechanical, and immunological properties to protect the fetus. Although the study of the amnion, chorion, and decidua separately provides knowledge about the functions of the fetal membranes, the protocol we describe in this chapter has the advantage of maintaining the biological and functional complexity of these tissues. In addition, this experimental model allows the researcher to recreate various pathological scenarios because this model allows for differential stimulation of the amnion or choriodecidua.

Immunomodulatory role of decidual prolactin on the human fetal membranes and placenta.

The close interaction between fetal and maternal cells during pregnancy requires multiple immune-endocrine mechanisms to provide the fetus with a tolerogenic environment and protection against any infectious challenge. The fetal membranes and placenta create a hyperprolactinemic milieu in which prolactin (PRL) synthesized by the maternal decidua is transported through the amnion-chorion and accumulated into the amniotic cavity, where the fetus is bedded in high concentrations during pregnancy. PRL is a pleiotropic immune-neuroendocrine hormone with multiple immunomodulatory functions mainly related to reproduction. However, the biological role of PRL at the maternal-fetal interface has yet to be fully elucidated. In this review, we have summarized the current information on the multiple effects of PRL, focusing on its immunological effects and biological significance for the immune privilege of the maternal-fetal interface.

High Glucose Promotes Inflammation and Weakens Placental Defenses against E. coli and S. agalactiae Infection: Protective Role of Insulin and Metformin.

Placentas from gestational diabetes mellitus (GDM) patients undergo significant metabolic and immunologic adaptations due to hyperglycemia, which results in an exacerbated synthesis of proinflammatory cytokines and an increased risk for infections. Insulin or metformin are clinically indicated for the treatment of GDM; however, there is limited information about the immunomodulatory activity of these drugs in the human placenta, especially in the context of maternal infections. Our objective was to study the role of insulin and metformin in the placental inflammatory response and innate defense against common etiopathological agents of pregnancy bacterial infections, such as E. coli and S. agalactiae, in a hyperglycemic environment. Term placental explants were cultivated with glucose (10 and 50 mM), insulin (50-500 nM) or metformin (125-500 µM) for 48 h, and then they were challenged with live bacteria (1 × 105 CFU/mL). We evaluated the inflammatory cytokine secretion, beta defensins production, bacterial count and bacterial tissue invasiveness after 4-8 h of infection. Our results showed that a GDM-associated hyperglycemic environment induced an inflammatory response and a decreased beta defensins synthesis unable to restrain bacterial infection. Notably, both insulin and metformin exerted anti-inflammatory effects under hyperglycemic infectious and non-infectious scenarios. Moreover, both drugs fortified placental barrier defenses, resulting in reduced E. coli counts, as well as decreased S. agalactiae and E. coli invasiveness of placental villous trees. Remarkably, the double challenge of high glucose and infection provoked a pathogen-specific attenuated placental inflammatory response in the hyperglycemic condition, mainly denoted by reduced TNF-α and IL-6 secretion after S. agalactiae infection and by IL-1ß after E. coli infection. Altogether, these results suggest that metabolically uncontrolled GDM mothers develop diverse immune placental alterations, which may help to explain their increased vulnerability to bacterial pathogens.

Compartmentalized Innate Immune Response of Human Fetal Membranes against Escherichia coli Choriodecidual Infection.

An infectious process into the uterine cavity represents a major endangered condition that compromises the immune privilege of the maternal-fetal unit and increases the risk for preterm birth (PTB) and premature rupture of membranes (PROM). Fetal membranes are active secretors of antimicrobial peptides (AMP), which limit bacterial growth, such as Escherichia coli. Nevertheless, the antibacterial responses displayed by chorioamniotic membranes against a choriodecidual E. coli infection have been briefly studied. The objective of this research was to characterize the profile of synthesis, activity, and spatial distribution of a broad panel of AMPs produced by fetal membranes in response to E. coli choriodecidual infection. Term human chorioamniotic membranes were mounted in a two independent compartment model in which the choriodecidual region was infected with live E. coli (1 × 105 CFU/mL). Amnion and choriodecidual AMP tissue levels and TNF-α and IL-1ß secretion were measured by the enzyme-linked immunosorbent assay. The passage of bacterium through fetal membranes and their effect on structural continuity was followed for 24 h. Our results showed that E. coli infection caused a progressive mechanical disruption of the chorioamniotic membranes and an activated inflammatory environment. After the challenge, the amnion quickly (2-4 h) induced production of human beta defensins (HBD)-1, HBD-2, and LL-37. Afterwards (8-24 h), the amnion significantly produced HBD-1, HBD-2, HNP-1-3, S100A7, sPLA2, and elafin, whereas the choriodecidua induced LL-37 synthesis. Therefore, we noticed a temporal- and tissue-specific pattern regulation of the synthesis of AMPs by infected fetal membranes. However, fetal membranes were not able to contain the collagen degradation or the bacterial growth and migration despite the battery of produced AMPs, which deeply increases the risk for PTB and PROM. The mixture of recombinant HBDs at low concentrations resulted in increased bactericidal activity compared to each HBD alone in vitro, encouraging further research to study AMP combinations that may offer synergy to control drug-resistant infections in the perinatal period.

Prolactin Protects the Structural Integrity of Human Fetal Membranes by Downregulating Inflammation-induced Secretion of Matrix Metalloproteinases.

Prolactin (PRL) is a pleiotropic hormone with a key role in pregnancy. In fetal membranes, PRL can regulate the secretion of pro-inflammatory factors, which induces the activation of matrix metalloproteinases (MMPs). The increase and activation of MMPs deregulate the turnover of the extracellular matrix in the fetal membranes, altering its structure and function, causing premature rupture of the membranes and preterm labor. In this work, we evaluate the effect of PRL upon the secretion of MMP-1, MMP-2, MMP-9, MMP-13, and the tissue inhibitors of metalloproteinases (TIMPs) in human fetal membranes after lipopolysaccharide (LPS) challenge. Nine fetal membranes from healthy non-laboring cesarean deliveries at term were cultured in a 2-independent chamber system and pre-treated with 250, 500, 1000 or 4000 ng/ml of PRL for 24 h, then choriodecidual region was stimulated with 500 ng/ml of LPS plus fresh PRL for 24 h. The MMPs and TIMPs secretion were quantified by ELISA, additionally MMP-2 and MMP-9 gelatinolytic activity was measured by zymography. LPS induced the MMP-9 and MMP-1 secretion, but no MMP-2 or MMP-13 in comparison with basal levels. PRL co-treatment decreased the MMP-2, MMP-9 and MMP-1 secretion induced by LPS. The active forms were present in the tissue extract, showing a response consistent with the secretion profile. TIMP-1 and TIMP-2 secretion was decreased after LPS treatment and the PRL co-treatment reverts this effect. The present results support that PRL may favor the balance between these factors involved in the structural maintenance of fetal membranes in an inflammatory event.

Cord Serum Calcitriol Inversely Correlates with Maternal Blood Pressure in Urinary Tract Infection-Affected Pregnancies: Sex-Dependent Immune Implications.

Urinary tract infections (UTI) during pregnancy are frequently associated with hypertensive disorders, increasing the risk of perinatal morbidity. Calcitriol, vitamin D3's most active metabolite, has been involved in blood pressure regulation and prevention of UTIs, partially through modulating vasoactive peptides and antimicrobial peptides, like cathelicidin. However, nothing is known regarding the interplay between placental calcitriol, cathelicidin, and maternal blood pressure in UTI-complicated pregnancies. Here, we analyzed the correlation between these parameters in pregnant women with UTI and with normal pregnancy (NP). Umbilical venous serum calcitriol and its precursor calcidiol were significantly elevated in UTI. Regardless of newborn's sex, we found strong negative correlations between calcitriol and maternal systolic and diastolic blood pressure in the UTI cohort (p < 0.002). In NP, this relationship was observed only in female-carrying mothers. UTI-female placentas showed higher expression of cathelicidin and CYP27B1, the calcitriol activating-enzyme, compared to male and NP samples. Accordingly, cord-serum calcitriol from UTI-female neonates negatively correlated with maternal bacteriuria. Cathelicidin gene expression positively correlated with gestational age in UTI and with newborn anthropometric parameters. Our results suggest that vitamin D deficiency might predispose to maternal cardiovascular risk and perinatal infections especially in male-carrying pregnancies, probably due to lower placental CYP27B1 and cathelicidin expression.

Changes in PPAR-γ Expression Are Associated with microRNA Profiles during Fetal Programming due to Maternal Overweight and Obesity.

BACKGROUND: There has been a global increase in the prevalence of obesity in pregnant women in recent years. Animal studies have shown that intrauterine environment associated with maternal obesity leads to epigenetic changes. However, the effects of epigenetic changes occurring before birth in response to maternal conditions have not been clearly characterized in humans. OBJECTIVE: The aim of the study was to analyze peroxisome proliferator-activated receptor (PPAR)-γ expression in cell cultures from newborns from mothers with overweight and obesity, in response to in vitro metabolic challenges and their relationship with microRNA profile and cytokine expression. Methods/Study design: The profile of circulating microRNAs from 72 mother-child pairs (including healthy infants born to normal weight [n = 35], overweight [n = 25], and obese [n = 12] mothers) was determined through real-time PCR, and the PPAR-γ expression in peripheral blood mononuclear cell cultures from offspring was analyzed after in vitro challenges. RESULTS: miR-146a, miR-155, and miR-378a were upregulated in overweight mothers, while miR-378a was upregulated in obese mothers compared to normal weight mothers. In children from overweight mothers, miR-155 and miR-221 were downregulated and miR-146a was upregulated, while offspring of mothers with obesity showed downregulation of miR-155, miR-221, and miR-1301. These microRNAs have direct or indirect relation with PPAR-γ expression. In vitro exposure to high triglyceride and exposure to miR-378a induced a higher expression of PPAR-γ in cells from offspring of mothers with overweight and obesity. In contrast, cells from offspring of mothers with obesity cultured with high glucose concentrations showed PPAR-γ downregulation. IL-1ß, IL-6, and TNF-α expression in cells of offspring of overweight and obese mothers differed from that of offspring of normal weight mothers. Limitation of our study is the small sample size. CONCLUSION: The blood microRNA profile, and in vitro PPAR-γ and inflammatory cytokine expression in cells of newborn infants are associated with maternal obesity indicating that epigenetic marks may be established during intrauterine development. Key Message: Neonatal microRNA profile is associated with maternal weight. Neonatal microRNA profile is independent of maternal microRNA profile. PPAR-γ expression in newborn cell cultures is affected by maternal weight.

Immunoendocrine Dysregulation during Gestational Diabetes Mellitus: The Central Role of the Placenta.

Gestational Diabetes Mellitus (GDM) is a transitory metabolic condition caused by dysregulation triggered by intolerance to carbohydrates, dysfunction of beta-pancreatic and endothelial cells, and insulin resistance during pregnancy. However, this disease includes not only changes related to metabolic distress but also placental immunoendocrine adaptations, resulting in harmful effects to the mother and fetus. In this review, we focus on the placenta as an immuno-endocrine organ that can recognize and respond to the hyperglycemic environment. It synthesizes diverse chemicals that play a role in inflammation, innate defense, endocrine response, oxidative stress, and angiogenesis, all associated with different perinatal outcomes.

Effect of Experimental Gestational Diabetes Mellitus on Mechanical Sensitivity, Capsaicin-Induced Pain Behaviors and Hind Paw Glabrous Skin Innervation of Male and Female Mouse Offspring.

PURPOSE: Gestational diabetes mellitus (GDM) induces cardiovascular and metabolic disturbances in offspring. However, the effects of GDM in pain processing in offspring and whether male and female offspring are equally affected is not well known. Thus, we determined: i) whether GDM in mice affects offspring hindpaw mechanical sensitivity, capsaicin-induced spontaneous pain-like behaviors, and epidermal nerve fiber density (ENFD); and ii) whether there is sexual dimorphism in these parameters in offspring from GDM dams. METHODS: GDM was induced in pregnant ICR mice via i.p. streptozotocin (STZ). Then, glucose levels from dams and offspring were determined. Male and female offspring 2-3 months of age were evaluated for: a) baseline mechanical sensitivity of the hind paw by using von Frey filaments; b) number of flinches and time spent guarding induced by intraplantar capsaicin (0.1%); and c) density of PGP-9.5 and CGRP axons in the epidermis from the hind paw glabrous skin. RESULTS: Prepartum levels of glucose in STZ-treated dams were significantly increased compared to vehicle-treated dams; however, GDM or vehicle offspring displayed normal and similar blood glucose levels. Male and female GDM offspring showed significantly greater mechanical sensitivity and capsaicin-induced pain behaviors compared to vehicle offspring. Male GDM offspring displayed a slightly more intense nociceptive phenotype in the capsaicin test. PGP-9.5 and CGRP ENFD in hind paw glabrous skin were greater in male and female GDM offspring versus their controls. Sexual dimorphism was generally not observed in GDM offspring in most of the studied parameters. CONCLUSION: These results suggest GDM induced greater pain-like behaviors in adult offspring regardless of sex along with an increased ENFD of PGP-9.5 and CGRP in the hind paw glabrous skin. We show that GDM peripheral neuropathy differs from diabetic peripheral neuropathy acquired in adulthood and set the foundation to further study this in human babies exposed to GDM.

Central role of the placenta during viral infection: Immuno-competences and miRNA defensive responses.

Pregnancy is a unique immunological condition in which an "immune-diplomatic" dialogue between trophoblasts and maternal immune cells is established to protect the fetus from rejection, to create a privileged environment in the uterus and to simultaneously be alert to any infectious challenge. The maternal-placental-fetal interface (MPFI) performs an essential role in this immunological defense. In this review, we will address the MPFI as an active immuno-mechanical barrier that protects against viral infections. We will describe the main viral infections affecting the placenta and trophoblasts and present their structure, mechanisms of immunocompetence and defensive responses to viral infections in pregnancy. In particular, we will analyze infection routes in the placenta and trophoblasts and the maternal-fetal outcomes in both. Finally, we will focus on the cellular targets of the antiviral microRNAs from the C19MC cluster, and their effects at both the intra- and extracellular level.

Placentas associated with female neonates from pregnancies complicated by urinary tract infections have higher cAMP content and cytokines expression than males.

PROBLEM: The cAMP pathway is involved in important biological processes including immune regulation and hormone signaling. At the feto-maternal unit, cAMP participates in placental function/physiology and the establishment of immunoendocrine networks. Low cAMP in male fetuses cord blood has been linked to poorer perinatal outcomes; however, cAMP placental content and its relationship with immune factors and fetal sex in an infectious condition have not been investigated. METHOD OF STUDY: Sex-dependent changes in cAMP content and its association with cytokines and antimicrobial peptides expression were studied in human placentas collected from normal pregnancies and with urinary tract infections (UTI). Radioimmunoassay was used to quantify cAMP in placental tissue, while immune markers expression was studied by qPCR. Additionally, cAMP effect on antimicrobial peptides expression was studied in cultured trophoblasts challenged with lipopolysaccharide, to mimic an infection. RESULTS: In UTI, placentas from female neonates had higher cAMP tissue content and increased expression of TNFA, IL1B, and IL10 than those from males, where IFNG was more elevated. While cAMP negatively correlated with maternal bacteriuria and IFNG, it positively correlated with the antimicrobial peptide S100A9 expression in a sex-specific fashion. In cultured trophoblasts, cAMP significantly stimulated ß-defensin-1 while reduced the lipopolysaccharide-dependent stimulatory effect on ß-defensin-2, ß-defensins-3, and S100A9. CONCLUSION: Our results showed higher cAMP content and defense cytokines expression in placentas associated with female neonates from pregnancies complicated by UTI. The associations between cAMP and bacteriuria/immune markers, together with cAMP's ability to differentially regulate placental antimicrobial peptides expression, suggest a dual modulatory role for cAMP in placental immunity.

Prolactin modifies the in vitro LPS-induced chemotactic capabilities in human fetal membranes at the term of gestation.

PROBLEM: Immune responses of fetal membranes involve the production of chemoattractant mediators causing infiltration of maternal and fetal leukocytes, intrauterine inflammation and potentially the disruption of maternal-fetal tolerance. Prolactin (PRL) has deep immunoregulatory effects in the fetal-maternal interface. We aimed to test the in vitro PRL effect upon chemotactic capacities of human fetal membranes. METHOD OF STUDY: Fetal membranes and umbilical cord blood were collected from healthy non-laboring caesarean deliveries at term. Fetal membranes were cultured in Transwell® frames to mimic the barrier function between choriodecidual and amniotic sides. Tissues were treated with PRL, Lipopolysaccharide (LPS), or both simultaneously. Then, RANTES, MCP-1, MIP-1α, IP-10, and PECAM-1 were quantified in a conditioned medium by choriodecidual or amniotic sides. The chemotaxis of subsets of migrating mononuclear cells from umbilical cord blood was evaluated in a Boyden Chamber in response to the conditioned medium by both sides. RESULTS: Lipopolysaccharide stimulates the production of RANTES, MCP-1, MIP-1α, and PECAM-1 in choriodecidua, while MIP-1α and PECAM-1 only increase in amnion. PRL decrease RANTES, MCP-1, and MIP-1 only in choriodecidua, but PECAM-1 was decreased mainly in amnion. The leukocyte migration was regulated significantly in response to the conditioned medium by the amnion, increase in the conditioned medium after LPS treatment, contrary with, the leukocyte migration decreased in a significant manner in response to conditioned medium after PRL and LPS-PRL co-treatment. Finally, T cells were the most responsive subset of cells. CONCLUSIONS: Prolactin modified in a tissue-specific manner the chemotactic factor and the leukocyte migration differentially in fetal membranes.

Neonatal Sepsis Diagnosis Decision-Making Based on Artificial Neural Networks.

Neonatal sepsis remains difficult to diagnose due to its non-specific signs and symptoms. Traditional scoring systems help to discriminate between septic or not patients, but they do not consider every single patient particularity. Thus, the purpose of this study was to develop an early- and late-onset neonatal sepsis diagnosis model, based on clinical maternal and neonatal data from electronic records, at the time of clinical suspicion. A predictive model was obtained by training and validating an artificial Neural Networks (ANN) algorithm with a balanced dataset consisting of preterm and term non-septic or septic neonates (early- and late-onset), with negative and positive culture results, respectively, using 25 maternal and neonatal features. The outcome of the model was sepsis or not. The performance measures of the model, evaluated with an independent dataset, outperformed physician's diagnosis using the same features based on traditional scoring systems, with a 93.3% sensitivity, an 80.0% specificity, a 94.4% AUROC, and a regression coefficient of 0.974 between actual and simulated results. The model also performed well-relative to the state-of-the-art methods using similar maternal/neonatal variables. The top 10 factors estimating sepsis were maternal age, cervicovaginitis and neonatal: fever, apneas, platelet counts, gender, bradypnea, band cells, catheter use, and birth weight.

Host Defense Peptide RNase 7 Is Down-regulated in the Skin of Diabetic Patients with or without Chronic Ulcers, and its Expression is Altered with Metformin.

BACKGROUND: Diabetic foot ulcers (DFUs) are one of the main complications in patients with type 2 diabetes mellitus (DM2), previous studies have reported that DM2 patients have lower production of host defense peptides (HDP). AIM OF THE STUDY: To investigate the expression of RNase 7, cathelicidin, HBD-2, and psoriasin in biopsies obtained from DM2 patients with or without DFU. METHODS: Biopsies from DFU patients grade 3 according to Wagner's classification, from diabetic patients without ulcer and from healthy donors were obtained. qPCR, immunohistochemistry and cell line cultures were performed. To assess whether L-isoleucine, calcitriol, phenyl butyrate, metformin, glyburide or insulin induced RNase 7, keratinocytes were stimulated, and RNase 7 expression was evaluated. RESULTS: Our data showed that RNase 7 levels were decreased in both diabetic groups when were compared with skin from healthy donors. Since most of the DM2 patients are treated with drugs to reduce glycemia, we investigated whether glyburide, metformin or insulin were able to induce any change regarding RNase 7 production. Results showed that metformin reduces the expression of RNase 7 in in vitro treated keratinocytes, suggesting that the chronic use of metformin should be evaluated in DFU patients, whereas calcitriol, phenyl butyrate and L-isoleucine did not increase the RNase 7 production. CONCLUSIONS: Due RNase 7 has antimicrobial activity, its downregulation can make prone to DM2 patients to develop infections and impaired wound healing.

Innate Immune Cells and Toll-like Receptor-Dependent Responses at the Maternal-Fetal Interface.

During pregnancy, the placenta, the mother and the fetus exploit several mechanisms in order to avoid fetal rejection and to maintain an immunotolerant environment throughout nine months. During this time, immune cells from the fetal and maternal compartments interact to provide an adequate defense in case of an infection and to promote a tolerogenic milieu for the fetus to develop peacefully. Trophoblasts and decidual cells, together with resident natural killer cells, dendritic cells, Hofbauer cells and other macrophages, among other cell types, contribute to the modulation of the uterine environment to sustain a successful pregnancy. In this review, the authors outlined some of the various roles that the innate immune system plays at the maternal-fetal interface. First, the cell populations that are recruited into gestational tissues and their immune mechanisms were examined. In the second part, the Toll-like receptor (TLR)-dependent immune responses at the maternal-fetal interface was summarized, in terms of their specific cytokine/chemokine/antimicrobial peptide expression profiles throughout pregnancy.

Expression of nuclear factor-erythroid 2-related factor 2 in rat brain following the administration of kainic acid and pentylenetetrazole.

Epilepsy is a neurological disorder of the central nervous system characterized by hypersynchronized neuronal activity and has been associated with oxidative stress. Oxidative stress interferes with the expression of genes as well as transcriptional factors such as nuclear factor-erythroid 2-related factor 2 (Nrf2). We evaluated the expression of Nrf2 in the rat brain in treated with kainic acid (KA) and pentylenetetrazole (PTZ). Nrf2 immunoreactivity was observed in astrocytes of the hippocampal region in rats exposed at KA. Nrf2 expression was increased significantly in rats with KA and PTZ. These results provide evidence that the increased expression of Nrf2 is part of the mechanism against KA and PTZ toxicity.