Lead exposure at the feto-maternal interface: A cause for concern for fetal membrane trophoblasts.

The integrity of fetal membranes enables biological functions that protect the fetus and maintain the pregnancy. Any compromise in fetal membrane function can predispose a pregnant woman to prelabor rupture of the membranes (pPROM) and subsequently to preterm birth (PTB). Epidemiologic data suggest that lead exposure during pregnancy is one of several risk factors associated with PTB and pPROM.

Galectin-1 Elicits a Tissue-Specific Anti-Inflammatory and Anti-Degradative Effect Upon LPS-Induced Response in an Ex Vivo Model of Human Fetal Membranes Modeling an Intraamniotic Inflammation.

Problem: Intrauterine infection is one of the most jeopardizing conditions associated with adverse outcomes, including preterm birth; however, multiple tolerance mechanisms operate at the maternal-fetal interface to avoid the rejection of the fetus. Among the factors that maintain the uterus as an immunoprivileged site, Galectin-1 (Gal-1), an immunomodulatory glycan-binding protein secreted by the maternal-fetal unit, is pivotal in promoting immune cell homeostasis. This work aimed to evaluate the role of Gal-1 during a lipopolysaccharide (LPS)-induced-inflammatory milieu.

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.

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.

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.

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.

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.

High Glucose Promotes Inflammation and Weakens Placental Defenses against and 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 and , in a hyperglycemic environment.

Compartmentalized Innate Immune Response of Human Fetal Membranes against 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 . Nevertheless, the antibacterial responses displayed by chorioamniotic membranes against a choriodecidual infection have been briefly studied.

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.

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.

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.

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).

Selective immuno-modulatory effect of prolactin upon pro-inflammatory response in human fetal membranes.

During pregnancy, prolactin (PRL) is a neuro-immuno-cytokine that contributes actively to the crosstalk between the immune and endocrine systems and, thus, to the creation of an immune-privileged milieu. This work aims to analyze the capacity of PRL to modulate the synthesis and secretion of pro-inflammatory markers associated with labor. Studies were conducted using human fetal membranes at term mounted in a model of two independent chambers.

Metallothionein expression in the rat brain following KA and PTZ treatment.

Epilepsy is a neurological disorder that has been associated with oxidative stress therefore epilepsy models have been develop such as kainic acid and pentylenetetrazol are usually used to understanding of the molecular mechanisms of this disease. We examined the metallothionein expression in rat brains of treated with kainic acid and pentylenetetrazol. Increase in metallothionein and nitrotirosyne immunoreactivity of both seizures epilepsy models was observed.

Tissue-specific IL-10 secretion profile from term human fetal membranes stimulated with pathogenic microorganisms associated with preterm labor in a two-compartment tissue culture system.

Objective: Interleukin (IL)-10 is a cytokine with anti-inflammatory properties that plays pivotal roles in immune recognition and maintenance of pregnancy, limiting the harmful effects of pro-inflammatory modulators. The aim of this work was to characterize the contribution of amnion and choriodecidua regions of the human fetal membranes in the production of IL-10 after selective stimulation with Candida albicans, Gardnerella vaginalis and Streptococcus agalactiae.

Methods: Pre-labor human fetal membranes were cultured in a two-compartment tissue culture system and stimulated with 1 × 10(6) CFU/ml of each pathogen added to either the amniotic or choriodecidual region or both.

Progesterone elicits an inhibitory effect upon LPS-induced innate immune response in pre-labor human amniotic epithelium.

Problem: Infection of human fetal membranes elicits secretion of pro-inflammatory modulators through its innate immune capacities. We investigated the effect of lipopolysacharide (LPS) and progesterone (P4) upon expression of TLR-4/MyD88, TNFα, IL-6, IL-8, IL-10, and HBD2 on the human amniotic epithelium.

Method Of Study: Explants of the human amniotic epithelium were pre-treated with 0.

Tissue-specific human beta-defensins (HBD)-1, HBD-2 and HBD-3 secretion profile from human amniochorionic membranes stimulated with Candida albicans in a two-compartment tissue culture system.

Background: During intrauterine infection, amniochorionic membranes represent a mechanical and immunological barrier against dissemination of infection. Human beta defensins (HBD)-1, HBD-2, and HBD-3 are key elements of innate immunity that represent the first line of defense against different pathogen microorganisms associated with preterm labor. The aim of this work was to characterize the individual contribution of the amnion (AMN) and choriodecidua (CHD) regions to the secretion of HBD-1, HBD-2 and HBD-3, after stimulation with Candida albicans.

In vitro secretion profile of pro-inflammatory cytokines IL-1β, TNF-α, IL-6, and of human beta-defensins (HBD)-1, HBD-2, and HBD-3 from human chorioamniotic membranes after selective stimulation with Gardnerella vaginalis.

Problem: Preterm labor associated with infection is a major clinical condition; in this work, we analyze the response of human chorioamniotic membranes stimulated with Gardnerella vaginalis.

Method Of Study: Using a two-compartment experimental model, 1 × 10(6) CFU/mL of G. vaginalis were added to either the amnion or choriodecidua face or to both.

Evidence of in vitro differential secretion of human beta-defensins-1, -2, and -3 after selective exposure to Streptococcus agalactiae in human fetal membranes.

Objective: The aim of this work was to characterize the individual contribution of the amnion (AMN) and choriodecidua (CHD) regions to the secretion of human beta defensins (HBD)-1, -2, and -3, after stimulation with Streptococcus agalactiae.

Methods: Full-thickness membranes were mounted on a Transwell device, constituted by two independent chambers; 1 × 10(6) CFU/ml of S. agalactiae were added to either the AMN or CHD face or to both.

Tissue-specific human beta-defensins (HBD)1, HBD2, and HBD3 secretion from human extra-placental membranes stimulated with Escherichia coli.

Background: During an ascending infection along the reproductive tract, the extra-placental membranes must act as a selective and competent barrier against pathogens. Human beta defensins (HBD)1, HBD2, and HBD3 are key elements of innate immunity that are secreted to neutralize/control the progression of infection.

Methods: Full-thickness membranes were mounted on a Transwell device, constituted by two independent chambers, 1 × 10(6) CFU/ml of Escherichia coli were added to either the amnion (AMN) or the choriodecidual (CHD) face or to both.