Involvement of metalloproteinase and nitric oxide synthase/nitric oxide mechanisms in early decidual angiogenesis-vascularization of normal and experimental pathological mouse placenta related to maternal alcohol exposure.

Successful pregnancy for optimal fetal growth requires adequate early angiogenesis and remodeling of decidual spiral arterioles during placentation. Prior to the initiation of invasion and endothelial replacement by trophoblasts, interactions between decidual stromal cells and maternal leukocytes, such as uterine natural killer cells and macrophages, play crucial roles in the processes of early maternal vascularization, such as proliferation, apoptosis, migration, differentiation, and matrix and vessel remodeling. These placental angiogenic events are highly dependent on the coordination of several mechanisms at the early maternal-fetal interface, and one of them is the expression and activity of matrix metalloproteinases (MMPs) and endothelial nitric oxide synthases (NOSs).

Abnormal growth and morphogenesis of placenta at term is linked to adverse fetal development after perigestational alcohol consumption up to early gestation in mouse.

Background: Gestation alcohol consumption produces fetal growth restriction and malformations by affecting the embryo-fetal development. Recently a relationship between abnormal placentation and fetal malformation and intrauterine growth retardation has been suggested. However, the effects of perigestational alcohol ingestion up to early pregnancy on the placenta at term and its association with fetal abnormalities are little known.

Early Abnormal Placentation and Evidence of Vascular Endothelial Growth Factor System Dysregulation at the Feto-Maternal Interface After Periconceptional Alcohol Consumption.

Adequate placentation, placental tissue remodeling and vascularization is essential for the success of gestation and optimal fetal growth. Recently, it was suggested that abnormal placenta induced by maternal alcohol consumption may participate in fetal growth restriction and relevant clinical manifestations of the Fetal Alcohol Spectrum Disorders (FASD). Particularly, periconceptional alcohol consumption up to early gestation can alter placentation and angiogenesis that persists in pregnancy beyond the exposure period.

Comparative matrix metalloproteinase-2 and -9 expression and activity during endotheliochorial and hemochorial trophoblastic invasiveness.

To establish a functional placenta, its development needs adequate trophoblastic invasiveness. The intricate and complex morphological and molecular aspects regulating trophoblastic invasion during endotheliochorial placentation of domestic carnivores and their similarities and differences with the hemochorial placenta are still poorly understood. During placentation processes, from the time of implantation, trophoblast cells invade the uterine endometrium where they achieve extensive degradation and remodeling of extracellular matrix components; in this process, matrix metalloproteinases (MMPs), particularly MMP-2 and 9, have an essential role in rebuilding, cell migration, and invasiveness.

Perigestational alcohol consumption induces altered early placentation and organogenic embryo growth restriction by disruption of trophoblast angiogenic factors.

Research Question: Maternal alcohol consumption produces fetal retardation and malformations, probably associated with placental defects. Does perigestational alcohol consumption up to organogenesis lead to abnormal placentation and embryo growth restriction by disrupting the vascular endothelial growth factor (VEGF) system in embryo-placental development?

Design: Female mice were treated with 10% ethanol in drinking water before and up to day 10 of gestation. Control mice received ethanol-free water.

Decidual vascularization during organogenesis after perigestational alcohol ingestion.

Perigestational alcohol consumption up to early organogenesis can produce abnormal maternal vascularization via altered decidual VEGF/receptor expression. CF-1 female mice were administered with 10% ethanol in drinking water for 17 days prior to and up to day 10 of gestation. Control females received water without ethanol.

Murine sperm capacitation, oocyte penetration and decondensation following moderate alcohol intake.

Male chronic alcohol abuse causes testicular failure and infertility. We analyzed the effects of moderate sub-chronic alcohol intake on sperm morphology, capacitation, fertilization and sperm head decondensation. CF-1 male mice were administered 15% ethanol in drinking water for 15 days; control mice received ethanol-free water.

Cellular and molecular oxidative stress-related effects in uterine myometrial and trophoblast-decidual tissues after perigestational alcohol intake up to early mouse organogenesis.

The placenta plays a major role in embryo-fetal defects and intrauterine growth retardation after maternal alcohol consumption. Our aims were to determine the oxidative status and cellular and molecular oxidative stress effects on uterine myometrium and trophoblast-decidual tissue following perigestational alcohol intake at early organogenesis. CF-1 female mice were administered with 10% alcohol in drinking water for 17 days prior to and up to day 10 of gestation.

Oxidative stress and cellular and tissue damage in organogenic outbred mouse embryos after moderate perigestational alcohol intake.

Perigestational alcohol consumption by CF-1 mouse, from before mating up to the period of embryo organogenesis, leads to retarded early embryo development and neural tube defects. Here, we addressed if perigestational alcohol ingestion up to Day 10 of pregnancy induces oxidative stress and changes in macromolecules and organ tissues of early organogenic embryos. Adult CF-1 female mice were administered 10% ethanol in their drinking water for 17 days prior to mating and until Day 10 of gestation, whereas control females were administered ethanol-free water.

Differential expression and activity of matrix metalloproteinases 2 and 9 in canine early placenta.

The zonary and endotheliochorial dog placenta is the most invasive placenta of carnivores. The importance of matrix metalloproteinases (MMP) in placenta invasiveness has been determined in several mammals including species with haemochorial, epitheliochorial and endotheliochorial placentation. Regarding the latter, the expression of MMP enzymes has been studied in the cat and the mature canine placenta.

Arsenic trioxide alters the differentiation of mouse embryonic stem cell into cardiomyocytes.

Chronic arsenic exposure is associated with increased morbidity and mortality for cardiovascular diseases. Arsenic increases myocardial infarction mortality in young adulthood, suggesting that exposure during foetal life correlates with cardiac alterations emerging later. Here, we investigated the mechanisms of arsenic trioxide (ATO) cardiomyocytes disruption during their differentiation from mouse embryonic stem cells.

Peri-implantational in vivo and in vitro embryo-trophoblast development after perigestational alcohol exposure in the CD-1 mouse.

Long-term pregestational ethanol exposure induced altered fertilization and preimplantation embryogenesis. We evaluated preimplantational embryo-trophoblast differentiation, growth and invasiveness after perigestational ethanol 10% ingestion for 15 days preceding and up to day 4 (treated females [TF]: TF-D4 group) or 5 (TF-D5) of CD-1 gestation (control females [CF] with water). In TF-D4, expanded and hatched blastocyst numbers were significantly reduced (p < 0.

Matrix metalloproteinase expression and activity in trophoblast-decidual tissues at organogenesis in CF-1 mouse.

During early placentation, matrix metalloproteinases (MMPs) play important roles in decidualization, trophoblast migration, invasion, angiogenesis, vascularization and extracellular matrix (ECM) remodeling of the endometrium. The aim of our study was to analyze the localization, distribution and differential expression of MMP-2 and -9 in the organogenic implantation site and to evaluate in vivo and in vitro decidual MMP-2 and -9 activities on day 10 of gestation in CF-1 mouse. Whole extracts for Western blotting of organogenic E10-decidua expressed MMP-2 and -9 isoforms.

Embryo developmental disruption during organogenesis produced by CF-1 murine periconceptional alcohol consumption.

The aim was to study the control females (CF)-1 mouse embryo differentiation, growth, morphology on embryonic E- and N-cadherin expression at midgestation after periconceptional moderate alcohol ingestion. Adult female mice were exposed to 10% ethanol in drinking water for 17 days previous to and up to day 10 of gestation (ethanol-exposed females, EF) and were compared with nonexposed CF. EF presented reduced quantities of E10 to E10.

Male and female reproductive toxicity induced by sub-chronic ethanol exposure in CF-1 mice.

Since genetic damage induced by ethanol exposure is controversial and incomplete and because germ and somatic cells constitute bioindicators for monitoring reproductive toxicity and genotoxic actions of ethanol consumption, the purpose of the present investigation was to evaluate morphological sperm, oocyte alterations and parental genotoxic effects after sub-chronic ethanol intake in the CF-1 outbred mouse strain. Ethanol 10% was administered to CF-1 adult male (treated males, TM) and female (treated females, TF) mice for 27 days, whereas water was given to controls from both sexes too (CM and CF). Post-treatment micronucleus frequency (MN-PCE/1,000/mouse) and gamete morphology were evaluated.

IFPA Meeting 2010 Workshops Report II: Placental pathology; trophoblast invasion; fetal sex; parasites and the placenta; decidua and embryonic or fetal loss; trophoblast differentiation and syncytialisation.

Workshops are an important part of the IFPA annual meeting. At IFPA Meeting 2010 diverse topics were discussed in twelve themed workshops, six of which are summarized in this report. 1.

Changes in neostriatal and hippocampal synaptic densities in perinatal asphyctic male and female young rats: Role of hypothermia.

Perinatal asphyxia (PA) may cause long-term neurological and psychiatric diseases. We evaluated, by ethanolic phosphotungstic acid (E-PTA) staining, whether PA affects postsynaptic densities (PSDs), ultrastructure of neostriatum and hippocampus of 45-day-old post-PA male and female rats. PA was induced by placing the uterine horns containing the fetuses in a 37°C bath for 10, 15, 19 and 20 min and a 15°C bath for 20 min (hypothermia).

Interleukin-1 beta regulates metalloproteinase activity and leptin secretion in a cytotrophoblast model.

Implantation is one of the most regulated processes in human reproduction, by endocrine and immunological systems. Cytokines are involved in embryo-maternal communication and an impaired balance could result in pregnancy loss. Here we investigated the effect of interleukin 1-beta on the activity of two important metalloproteinases (MMP-2 and MMP-9) that are involved in extracellular matrix remodeling as well as the secretion of leptin, one of the reproductive hormones actively regulating their activity and secretion.

Interferon-gamma inhibits metalloproteinase activity and cytotrophoblast cell migration.

Problem: Establishment of a successful pregnancy relies on a complex fetal-mother communication that starts with the embryo adhering and invading the endometrium. This requires remodeling of extracellular matrix, performed by metalloproteinases. Cytokines, such as interferon-gamma (IFN-gamma), play a role in implantation and could affect the success of pregnancy.

Preimplantation embryotoxicity after mouse embryo exposition to reactive oxygen species.

Exposure of either gametes or embryos to conditions and/or factors that generate oxidative stress has been associated with impaired early embryogenesis. The effects of reactive oxygen species (ROS) on mouse preimplantation development, depending of the ROS-concentration and time of exposition, were studied. Two-cell embryos were incubated with 5, 10, 25 and 50 microM of hydrogen peroxide (H2O2) for 30 and 60 minutes of exposition and allowed to develop for 72 h to study the quality of development.

Periconceptional alcohol consumption-induced changes in embryonic prostaglandin E levels in mouse organogenesis: modulation by nitric oxide.

The mechanisms of the teratogenic effects of maternal alcohol consumption remain unclear. The aim of the present work was to study the organogenic PGE(2) levels and the modulation of PGE(2) levels by NO after periconceptional alcohol ingestion. Female mice were intoxicated with a 10% ethanol in drinking water before pregnancy and up to day 10 of gestation.

Neostriatal cytoskeleton changes following perinatal asphyxia: effect of hypothermia treatment.

Long-term changes of different types of neurofilaments (NF) and glial fibrillar acid protein (GFAP) were studied in neostriatal rat subjected to perinatal asphyxia (PA) under normothermic and hypothermic (15 degrees C) conditions, using immunohistochemistry for light and electron microscopy. Neostriatal neurons of 6-month-old rats that were subjected to 19 and 20 min of PA, showed an increase of NF 200 kDa immunostaining mainly in the axon fascicles in comparison with the control and hypothermia groups. In contrast, no alterations were seen with NF68 and NF160 neurofilament antibodies.

Effect of nutritional stress on the hypothalamo-pituitary-gonadal axis in the growing male rat.

Background/objective: Nutritional dwarfing (ND) consists of a decrease in weight and height gain and delayed onset of puberty. The aim of the present investigation was to study the modifications induced in male rats by the nutritional stress of a mere 20% reduction in food intake which, however, started immediately after weaning.

Materials And Methods: At weaning, male Wistar rats were divided into two groups: Control (C) and ND.