The effect of pre-partum shearing of Corriedale ewes on placental and lamb development and neonatal behaviour.

AIMS: To evaluate the effects of early and late pre-partum shearing of Corriedale ewes carrying single fetuses on placental and lamb development and neonatal lamb behaviour. METHODS: At 70 days of gestation, 37 multiparous Corriedale ewes with known gestation dates were randomly allocated into three groups: S70 (n = 12) and S110 (n = 12), shorn at Day 70 and 110 of gestation, and US (n = 13), that were not shorn pre-partum. Gestation length, lambing duration, placental expulsion time, placental weight, number and weight of cotyledons, and placental efficiency (lamb weight/placental weight) were determined. At birth, body temperature, weight, morphometric measurements, ponderal index (lamb weight/lamb crown-rump length) and behaviour were recorded, with weight remeasured 72 hours later. Four male lambs per group were slaughtered immediately after parturition, and organ weight and perirenal brown fat weight and energy content recorded. RESULTS: Pre-partum shearing, regardless of timing, increased total dried placental weight per ewe. Pre-partum shearing at Day 70 of gestation increased the number and mean weight of the > 2 to ≤ 3-cm cotyledons, while pre-partum shearing at Day 110 of gestation increased only the weight of these cotyledons. At birth and at 72 hours, lambs from ewes shorn either at 70 days of gestation (birth: 5.5 (95% CI = 4.6-6.4) kg, p = 0.001; 72 hours: 6.4 (95% CI = 6.1-6.8) kg, p = 0.002) or at 110 days of gestation (birth: 5.4 (95% CI = 4.4-6.4) kg, p = 0.001; 72 hours: 6.5 (95% CI = 5.9-7.1) kg, p = 0.001) were heavier than lambs from unshorn ewes (birth: 4.0 (95% CI = 3.3-4.8) kg; 72 hours: 4.8 (95% CI = 3.5-6.1) kg). Lambs born to S70 and S110 ewes suckled sooner (31.5 (95% CI = 14.5-48.5) minutes, p = 0.001; and 39.3 (95% CI = 23.7-55.0) minutes, p = 0.001 respectively), than lambs born to the US group (70.3 (95% CI = 38.6-102.1) minutes). There was no evidence for an effect of pre-partum shearing on gestation length, parturition length, time of placental expulsion, placental efficiency, weight and energy of perirenal brown fat, and lamb temperature at birth. CONCLUSIONS AND CLINICAL RELEVANCE: Shearing ewes pre-partum may lead to placental changes affecting lamb development and behaviour and associated with higher survival. The findings suggest pre-partum shearing may improve lamb survival, farm profitability and sustainability.

The structure of the porcine uterine-conceptus interface is associated with gestational day, fetal size and sex.

This study aimed to characterize histological changes of the maternal-conceptus interface in feto-placental units associated with fetal weight and sex throughout pregnancy. Pregnant Large-White X Landrace gilts(n=18) were euthanized and hysterectomized on gestational days[GDs] 30(n=3), 45(n=5), 60(n=5), and 90(n=5). Intact cross-sections of fetoplacental interface associated with the lightest[LW] and normally-grown[NW] littermates were collected on GD30(n=4 per size). On GDs 45, 60 and 90, interactions between fetal size and sex were investigated in light-weight males[LWM] and females[LWF]; normal-weight males[NWM] and females[NWF] (n=4/group/GD). Fetal weight did not affect the endometrium composition, including relative proportion of glandular epithelium, blood vessels, and connective tissue. Feto-placental units from LW embryos tended to have longer chorioallantoic fold length on GD30(P=0.06). On GD45, higher proportion of larger endometrial glands was observed in NWM, and taller trophoblastic epithelium in NW conceptuses, regardless of sex(P<0.05). NWF presented the greatest proportion of subluminal endometrial epithelial blood vessels(P<0.05). On GD60, more blood vessels were present at the folds' base in males feto-placental units, whereas taller trophoblastic epithelium were present in NWF fetuses' feto-placental units(P<0.05). Feto-placental units' morphological composition throughout gestation in NW and LW conceptuses revealed that fold length was higher as early as GD30, with no further increase up to GD90 in LW conceptuses(P>0.05). Increased proportion of glandular epithelium was observed in LW conceptuses; the highest percentage present on GD90(P<0.05). Collectively, we demonstrated that fetal weight and sex influence the morphological structure of feto-placental units from as early as GD30, suggesting potential differences in the ability for nutrient transport.

Polystyrene microplastics exposition on human placental explants induces time-dependent cytotoxicity, oxidative stress and metabolic alterations.

Introduction: Microplastics (MPs) are environmental pollutants that pose potential risks to living organisms. MPs have been shown to accumulate in human organs, including the placenta. In this study, we investigated the biochemical impact of 5 µm polystyrene microplastics (PS-MPs) on term placental chorionic villi explants, focusing on cytotoxicity, oxidative stress, metabolic changes, and the potential for MPs to cross the placental barrier. Methods: Term placental chorionic explants were cultured for 24 hours with varying concentrations of PS-MPs, with MTT assays used to determine the appropriate concentration for further analysis. Cytotoxicity was assessed using the lactate dehydrogenase (LDH) release assay over a period of up to 72 hours. Reactive oxygen species formation and antioxidant activity were evaluated using biochemical assays. Metabolomic profiling was performed using proton nuclear magnetic resonance (1H NMR). Results: Placental explants exposed to 100 µg/mL of PS-MPs showed a significant increase in cytotoxicity over time (p < 0.01). Levels of mitochondrial and total superoxide anion (p < 0.01 and p < 0.05, respectively) and hydrogen peroxide (p < 0.001) were significantly elevated. PS-MP exposure resulted in a reduction in total sulfhydryl content (p < 0.05) and the activities of antioxidant enzymes superoxide dismutase (p < 0.01) and catalase (p < 0.05), while glutathione peroxidase activity increased (p < 0.05), and the oxidized/reduced glutathione ratio decreased (p < 0.05). Markers of oxidative damage, such as malondialdehyde and carbonylated proteins, also increased significantly (p < 0.001 and p < 0.01, respectively), confirming oxidative stress. Metabolomic analysis revealed significant differences between control and PS-MP-exposed groups, with reduced levels of alanine, formate, glutaric acid, and maltotriose after PS-MP exposure. Discussion: This study demonstrates that high concentrations of PS-MPs induce time-dependent cytotoxicity, oxidative stress, and alterations in the TCA cycle, as well as in folate, amino acid, and energy metabolism. These findings highlight the need for further research to clarify the full impact of MP contamination on pregnancy and its implications for future generations.

Galectin-3 plays a key role in controlling infection by Toxoplasma gondii in human trophoblast cells and human villous explants.

Galectin-3 (Gal-3) is a ß-galactoside-binding lectin expressed in cells of the placental microenvironment. This lectin is involved in various biological processes, such as modulation of the immune system and control of parasitic illness. Toxoplasma gondii infection can lead to congenital transmission and cause miscarriages, prematurity and fetal anomalies. However, little is known about the role of Gal-3 in T. gondii infection in the placental microenvironment. This study aimed to unravel the underlying mechanisms of Gal-3 during T. gondii infection. For this purpose, we promoted the knockdown of Gal-3 expression by using RNA interference (RNAi) in BeWo cells or by using a synthetic inhibitor (GB1107) in human villous explants. We showed that the decreased Gal-3 expression in BeWo cells and human villous explants increases the invasion and proliferation of T. gondii probably by downregulating MIF and IL6 levels, highlighting thus the role of this lectin in modulating the immune response. Collectively, our study reveals Gal-3 as a promising target protein during congenital toxoplasmosis.

Glycosylation in Canine Placentas.

This article describes the carbohydrate composition of early and mature placentas from bitches, detected by lectin histochemistry. Formalin-fixed placental samples from 11 mixed-breed bitches have been assigned to the 'early' or the 'mature' placenta group, processed by the routine histological technique and labelled with a panel of 14 biotinylated lectins. The glycan distribution was almost completely preserved over pregnancy. Cytotrophoblast cells expressed high-mannose N-linked residues and N-acetyl-D-glucosamine, whereas mannose N-linked residues, N-acetyl-D-glucosamine and ß- and α-D-galactose/N-acetyl-D-galactosamine have been found in the syncytiotrophoblast. The maternal and foetal endothelial binding pattern was enriched in ß-D-galactose, α-D-mannose in non-bisected bi/tri-antennary N-linked complex and Galα1,3Gal-Galα1,4Gal. Both deep and superficial glands showed a great variety of glycoconjugates, such as D-mannose, D-glucose, N-acetyl-D-glucosamine, N-acetyl-D-galactosamine, galactose, N-acetylneuraminic acid and fucose. Most results in this study were consistent with those previously reported in canine and feline mature placentas; here, early placentas have been analysed and the lectin binding pattern of mature placentas has been further described. These studies on canine placentas contribute to detecting and understanding glycome changes in pathophysiological conditions.

The autophagy process and oxidized LDL independently modulate the invasion and differentiation of extravillous trophoblastic cells to an endothelial-like phenotype in normoxia.

INTRODUCTION: The mechanisms leading to proper placentation are not fully understood. Extravillous trophoblasts (EVTs) are crucial for placentation through invasion and vascular remodeling, which, when impaired, promote a poor placentation. How autophagy could regulate EVTs function and the study of regulators of these processes, such as oxidized low-density lipoproteins (ox-LDL), could contribute to better understand events associated with pregnancy complications related to abnormal placental development, such as preeclampsia (PE). AIM: To investigate the role of autophagy and oxidized LDL (ox-LDL) in invasion and endothelial-like phenotype acquisition of a model of EVTs, as well as to determine the levels of autophagy flux markers in control and PE placentas. METHODS: Invasion and endothelial-like phenotype acquisition assays were performed in a cell line model of first trimester EVTs: HTR-8/SVneo cultured in normoxia (oxygen concentration of 20 %), in the absence or the presence of the autophagy inhibitor bafilomycin or/and ox-LDL. Markers of autophagic flux were evaluated in human term placentas. RESULTS: Autophagy is essential for EVTs to acquire an endothelial-like phenotype but does not affect invasion. Conversely, ox-LDL decreases invasion and reticular structures formation, independent of autophagy. At pregnancy term, the levels of the autophagy markers LC3 and p62 are deregulated in the trophoblast cells of PE placentas. CONCLUSION: Autophagy is necessary for proper endothelial-like phenotype acquisition in HTR-8/SVneo cultured in normoxia, and ox-LDL impairs this process as well as the invasion of EVTs by a mechanism independent of autophagy. Changes in autophagy and/or in the concentration of ox-LDL could affect placental vascular remodeling.

Influence of maternal hyperglycemia on placental capillary distribution.

OBJECTIVE: This study was conducted to investigate the distribution of placental villous vessels in pregnant women with different degrees of hyperglycemia. METHODS: A cross-sectional study was performed using placental samples from 30 pregnant women without diabetes (n=10), with gestational diabetes mellitus (n=10), and with previous diabetes (type 1 and type 2 diabetes; n=10). Maternal glycemic control was evaluated using the glycemic mean and glycated hemoglobin levels. Placental samples were obtained during elective cesarean sections and processed for villous vessel analysis using immunohistochemistry for Von Willebrand factor. Vessels within 10µm of the villus margin were classified as peripheral, and vessels at a distance greater than 10µm were classified as central. The number, area, and perimeter of all vessels were evaluated, and the relationship between vessel area and total area of placental villus was calculated. RESULTS: Pregnant women with gestational diabetes mellitus and those with previous diabetes had higher glycated hemoglobin levels. The number of vessels was reduced in the villi of the previous Diabetes Group owing to peripheral reduction. Additionally, the area, perimeter, and percentage of peripheral blood were lower in the previous Diabetes Group than in the Non-Diabetic Group. CONCLUSION: Maternal glycemic levels can modify placental capillary distribution.

Moreli et al. demonstrated a reduction in vessels in the periphery of the placental villi in pregnant women with previous diabetes (type 1 and type 2). The placental vessels of this population are more distant from the maternal blood and may represent placental villous immaturity. These results were obtained when we classified the villous vessels as central or peripherial using 10µm of the villus margin as a reference.

■The number of vessels was reduced in the placental villi of pregnant women with diabetes. ■The placental villous vessels of women with previous diabetes were more distant from the maternal blood.

Maternal-Fetal Blood Flow and Progesterone Concentration in Ewes Sheared at Mid or Late-Pregnancy.

These studies aimed to determine if shearing ewes at the second or last third of gestation modify the uterine and placentome blood flow, placentome size, and maternal progesterone concentration. Pregnant ewes were assigned to four groups of 12 ewes each according to the gestation period: mid-pregnancy sheared (on day 90 of pregnancy) or unshorn group; and late-pregnancy sheared group (on day 121 of pregnancy) or unshorn group. In both experimental periods, using spectral Doppler ultrasonography, placentomes and uterine artery blood flow and placentome size were evaluated 14 days before and 6 days after shearing. An additional measurement was performed 26 days after shearing in mid-pregnant ewes. Serum progesterone concentration was measured before shearing 4, 24, 72 h, and 22 days after shearing. The uterine artery's end-diastolic velocity (EDV) tended to be greater in the sheared than in the non-sheared ewes (p = 0.1). Peak systolic velocity (PSV) and EDV of placentome increased (p = 0.05 and p = 0.008, respectively) on day 26, accompanied by an increase in placentome area (p = 0.035) in mid-pregnant ewes. In late-pregnant ewes, uterine artery and placentome blood flow and size did not vary. Progesterone concentration varied with time but was not affected by shearing. In conclusion, shearing triggered an increase in placentome size and some changes in blood flow only when ewes were sheared during the second third of their pregnancy. Shearing ewes either the second or last third of gestation did not affect uterine artery blood flow and progesterone secretion.

Enrichment of trimethyl histone 3 lysine 4 in the Dlk1 and Grb10 genes affects pregnancy outcomes due to dietary manipulation of excess folic acid and low vitamin B12.

The aberrant expression of placental imprinted genes due to epigenetic alterations during pregnancy can impact fetal development. We investigated the impact of dietary modification of low vitamin B12 with varying doses of folic acid on the epigenetic control of imprinted genes and fetal development using a transgenerational model of C57BL/6J mice. The animals were kept on four distinct dietary combinations based on low vitamin B12 levels and modulated folic acid, mated in the F0 generation within each group. In the F1 generation, each group of mice is split into two subgroups; the sustained group was kept on the same diet, while the transient group was fed a regular control diet. After mating, maternal placenta (F1) and fetal tissues (F2) were isolated on day 20 of gestation. We observed a generation-wise opposite promoter CpG methylation and gene expression trend of the two developmental genes Dlk1 and Grb10, with enhanced gene expression in both the sustained and transient experimental groups in F1 placentae. When fetal development characteristics and gene expression were correlated, there was a substantial negative association between placental weight and Dlk1 expression (r = - 0.49, p < 0.05) and between crown-rump length and Grb10 expression (r = - 0.501, p < 0.05) in fetuses of the F2 generation. Consistent with these results, we also found that H3K4me3 at the promoter level of these genes is negatively associated with all fetal growth parameters. Overall, our findings suggest that balancing vitamin B12 and folic acid levels is important for maintaining the transcriptional status of imprinted genes and fetal development.

Partial biochemical and immunological characterization of an isolated 52.1 kDa pregnancy-associated glycoprotein charge variant.

Pregnancy-associated glycoproteins (PAGs) are synthesized in the placental cells of ruminants and are detectable in blood, milk, and urine. Many of these proteins have been obtained and characterized from placental extracts by precipitation with 80 % ammonium sulfate. The possibility of purifying PAGs by precipitation with other concentrations of ammonium sulfate remains unexplored. We aimed to study PAG proteins obtained from extracts of ovine placenta at 100 days of gestation through precipitation with 40 % ammonium sulfate (Extract 40). The main protein complex (130 kDa) was obtained after Extract 40 precipitation. Under reducing SDS-PAGE conditions, the 130 kDa complex dissociated in two PAG proteins with apparent molecular weights of 52.1 kDa and 26.1 kDa. The 130 kDa protein appeared to be a molecular complex consisting of two copies of the 52.1 kDa protein linked to one copy of the 26.1 kDa protein, presumably by disulfide bonds. Furthermore, the 52.1 kDa protein consisted of at least three isoforms with distinct isoelectric points. Amino acid microsequencing of the 52.1 kDa protein revealed a chimeric structure containing amino acid sequences of PAG1, PAG4, PAG6, and PAG1-like proteins. This procedure recovered a novel 130 kDa protein complex composed of 26.1 kDa and two 52.1 kDa PAGs. To the best of our knowledge, this has not been previously reported as heterologous polymeric molecules.

Maternal alcohol consumption up to mouse organogenesis disrupts fetal-placental interface at mid-gestation associated with dysregulation of AQP3 immunoexpression.

Adequate trophoblast development during placentation involves the AQP3 regulation. The link between potential placental fetal-maternal interface abnormalities and AQP3 expression after perigestational alcohol intake was not explored yet. Female mice were treated (TF) with 10 % ethanol in drinking water before and up to day 10 of gestation, and control females (CF) with ethanol-free water. At gestational day 13, TFs showed increased fetal/placental weight ratio and reduced histological placental thickness compared to CFs. TF-placentas had disorganized fetal face layers, increased junctional zone (JZ), and decreased labyrinth (Lab). Concomitantly, immunoexpression of cleaved caspase-3 significantly increased in TF-JZ and Lab vs controls. Consistent with placental changes, AQP3 expression was higher in junctional trophoblast giant cells (TGCs), glycogen cells (GCs), spongiotrophoblasts (spg), and lab-syncytiotrophoblasts compared to CF-placentas. This study reveals, for the first time, that perigestational alcohol consumption up to organogenesis causes abnormal placental development associated with dysregulation of AQP3 expression.

Sex-specific phenotypical, functional and metabolic profiles of human term placenta macrophages.

BACKGROUND: Placental macrophages, Hofbauer cells (HBC) are the only fetal immune cell population within the stroma of healthy placenta along pregnancy. They are central players in maintaining immune tolerance during pregnancy. Immunometabolism emerged a few years ago as a new field that integrates cellular metabolism with immune responses, however, the immunometabolism of HBC has not been explored yet. Here we studied the sex-specific differences in the phenotypic, functional and immunometabolic profile of HBC. METHODS: HBC were isolated from human term placentas (N = 31, 16 from male and 15 female neonates). Ex vivo assays were carried out to assess active metabolic and endoplasmic reticulum stress pathways by flow cytometry, confocal microscopy, gene expression and in silico approaches. RESULTS: HBC from female placentas displayed a stronger M2 phenotype accompanied by high rates of efferocytosis majorly sustained on lipid metabolism. On the other hand, male HBC expressed a weaker M2 phenotype with higher glycolytic metabolism. LPS stimulation reinforced the glycolytic metabolism in male but not in female HBC. Physiological endoplasmic reticulum stress activates IRE-1 differently, since its pharmacological inhibition increased lipid mobilization, accumulation and efferocytosis only in female HBC. Moreover, differential sex-associated pathways accompanying the phenotypic and functional profiles of HBC appeared related to the placental villi environment. CONCLUSIONS: These results support sex-associated effects on the immunometabolism of the HBC and adds another layer of complexity to the intricate maternal-fetal immune interaction.

Placental macrophages are the only fetal immune cell population within the stroma of healthy placenta along pregnancy and play a central role in contributing to the correct functioning of the placenta for the development of the fetus. Alterations in their metabolism lead to failures in their functions which are associated to pregnancy complications. Although, sex-specific differences were found in placental adaptation to pregnancy complications and outcomes, but the metabolism associated to their functions of placenta macrophages and whether they are associated to the sex of the placenta have not been explored so far. Here we studied human term placenta macrophages with special focus on their metabolism associated with their functions. We found out that macrophages from female placenta got energy from fatty acids whereas male macrophages used glucose. Furthermore, when female macrophages were exposed to a bacterial component, their metabolism or cellular function did not change towards one associated with a classic profile, but male macrophages did. These results might contribute to gain more insight into the immune-placental interactions at term human pregnancy and provide new clues to begin personalizing the pregnancy according to the sex of the fetus in physiological or pregnancy complications of inflammatory nature.

Trypanosoma cruzi-derived exovesicles contribute to parasite infection, tissue damage, and apoptotic cell death during ex vivo infection of human placental explants.

Trypanosoma cruzi, the causative agent of Chagas disease, can be congenitally transmitted by crossing the placental barrier. This study investigates the role of T. cruzi-derived exovesicles (TcEVs) in facilitating parasite infection and the consequent tissue damage and apoptotic cell death in human placental explants (HPEs). Our findings demonstrate that TcEVs significantly enhance the parasite load and induce tissue damage in HPEs, both in the presence and absence of the parasite. Through histopathological and immunohistochemical analyses, we show that TcEVs alone can disrupt the placental barrier, affecting the basal membrane and villous stroma. The induction of apoptotic cell death is evidenced by DNA fragmentation, caspase 8 and 3, and p18 fragment immunodetection. This damage is exacerbated when TcEVs are combined with T. cruzi infection. These findings suggest that TcEVs play a critical role in the pathogenesis of congenital Chagas disease by disrupting the placental barrier and facilitating parasite transmission to the fetus. This study provides new insights into the mechanisms of transplacental transmission of T. cruzi and highlights the potential of targeting TcEVs as a therapeutic strategy against congenital Chagas disease.

hsa-miR-582-3p in umbilical cord blood is negatively associated with maternal exposure to childhood maltreatment.

Aim: Childhood maltreatment (CM) may affect not only directly exposed individuals but also their offspring. However, the underlying biological mechanisms remain unclear. microRNAs (miRNAs) may play a regulatory role in this process. This study investigates the relationship between maternal exposure to CM and miRNA expression in maternal and perinatal tissues.Methods: We enrolled 43 pregnant women and assessed their CM exposure. We collected maternal blood, cord blood and placental tissue samples during childbirth and performed miRNA profiling using next generation sequencing.Results: Maternal CM was inversely associated with hsa-miR-582-3p levels in cord blood. Pathway analysis revealed that this miRNA regulates genes involved in intrauterine development.Conclusion: Our findings highlight the potential impact of maternal CM exposure on offspring epigenetic mechanisms.

Child maltreatment (CM) includes physical, sexual and emotional abuse, as well as physical and emotional neglect. CM not only harms those directly exposed but can also negatively impact their offspring. However, the biological reasons behind this are not well understood. To explore this further, our study investigates how CM affects the biology of pregnant women and their newborns through changes in small regulatory molecules called microRNAs (miRNAs). We recruited 43 pregnant women and assessed their exposure to CM. During childbirth, we collected blood samples from the mothers, blood from the umbilical cord and placental samples. We then analyzed the levels of miRNAs in these samples using advanced sequencing technology. We observed that more severe maternal exposure to CM was associated with lower levels of a miRNA named hsa-miR-582-3p in umbilical cord blood. This miRNA regulates genes involved in fetal development in utero and has been linked to spontaneous preterm birth. It may also influence immunologic and stress-related processes. Thus, newborns of mothers who had been exposed to CM may be more vulnerable to adverse effects on their brain development and overall health. Despite our small sample size, our study highlights the importance of addressing CM as an intergenerational concern and provides new insights into the biological mechanisms through which maternal CM can affect offspring.

Impaired Endothelium-Dependent Vasodilation and Increased Levels of Soluble Fms-like Tyrosine Kinase-1 Induced by Reduced Uterine Perfusion Pressure in Pregnant Rats: Evidence of Protective Effects with Sodium Nitrite Treatment in Preeclampsia.

Preeclampsia (PE) is a hypertensive disorder of pregnancy and is associated with increases in soluble fms-like tyrosine kinase-1 (sFlt-1) and reductions in nitric oxide (NO) levels. Placental ischemia and hypoxia are hypothesized as initial pathophysiological events of PE. Nitrite (NO metabolite) may be recycled back to NO in ischemic and hypoxic tissues. Therefore, this study examined the sodium nitrite effects in an experimental model of PE. Pregnant rats received saline (Preg group) or sodium nitrite (Preg + Na-Nitrite group). Pregnant rats submitted to the placental ischemia received saline (RUPP group) or sodium nitrite (RUPP + Na-Nitrite group). Blood pressure, placental and fetal weights, and the number of pups were recorded. Plasma levels of NO metabolites and sFlt-1 were also determined. Vascular and endothelial functions were also measured. Blood pressure, placental and fetal weights, the number of pups, NO metabolites, sFlt-1 levels, vascular contraction, and endothelium-dependent vasodilation in the RUPP + Na-Nitrite rats were brought to levels comparable to those in Preg rats. In conclusion, sodium nitrite may counteract the reductions in NO and increases in sFlt-1 levels induced by the placental ischemia model of PE, thus suggesting that increased blood pressure and vascular and endothelial dysfunctions may be attenuated by sodium nitrite-derived NO.

Improvement of motor function in mice after implantation of mononuclear stem cells from human umbilical cord and placenta blood after 3 and 6 weeks of experimental spinal cord injury.

STUDY DESIGN: Experimental study utilizing with a standardized model (MASCIS Impactor) of Spinal Cord Injury (SCI) in Balb C mouse model with implantation of mononuclear stem cells derived from the human umbilical cord and placenta blood in the early chronic phase of SCI. OBJECTIVES: The aim of this study was to evaluate the nerve regeneration and motor functional recovery in Balb C mice with surgically induced paraplegia in response to the use of mononuclear stem cells, in early chronic phase (> 2 weeks and < 6 months), because there is yet potential of neuronal and functional recovery as the neuronal scar is not still completely established. METHODS: Forty-eight mice were randomly assigned to 6 groups of 8 animals. Group 1 received the stem cells 3 weeks after the trauma, and Group 2 received them six weeks later. In Group 3, saline solution was injected at the site of the lesion 3 weeks after the trauma, and in Group 4, 6 weeks later. Group 5 underwent only spinal cord injury and Group 6 underwent laminectomy only. The scales used for motor assessment were BMS and MFS for 12 weeks. RESULTS: The intervention groups showed statistically significant motor improvement. In the histopathological analysis, the intervention groups had a lower degree of injury (p < 0.05). Regarding axonal budding, the intervention groups showed increasing in axonal budding in the caudal portion (p < 0.05). CONCLUSIONS: The use of stem cells in mice in the chronic phase after 3 and 6 weeks of SCI brings functional and histopathological benefits to them.

Placenta as a source of autologous graft in postnatal correction of myelomeningocele.

OBJECTIVE: This integrative literature review aims to discuss the benefits and limitations of postnatal surgery to correct myelomeningocele using the placenta as an autologous graft used on the lesion; in addition, it seeks to highlight the placental properties and the benefits and indications of surgery. METHODS: For this production, the PRISMA criteria were used. PubMed was used as a database on October 19, 2023, and three searches were made, all using the words "myelomeningocele" and "surgery" varying only between "amnion," "placenta," and "chorion" as the third word. A total of 91 articles were found, and after analysis of duplicates and inclusion and exclusion criteria, only 11 articles were used in this systematic review. RESULTS: Properties of the amniotic membrane were observed, such as anti-inflammatory, stimulation of native tissue growth, regenerating action by the secretion of neutrophil factors, promotion of epithelialization, inhibition of fibrosis and healing, and antibacterial effect. It is observed that there are benefits in using the placenta as an autograft and there are contradictions between the periods of surgery. CONCLUSION: Due to its properties that accelerate healing, the absence of the possibility of rejection, and its easy access make this choice more frequently adopted. We are confident in saying that the effectiveness of the amniotic membrane is widely reliable.

Expression levels of ACE and ACE2 in the placenta and white adipose tissue of lean and obese pregnant women.

BACKGROUND: This study evaluated the expression of ACE and ACE2 in the placenta and white adipose tissue in lean and obese women, and correlated their levels with anthropometric, clinical, and laboratory parameters, and tissue count of inflammatory cells. METHODS: A cross-sectional analytical study was performed with 49 pregnant women and their respective newborns. Samples of placenta and adipose tissue were used for measuring mRNA expression for ACE and ACE2 through qRT-PCR. Inflammatory cell counting was performed through conventional microscopy. RESULTS: An increase in ACE expression and a decrease in ACE2 were observed in the placenta and adipose tissue of women with obesity. ACE2 levels showed a negative correlation with pre-pregnancy BMI and total cholesterol. CONCLUSION: Maternal obesity can modulate the expression of RAS components in the placenta and white adipose tissue, with ACE2 correlated with pre-pregnancy BMI and total cholesterol.

Preeclampsia and transport of ions and small molecules: A literature review.

Preeclampsia (PE) is a prevalent obstetric complication affecting approximately 3-5% of pregnancies worldwide and is a major cause of maternal and perinatal morbidity and mortality. Preeclampsia is considered a disease of the endothelial system that can progress to eclampsia, characterized by seizures. Early diagnosis and appropriate management are crucial to improving maternal and fetal outcomes, as preeclampsia can lead to severe complications such as placental abruption, fetal growth restriction, and stroke. The pathophysiology of PE is complex, involving a combination of genetic, acquired, and immunological factors. A central feature of the condition is inadequate placentation and impaired uteroplacental perfusion, leading to local hypoxia, endothelial dysfunction, vasoconstriction, and immunological dysregulation. Recent evidence suggests that dysregulation of ion transporters may play a significant role in the adaptation of uterine circulation during placentation. These transporters are essential for maintaining maternal-fetal homeostasis, influencing processes such as nutrient exchange, hormone synthesis, trophoblast cell migration, and the function of smooth muscle cells in blood vessels. In preeclampsia, adverse conditions like hypoxia and oxidative stress result in the downregulation of ion, solute, and water transporters, impairing their function. This review focuses on membrane transporters involved in PE, discussing functional alterations and their physiological implications. The goal of this investigation is to enhance understanding of how dysregulation of ion and small molecule transporters contributes to the development and progression of preeclampsia, underscoring the importance of exploring these signaling pathways for potential therapeutic interventions.

The Relationship between HERV, Interleukin, and Transcription Factor Expression in ZIKV Infected versus Uninfected Trophoblastic Cells.

Zika virus (ZIKV) is an arbovirus with maternal, sexual, and TORCH-related transmission capabilities. After 2015, Brazil had the highest number of ZIVK-infected pregnant women who lost their babies or delivered them with Congenital ZIKV Syndrome (CZS). ZIKV triggers an immune defense in the placenta. This immune response counts with the participation of interleukins and transcription factors. Additionally, it has the potential involvement of human endogenous retroviruses (HERVS). Interleukins are immune response regulators that aid immune tolerance and support syncytial structure development in the placenta, where syncytin receptors facilitate vital cell-to-cell fusion events. HERVs are remnants of ancient viral infections that integrate into the genome and produce syncytin proteins crucial for placental development. Since ZIKV can infect trophoblast cells, we analyzed the relationship between ZIKV infection, HERV, interleukin, and transcription factor modulations in the placenta. To investigate the impact of ZIKV on trophoblast cells, we examined two cell types (BeWo and HTR8) infected with ZIKV-MR766 (African) and ZIKV-IEC-Paraíba (Asian-Brazilian) using Taqman and RT2 Profiler PCR Array assays. Our results indicate that early ZIKV infection (24-72 h) does not induce differential interleukins, transcription factors, and HERV expression. However, we show that the expression of a few of these host defense genes appears to be linked independently of ZIKV infection. Future studies involving additional trophoblastic cell lineages and extended infection timelines will illuminate the dynamic interplay between ZIKV, HERVs, interleukins, and transcription factors in the placenta.