RESUMO

Glucocorticoids (GCs) are steroid hormones fundamental to the body's normal physiological functions and are pivotal in fetal growth and development. During gestation, the mother's cortisol concentration (active GCs) escalates to accommodate the requirements of fetal organ development and maturation. A natural placental GCs barrier, primarily facilitated by 11ß hydroxysteroid dehydrogenase 2, exists between the mother and fetus. This enzyme transforms biologically active cortisol into biologically inactive corticosterone, thereby mitigating fetal GCs exposure. However, during pregnancy, the mother may be vulnerable to adverse factor exposures such as stress, hypoxia, caffeine, and synthetic GCs use. In these instances, maternal serum GCs levels may surge beyond the protective capacity of the placental GCs barrier. Moreover, these adverse factors could directly compromise the placental GCs barrier, resulting in excessive fetal exposure to GCs. It is well-documented that prenatal GCs exposure can detrimentally impact the offspring's cardiovascular system, particularly in relation to blood pressure, vascular function, and heart function. In this review, we succinctly delineate the alterations in GCs levels during pregnancy and the potential mechanisms driving these changes, and also analyze the possible causes of prenatal GCs exposure. Furthermore, we summarize the current advancements in understanding the adverse effects and mechanisms of prenatal GCs exposure on the offspring's cardiovascular system.

Assuntos

Glucocorticoides , Efeitos Tardios da Exposição Pré-Natal , Gravidez , Humanos , Feminino , Glucocorticoides/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Animais , Sistema Cardiovascular/efeitos dos fármacos , Sistema Cardiovascular/metabolismo , Doenças Cardiovasculares/induzido quimicamente , Desenvolvimento Fetal/efeitos dos fármacos , Placenta/metabolismo , Placenta/efeitos dos fármacos

RESUMO

Microplastics (MPs), a brand-new class of worldwide environmental pollutant, have received a lot of attention. MPs are consumed by both humans and animals through water, food chain and other ways, which may cause potential health risks. However, the effects of MPs on embryonic development, especially placental function, and its related mechanisms still need to be further studied. We investigated the impact on fetal development and placental physiological function of pregnant mice by consecutive gavages of MPs at 0, 25, 50, 100 mg/kg body weight during gestational days (GDs 0-14). The results showed that continuous exposure to high concentrations of MP significantly reduced daily weight gain and impaired reproductive performance of pregnant mice. In addition, MPs could significantly induce oxidative stress and placental dysfunction in pregnant mice. On the other hand, MPs exposure significantly decreased placental barrier function and induced placental inflammation. Specifically, MPs treatment significantly reduced the expression of tight junction proteins in placentas, accompanied by inflammatory cell infiltration and increased mRNA levels of pro-inflammatory cytokines and chemokines in placentas. Finally, we found that MPs induced placental apoptosis and endoplasmic reticulum (ER) stress through the GRP78/IRE1α/JNK axis, leading to placental dysfunction and decreased reproductive performance in pregnant mice. We revealed for the first time that the effects of MPs on placental dysfunction in pregnant animals. Blocking the targets of MPs mediated ER stress will provide potential therapeutic ideas for the toxic effects of MPs on maternal pregnancy.

Assuntos

Apoptose , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático , Microplásticos , Placenta , Animais , Feminino , Gravidez , Chaperona BiP do Retículo Endoplasmático/metabolismo , Apoptose/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Placenta/efeitos dos fármacos , Placenta/metabolismo , Microplásticos/toxicidade , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas de Choque Térmico/metabolismo , Proteínas de Choque Térmico/genética , Retardo do Crescimento Fetal/induzido quimicamente , Camundongos Endogâmicos ICR

RESUMO

To assess the impact of postnatal processing on placental DNA methylation, array data from flash-frozen placental tissue was compared to perfluorocarbon-immersed and formalin-fixed paraffin-embedded placental tissue. We observed that tissue exposed to perfluorocarbon showed no significant DNA methylation differences when compared to unprocessed tissue, while formalin processing altered the quality and reliability of the data produced on the DNA methylation array platform. Placental DNA methylation allows for the study of gene-environment interactions that influence the fetal environment and development. Our study highlights that placental post-processing techniques must be considered in the evaluation and interpretation of epigenetic studies.

Assuntos

Metilação de DNA , Placenta , Humanos , Metilação de DNA/genética , Feminino , Placenta/metabolismo , Gravidez , Epigênese Genética/genética , Inclusão em Parafina/métodos , Epigenômica/métodos

RESUMO

The placenta plays a crucial role in protecting the fetus from environmental harm and supports the development of its brain. In fact, compromised placental function could predispose an individual to neurodevelopmental disorders. Placental epigenetic modifications, including DNA methylation, could be considered a proxy of placental function and thus plausible mediators of the association between intrauterine environmental exposures and genetics, and childhood and adult mental health. Although neurodevelopmental disorders such as autism spectrum disorder have been investigated in relation to placenta DNA methylation, no studies have addressed the association between placenta DNA methylation and child's cognitive functions. Thus, our goal here was to investigate whether the placental DNA methylation profile measured using the Illumina EPIC array is associated with three different cognitive domains (namely verbal score, perceptive performance score, and general cognitive score) assessed by the McCarthy Scales of Children's functions in childhood at age 4. To this end, we conducted epigenome-wide association analyses, including data from 255 mother-child pairs within the INMA project, and performed a follow-up functional analysis to help the interpretation of the findings. After multiple-testing correction, we found that methylation at 4 CpGs (cg1548200, cg02986379, cg00866476, and cg14113931) was significantly associated with the general cognitive score, and 2 distinct differentially methylated regions (DMRs) (including 27 CpGs) were significantly associated with each cognitive dimension. Interestingly, the genes annotated to these CpGs, such as DAB2, CEP76, PSMG2, or MECOM, are involved in placenta, fetal, and brain development. Moreover, functional enrichment analyses of suggestive CpGs (p < 1 × 10-4) revealed gene sets involved in placenta development, fetus formation, and brain growth. These findings suggest that placental DNA methylation could be a mechanism contributing to the alteration of important pathways in the placenta that have a consequence on the offspring's brain development and cognitive function.

Assuntos

Cognição , Metilação de DNA , Epigênese Genética , Placenta , Humanos , Feminino , Gravidez , Placenta/metabolismo , Pré-Escolar , Masculino , Adulto , Estudo de Associação Genômica Ampla , Ilhas de CpG/genética , Efeitos Tardios da Exposição Pré-Natal/genética

RESUMO

Objective: To investigate the impact of exosomes and microRNA (miRNA) from placental mesenchymal stem cells on chemotherapy-damaged ovarian granulosa cells. Methods: Various public databases were searched for miRNA targeting phosphatase and tensin homologue deleted on chromosome 10 (PTEN) gene. After miRNA transfection into human ovarian granulosa cells, cell growth and expressions of the target miRNA and PTEN were detected. Cisplatin was utilized to induce damage to human ovarian granulosa cells, which were subsequently co-cultured with human placental mesenchymal stem cells and exosomes generated from mesenchymal stem cells, then apoptosis and expressions of PTEN and the target miRNA were detected. Results: After analyzing several databases, miRNA 139-5p (miR-139-5p) was chosen as the target miRNA for this research. Transfection of miR-139-5p mimics into human ovarian granulosa cells elevated miR-139-5p expression level (9 882.080±1 049.130), reduced PTEN protein expression level (0.78±0.11), and increased cell proliferation absorbance (0.85±0.07). Cisplatin treatment severely damaged human ovarian granulosa cells and increased apoptosis, cisplatin-treated cells had a higher apoptosis ratio compared to untreated cells [ (41.9±1.0)% vs (5.0±0.3)%, P<0.001]. In damaged human ovarian granulosa cells, co-cultured with human placental mesenchymal stem cells and exosomes increased miR-139-5p expression levels (1.31±0.04 and 1.20±0.03, respectively) and decreased apoptosis ratios [(20.0±0.4)% and (22.3±1.1)%, respectively]. Conclusion: Placental mesenchymal stem cell-derived exosomes repair damages of cisplatin-induced ovarian granulosa cell and could target PTEN gene through miR-139-5p, which might be a potential option for the treatment of chemotherapy-induced ovarian dysfunction.

Assuntos

Apoptose , Proliferação de Células , Cisplatino , Exossomos , Células da Granulosa , Células-Tronco Mesenquimais , MicroRNAs , PTEN Fosfo-Hidrolase , Placenta , Feminino , MicroRNAs/genética , MicroRNAs/metabolismo , Humanos , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Exossomos/metabolismo , Exossomos/genética , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Células da Granulosa/metabolismo , Cisplatino/efeitos adversos , Placenta/metabolismo , Gravidez , Transfecção , Técnicas de Cocultura , Ovário , Antineoplásicos/efeitos adversos

RESUMO

Coffee is one of the most popular beverages worldwide, and there is an increasing concern of the health risk of coffee consumption in pregnancy. Preeclampsia (PE) is a serious pregnancy disease that causes elevated blood pressure and proteinuria in pregnant women and growth restriction of fetuses due to poorly developed placental vasculature. The aim of our study is to investigate the possible effect of coffee intake during pregnancy in rats with potential underlying vasculature conditions. The endothelial nitric oxide synthase inhibitor N(gamma)-nitro-L-arginine methyl ester (L-NAME) at a high dose (125 mg/kg/d) was used to induce PE in pregnant rats, which were used as the positive control group. In addition, low-dose L-NAME (10 mg/kg/d) was used to simulate the compromised placental vasculature function in pregnant rats. Coffee was given together with low-dose L-NAME to the pregnant rats from gestational day 10.5-18.5. Our results show that the pregnant rats treated with low-dose L-NAME + coffee, but not low-dose L-NAME alone, developed PE symptoms such as prominent fetal growth restriction, hypertension, and proteinuria. Therefore, our findings suggest that coffee intake during pregnancy may cause an increased risk of PE in susceptible women.

Assuntos

Café , NG-Nitroarginina Metil Éster , Pré-Eclâmpsia , Proteinúria , Animais , Gravidez , Feminino , NG-Nitroarginina Metil Éster/farmacologia , Ratos , Retardo do Crescimento Fetal , Pressão Sanguínea , Placenta , Ratos Sprague-Dawley , Inibidores Enzimáticos/farmacologia , Hipertensão , Óxido Nítrico Sintase Tipo III/metabolismo , Modelos Animais de Doenças

Assuntos

Imageamento por Ressonância Magnética , Placenta Acreta , Humanos , Feminino , Placenta Acreta/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Gravidez , Reprodutibilidade dos Testes , Adulto , Estudos Retrospectivos , Placenta/diagnóstico por imagem , Placenta/patologia

RESUMO

BACKGROUND: Imprinted genes play important functions in placentation and pregnancy; however, research on their roles in different placental diseases is limited. It is believed that epigenetic alterations, such as DNA methylation, of placental imprinting genes may contribute to the different pathological features of severe placental diseases, such as pre-eclampsia (PE) and placenta accreta spectrum disorders (PAS). RESULTS: In this study, we conducted a comparative analysis of the methylation and expression of placental imprinted genes between PE and PAS using bisulfite sequencing polymerase chain reaction (PCR) and quantitative PCR, respectively. Additionally, we assessed oxidative damage of placental DNA by determining 8-hydroxy-2'-deoxyguanosine levels and fetal growth by determining insulin-like growth factor 2 (IGF2) and cortisol levels in the umbilical cord blood using enzyme-linked immunosorbent assay. Our results indicated that methylation and expression of potassium voltage-gated channel subfamily Q member 1, GNAS complex locus, mesoderm specific transcript, and IGF2 were significantly altered in both PE and PAS placentas. Additionally, our results revealed that the maternal imprinted genes were significantly over-expressed in PE and significantly under-expressed in PAS compared with a normal pregnancy. Moreover, DNA oxidative damage was elevated and positively correlated with IGF2 DNA methylation in both PE and PAS placentas, and cortisol and IGF2 levels were significantly decreased in PE and PAS. CONCLUSIONS: This study suggested that DNA methylation and expression of imprinted genes are aberrant in both PE and PAS placentas and that PE and PAS have different methylation profiles, which may be linked to their unique pathogenesis.

Assuntos

Metilação de DNA , Impressão Genômica , Fator de Crescimento Insulin-Like II , Pré-Eclâmpsia , Humanos , Feminino , Gravidez , Metilação de DNA/genética , Impressão Genômica/genética , Fator de Crescimento Insulin-Like II/genética , Pré-Eclâmpsia/genética , Adulto , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Placenta/metabolismo , Epigênese Genética/genética , Hidrocortisona/sangue , Doenças Placentárias/genética , Estresse Oxidativo/genética , Sangue Fetal/química , Sangue Fetal/metabolismo , Cromograninas , Proteínas , Canais de Potássio de Abertura Dependente da Tensão da Membrana

RESUMO

PROBLEM: Accelerated placental aging is linked to abnormal fetal growth, preeclampsia (PE), and preterm birth (PTB). NANOG, a transcription factor, is known for its role in cellular reprogramming, self-renewal, and clonogenic growth. Its expression is regulated by Kruppel-like factor 4 (KLF4), which functions as both a transcriptional activator and repressor. This study evaluated the KLF4-NANOG pathway in placental samples from normal pregnancies (NP) as well as those with PE, fetal growth restriction (FGR), and PTB. METHOD OF STUDY: Placental samples from NP pregnancies and those with PE, FGR, and PTB were analyzed for NANOG and KLF4 expression using western blotting and immunohistochemistry. RESULTS: NANOG protein expression was significantly increased in placentas from PE, FGR, and PTB compared to NP (fold changes vs. NP: PE 2.48 ± 0.3, p = 0.002; FGR 1.64 ± 0.16, p = 0.03; PTB 6.03 ± 3.35, p = 0.01). Similarly, KLF4 protein expression was elevated in PE, FGR, and PTB placentas compared to NP (fold changes vs. NP: PE 5.78 ± 0.73, p = 0.001; FGR 2.61 ± 0.43, p = 0.02; PTB 11.42 ± 2.76, p = 0.0006). Immunohistochemistry revealed strong NANOG staining in the syncytiotrophoblast tissue of PE, FGR, and PTB samples, especially in extravillous trophoblasts, compared to NP placentas. CONCLUSIONS: The elevated expression of NANOG and KLF4 in abnormal placental tissues suggests their potential role as markers of enhanced placental aging and dysfunction. These findings underscore the importance of the KLF4-NANOG pathway in the pathology of PE, FGR, and PTB, providing a basis for future research into therapeutic targets for these conditions.

Assuntos

Retardo do Crescimento Fetal , Fator 4 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like , Proteína Homeobox Nanog , Placenta , Pré-Eclâmpsia , Humanos , Feminino , Gravidez , Placenta/metabolismo , Proteína Homeobox Nanog/metabolismo , Proteína Homeobox Nanog/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Adulto , Retardo do Crescimento Fetal/metabolismo , Pré-Eclâmpsia/metabolismo , Nascimento Prematuro/metabolismo , Trofoblastos/metabolismo , Envelhecimento/metabolismo

RESUMO

Proper fetal development requires tight regulation of serotonin concentrations within the fetoplacental unit. This homeostasis is partly maintained by the placental transporter OCT3/SLC22A3, which takes up serotonin from the fetal circulation. Metformin, an antidiabetic drug commonly used to treat gestational diabetes mellitus, was shown to inhibit OCT3. We, therefore, hypothesized that its use during pregnancy could disrupt placental serotonin homeostasis. This hypothesis was tested using three experimental model systems: primary trophoblast cells isolated from the human term placenta, fresh villous human term placenta fragments, and rat term placenta perfusions. Inhibition of serotonin transport by metformin at three concentrations (1 µM, 10 µM, and 100 µM) was assessed in all three models. The OCT3 inhibitor decynium-22 (100 µM) and paroxetine (100 µM), a dual inhibitor of SERT and OCT3, were used as controls. In primary trophoblasts, paroxetine exhibited the strongest inhibition of serotonin uptake, followed by decynium-22. Metformin showed a concentration-dependent effect, reducing serotonin uptake by up to 57 % at the highest concentration. Its inhibitory effect was less pronounced in fresh villous fragments but remained statistically significant at all concentrations. In the perfused rat placenta, metformin demonstrated a concentration-dependent effect, reducing placental serotonin uptake by 44 % at the highest concentration tested. Our findings across all experimental models show inhibition of placental OCT3 by metformin, resulting in reduced serotonin uptake by the trophoblast. This sheds light on mechanisms that may underpin metformin-mediated effects on fetal development.

Assuntos

Metformina , Placenta , Serotonina , Trofoblastos , Metformina/farmacologia , Feminino , Gravidez , Animais , Serotonina/metabolismo , Placenta/metabolismo , Placenta/efeitos dos fármacos , Humanos , Trofoblastos/metabolismo , Trofoblastos/efeitos dos fármacos , Ratos , Transporte Biológico/efeitos dos fármacos , Fator 3 de Transcrição de Octâmero/metabolismo , Hipoglicemiantes/farmacologia , Células Cultivadas , Ratos Wistar , Proteínas de Transporte de Cátions Orgânicos

RESUMO

Congenital Chagas disease (CCD) is a worldwide neglected problem with significant treatment limitations. This study aimed to evaluate the potential of Copaifera spp. oleoresins (ORs) against Trypanosoma cruzi infection in trophoblast cells (BeWo lineage) and human chorionic villous explants (HCVE). The cytotoxicity of ORs was investigated using LDH and MTT assays. T. cruzi (Y strain) proliferation, invasion and reversibility were assessed in OR-treated BeWo cells, and proliferation was evaluated in OR-treated HCVE. The ultrastructure of T. cruzi trypomastigotes and amastigotes treated with ORs were analyzed by scanning and transmission electronic microscopy. ROS production in infected and treated BeWo cells and cytokines in BeWo and HCVE were measured. The ORs irreversibly decreased T. cruzi invasion, proliferation and release in BeWo cells by up to 70 %, 82 % and 80 %, respectively, and reduced parasite load in HCVE by up to 80 %. Significant structural changes in treated parasites were observed. ORs showed antioxidant capacity in BeWo cells, reducing ROS production induced by T. cruzi infection. Also, T. cruzi infection modulated the cytokine profile in both BeWo cells and HCVE; however, treatment with ORs upregulated cytokines decreased by T. cruzi infection in BeWo cells, while downregulated cytokines increased by the T. cruzi infection in HCVE. In conclusion, non-cytotoxic concentrations of Copaifera ORs demonstrated promising potential for controlling T. cruzi infection in models of the human maternal-fetal interface.

Assuntos

Doença de Chagas , Fabaceae , Placenta , Extratos Vegetais , Trofoblastos , Trypanosoma cruzi , Humanos , Trofoblastos/parasitologia , Trofoblastos/efeitos dos fármacos , Trofoblastos/metabolismo , Trypanosoma cruzi/efeitos dos fármacos , Feminino , Extratos Vegetais/farmacologia , Doença de Chagas/parasitologia , Doença de Chagas/tratamento farmacológico , Gravidez , Placenta/parasitologia , Placenta/efeitos dos fármacos , Placenta/metabolismo , Fabaceae/química , Espécies Reativas de Oxigênio/metabolismo , Citocinas/metabolismo , Linhagem Celular

RESUMO

Maternal stress experienced during prenatal development is recognized as a significant risk factor for neurodevelopmental and neuropsychiatric disorders across the offspring's lifespan. The placental barrier serves a crucial function in safeguarding the fetus from detrimental exposures during gestation. However, previous investigations have not yet comprehensively elucidated the extensive connections between prenatal stress and the expression of placental proteins. In this study, we used iTRAQ-based quantitative proteomics to elucidate the placental adaptive mechanisms of pregnant rats in response to fear-induced stress. Our results showed that during pregnancy, exposure to fear-induced stress led to a pathological hypercoagulable state in the mother's body. Placental circulation was also disrupted, significantly reducing placental efficiency and blood oxygen saturation in newborn rats. Proteomic analyses showed that most of the DEPs were annotated to the PI3K-Akt and ECM-receptor interaction signaling pathway. In addition, the expressions of CDC37, HSP90ß, AKT, p-AKT and p-mTOR were down-regulated significantly in the placenta. Our results demonstrated that prenatal fear-induced stress led to inhibition of the cellular signal transduction of placental PI3K/AKT/mTOR, which affected biological processes such as rRNA processing, translation, protein folding, protein stability, and oxygen transport in the placenta. These abnormalities in biological functions could potentially damage the barrier function of the placenta and thereby result in abnormal development in the offspring.

Assuntos

Placenta , Proteômica , Gravidez , Animais , Feminino , Proteômica/métodos , Placenta/metabolismo , Ratos , Fosfatidilinositol 3-Quinases/metabolismo , Estresse Psicológico/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Proteoma/metabolismo

RESUMO

Oropouche virus (OROV) is an emerging arbovirus endemic in Latin America and the Caribbean that causes Oropouche fever, a febrile illness that clinically resembles some other arboviral infections. It is currently spreading through Brazil and surrounding countries, where, from 1 January to 1 August 2024, more than 8000 cases have been identified in Bolivia, Brazil, Columbia, and Peru and for the first time in Cuba. Travelers with Oropouche fever have been identified in the United States and Europe. A significant occurrence during this epidemic has been the report of pregnant women infected with OROV who have had miscarriages and stillborn fetuses with placental, umbilical blood and fetal somatic organ samples that were RT-PCR positive for OROV and negative for other arboviruses. In addition, there have been four cases of newborn infants having microcephaly, in which the cerebrospinal fluid tested positive for IgM antibodies to OROV and negative for other arboviruses. This communication examines the biology, epidemiology, and clinical features of OROV, summarizes the 2023-2024 Oropouche virus epidemic, and describes the reported cases of vertical transmission and congenital infection, fetal death, and microcephaly in pregnant women with Oropouche fever, addresses experimental animal infections and potential placental pathology findings of OROV, and reviews other bunyavirus agents that can cause vertical transmission. Recommendations are made for pregnant women travelling to the regions affected by the epidemic.

Assuntos

Infecções por Bunyaviridae , Transmissão Vertical de Doenças Infecciosas , Microcefalia , Orthobunyavirus , Placenta , Complicações Infecciosas na Gravidez , Natimorto , Gravidez , Feminino , Humanos , Microcefalia/virologia , Microcefalia/epidemiologia , Orthobunyavirus/genética , Orthobunyavirus/isolamento & purificação , Complicações Infecciosas na Gravidez/virologia , Complicações Infecciosas na Gravidez/epidemiologia , Placenta/virologia , Infecções por Bunyaviridae/transmissão , Infecções por Bunyaviridae/epidemiologia , Infecções por Bunyaviridae/virologia , Recém-Nascido , Feto/virologia , Animais

RESUMO

INTRODUCTION: An optimal fetal supply of docosahexaenoic acid (DHA) is critical for normal brain development. The relationship between maternal DHA intake and DHA delivery to the fetus is complex and is dependent on placental handling of DHA. Little data exist on placental DHA levels in pregnancies supplemented with the recommended dose of 200 mg/d. Our objective was to determine how prenatal DHA at the recommended 200 mg/d impacts maternal, placental, and fetal DHA status in both normal-weight and high-BMI women compared to women taking no supplements. METHODS: Maternal blood, placenta, and cord blood were collected from 30 healthy pregnant women (BMI 18.9-43.26 kg/m2) giving birth at term. Red blood cells (RBCs) and villous tissue were isolated, and lipids were extracted to determine DHA content by LC-MS/MS. Data were analyzed by supplement group (0 vs. 200 mg/d) and maternal BMI (normal weight or high BMI) using two-way ANOVA. We measured maternal choline levels in maternal and cord plasma samples. RESULTS: Supplementation with 200 mg/d DHA significantly increased (p < 0.05) maternal and cord RBC DHA content only in pregnancies complicated by high BMI. We did not find any impact of choline levels on maternal or cord RBC phospholipids. There were no significant differences in total placental DHA content by supplementation or maternal BMI (p > 0.05). Placental levels of phosphatidylinositol (PI) and phosphatidic acid containing DHA species were higher (p < 0.05) in high-BMI women without DHA supplementation compared to both normal-BMI and high-BMI women taking DHA supplements. CONCLUSION: Maternal DHA supplementation at recommended doses cord increased RBC DHA content only in pregnancies complicated by higher BMI. Surprisingly, we found that obesity was related to an increase in placental PI and phosphatidic acid species, which was ameliorated by DHA supplementation. Phosphatidic acid activates placental mTOR, which regulates amino acid transport and may explain previous findings of the impact of DHA on placental function. Current recommendations for DHA supplementation may not be achieving the goal of improving fetal DHA levels in normal-weight women.

Assuntos

Índice de Massa Corporal , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos , Sangue Fetal , Fosfolipídeos , Placenta , Humanos , Feminino , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Docosa-Hexaenoicos/sangue , Gravidez , Placenta/metabolismo , Adulto , Fosfolipídeos/sangue , Sangue Fetal/química , Sangue Fetal/metabolismo , Eritrócitos/metabolismo , Adulto Jovem , Complicações na Gravidez , Feto/metabolismo , Colina/administração & dosagem , Colina/sangue , Fenômenos Fisiológicos da Nutrição Materna

RESUMO

Nutritional intake during pregnancy can affect gestational length, fetal development, and impact postnatal growth and health in offspring. Perturbations in maternal nutrition with either an excess or deficiency in nutrients during pregnancy may have harmful effects on the offspring's development and increase the risk of developing chronic diseases later in life. In pregnancy, nutrients transfer from the mother to the fetus via the placenta. Essential fatty acids, linoleic acid (LA) and alpha linoleic acid (ALA), can only be obtained in the diet. In Western countries, the ratio of LA and ALA in the diet has increased dramatically in recent decades. Some animal and human studies have found a correlation between maternal intake of LA and birth weight; however, the association varies. In contrast, some human studies have demonstrated inconclusive findings regarding the correlation between cord blood levels of LA and birth outcomes. In addition, high dietary LA intake in animal studies in pregnancy increased the production of inflammatory markers such as prostaglandins, leukotrienes, cytokines, and tumour necrosis factor-alpha. This review aims to highlight the effect of high dietary LA intake during pregnancy on birth outcomes, obesity, maternal inflammatory markers, and the transfer of fatty acids across the placenta.

Assuntos

Ácido Linoleico , Fenômenos Fisiológicos da Nutrição Materna , Gravidez , Humanos , Feminino , Ácido Linoleico/administração & dosagem , Placenta/metabolismo , Animais , Dieta , Peso ao Nascer , Resultado da Gravidez , Recém-Nascido , Troca Materno-Fetal

RESUMO

The well-known cotinine test captures recent smoking, and survey responses are not always accurate. Now researchers propose a measure of DNA methylation in placental tissue that may be better than either.

Assuntos

Biomarcadores , Metilação de DNA , Epigênese Genética , Humanos , Feminino , Gravidez , Biomarcadores/análise , Placenta/metabolismo , Cotinina/análise , Poluição por Fumaça de Tabaco , Exposição Materna/estatística & dados numéricos , Fumar

RESUMO

Background and Objectives: The study aims to explore the potential for transplacental transmission of SARS-CoV-2, focusing on its pathophysiology, placental defense mechanisms, and the clinical implications for maternal and neonatal health. Materials and Methods: A comprehensive review of the current literature was conducted, analyzing studies on SARS-CoV-2 infection in pregnancy, the expression of key viral receptors (ACE2 and TMPRSS2) in placental cells, and the immune responses involved in placental defense. The review also examined the clinical outcomes related to maternal and neonatal health, including adverse pregnancy outcomes and neonatal infection. Results: The expression of ACE2 and TMPRSS2 in the placenta supports the biological plausibility of SARS-CoV-2 transplacental transmission. Histopathological findings from the infected placentas reveal inflammation, vascular changes, and the evidence of viral particles in placental tissues. Clinical reports indicate an increased risk of preterm birth, intrauterine growth restriction, and neonatal infection in pregnancies affected by COVID-19. However, the frequency and mechanisms of vertical transmission remain variable across studies, highlighting the need for standardized research protocols. Conclusions: SARS-CoV-2 can potentially infect placental cells, leading to adverse pregnancy outcomes and neonatal infection. While evidence of transplacental transmission has been documented, the risk and mechanisms are not fully understood. Ongoing research is essential to clarify these aspects and inform obstetric care practices to improve maternal and neonatal outcomes during the COVID-19 pandemic.

Assuntos

Enzima de Conversão de Angiotensina 2 , COVID-19 , Transmissão Vertical de Doenças Infecciosas , Placenta , Complicações Infecciosas na Gravidez , SARS-CoV-2 , Humanos , Gravidez , COVID-19/transmissão , Feminino , Complicações Infecciosas na Gravidez/virologia , Placenta/virologia , Enzima de Conversão de Angiotensina 2/metabolismo , Recém-Nascido , Serina Endopeptidases/metabolismo , Resultado da Gravidez

RESUMO

Accidental exposure to high-dose radiation while pregnant has shown significant negative effects on the developing fetus. One fetal organ which has been studied is the placenta. The placenta performs all essential functions for fetal development, including nutrition, respiration, waste excretion, endocrine communication, and immunological functions. Improper placental development can lead to complications during pregnancy, as well as the occurrence of intrauterine growth-restricted (IUGR) offspring. IUGR is one of the leading indicators of fetal programming, classified as an improper uterine environment leading to the predisposition of diseases within the offspring. With numerous studies examining fetal programming, there remains a significant gap in understanding the placenta's role in irradiation-induced fetal programming. This review aims to synthesize current knowledge on how irradiation affects placental function to guide future research directions. This review provides a comprehensive overview of placental biology, including its development, structure, and function, and summarizes the placenta's role in fetal programming, with a focus on the impact of radiation on placental biology. Taken together, this review demonstrates that fetal radiation exposure causes placental degradation and immune function dysregulation. Given the placenta's crucial role in fetal development, understanding its impact on irradiation-induced IUGR is essential.

Assuntos

Desenvolvimento Fetal , Placenta , Exposição à Radiação , Radiação Ionizante , Gravidez , Humanos , Feminino , Placenta/efeitos da radiação , Desenvolvimento Fetal/efeitos da radiação , Exposição à Radiação/efeitos adversos , Animais , Retardo do Crescimento Fetal/etiologia , Feto/efeitos da radiação

RESUMO

Galectins are a class of lectins that are extensively expressed in all organisms. Galectins are involved in a range of functions, including early development, tissue regeneration, cancer and inflammation. It has been shown that galectin-8 is expressed in the villous and extravillous trophoblast (EVT) cells of the human placenta; however, its physiological role in pregnancy establishment has not been elucidated. Taking these factors into account, we investigated the functional role of galectin-8 in HTR-8/SVneo cells-a human EVT cell line-and human primary cytotrophoblast cells isolated from a first-trimester placenta. We analyzed the effects of recombinant human galectin-8 (rh galectin-8) on the adhesion, migration and invasion of HTR-8/SVneo cells. We used qPCR, cell-based ELISA (cELISA) and gelatin zymography to study the effects of galectin-8 on mediators of these processes, such as integrin subunits alpha-1 and beta-1 and matrix metalloproteinases (MMPs)-2 and -9, on the mRNA and protein levels. Further, we studied the effects of galectin-8 on primary cytotrophoblast cells' invasion. Galectin-8 stimulated the adhesion, migration and invasion of HTR-8/SVneo cells, as well as the invasion of primary cytotrophoblasts. In addition, the MMP-2 and -9 levels were increased, while the expression of integrins alpha-1 and beta-1 was not affected. Galectin-8 has the ability to positively affect EVTs' invasion, so it can be considered a significant factor in the trophoblast cell invasion process.

Assuntos

Adesão Celular , Movimento Celular , Galectinas , Metaloproteinase 2 da Matriz , Trofoblastos , Humanos , Trofoblastos/metabolismo , Trofoblastos/citologia , Galectinas/metabolismo , Movimento Celular/efeitos dos fármacos , Gravidez , Feminino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 2 da Matriz/genética , Linhagem Celular , Metaloproteinase 9 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Placenta/metabolismo , Placenta/citologia , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/metabolismo

RESUMO

Gestational diabetes mellitus (GDM) is a common condition during pregnancy. The prevalence of GDM is continuously increasing worldwide. Due to accessible diagnostic methods and a clear understanding of risk factors, GDM can be effectively diagnosed and managed. Galectins may influence immunomodulatory and inflammatory processes. This study examines the expression of galectin-7 in the placentas of women with gestational diabetes (GDM), compares it to its expression in healthy pregnancies, and evaluates the associated clinical outcomes. The placentas of 40 healthy women and 40 GDM placentas were included in the cohort. The expression level of galecin-7 was measured in the syncytiotrophoblast (SCT) and in the decidua of the placenta by immunohistochemistry and double immunofluorescence staining. The evaluation was performed by an immunoreactivity score (IRS). The study results show an increased expression of galectin-7 in the SCT and the decidua of GDM placentas as compared to the placentas of the control group. Elevated levels of galectin-7 were observed in both the nucleus and the cytoplasm. This study investigated the hypothesis that galectins are involved in pathophysiological processes of gestational diabetes. Statistical analysis of gene expression patterns confirmed that galectin-7 is indeed upregulated in GDM placentas. Further studies are needed to show the correlation of galectin-7 and the development and maintenance of gestational diabetes mellitus.

Assuntos

Diabetes Gestacional , Galectinas , Placenta , Humanos , Diabetes Gestacional/metabolismo , Diabetes Gestacional/genética , Feminino , Gravidez , Galectinas/metabolismo , Galectinas/genética , Placenta/metabolismo , Adulto , Trofoblastos/metabolismo , Decídua/metabolismo , Decídua/patologia , Estudos de Casos e Controles