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1.
Nat Neurosci ; 24(10): 1392-1401, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34400844

RESUMO

Compromised placental function or premature loss has been linked to diverse neurodevelopmental disorders. Here we show that placenta allopregnanolone (ALLO), a progesterone-derived GABA-A receptor (GABAAR) modulator, reduction alters neurodevelopment in a sex-linked manner. A new conditional mouse model, in which the gene encoding ALLO's synthetic enzyme (akr1c14) is specifically deleted in trophoblasts, directly demonstrated that placental ALLO insufficiency led to cerebellar white matter abnormalities that correlated with autistic-like behavior only in male offspring. A single injection of ALLO or muscimol, a GABAAR agonist, during late gestation abolished these alterations. Comparison of male and female human preterm infant cerebellum also showed sex-linked myelination marker alteration, suggesting similarities between mouse placental ALLO insufficiency and human preterm brain development. This study reveals a new role for a placental hormone in shaping brain regions and behaviors in a sex-linked manner. Placental hormone replacement might offer novel therapeutic opportunities to prevent later neurobehavioral disorders.


Assuntos
Cerebelo/crescimento & desenvolvimento , Glândulas Endócrinas/fisiologia , Placenta/fisiologia , Pregnanolona/deficiência , Pregnanolona/fisiologia , Comportamento Social , Aldeído Redutase/genética , Animais , Transtorno do Espectro Autista/etiologia , Cerebelo/fisiologia , Feminino , Agonistas GABAérgicos/farmacologia , Moduladores GABAérgicos , Deleção de Genes , Humanos , Lactente , Recém-Nascido , Masculino , Camundongos , Muscimol/farmacologia , Gravidez , Receptores de GABA-A/fisiologia , Caracteres Sexuais , Trofoblastos/metabolismo , Substância Branca/patologia
2.
Int J Mol Sci ; 22(12)2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34203717

RESUMO

It is well understood that sex differences exist between females and males even before they are born. These sex-dependent differences may contribute to altered growth and developmental outcomes for the fetus. Based on our initial observations in the human placenta, we hypothesised that the male prioritises growth pathways in order to maximise growth through to adulthood, thereby ensuring the greatest chance of reproductive success. However, this male-specific "evolutionary advantage" likely contributes to males being less adaptable to shifts in the in-utero environment, which then places them at a greater risk for intrauterine morbidities or mortality. Comparatively, females are more adaptable to changes in the in-utero environment at the cost of growth, which may reduce their risk of poor perinatal outcomes. The mechanisms that drive these sex-specific adaptations to a change in the in-utero environment remain unclear, but an increasing body of evidence within the field of developmental biology would suggest that alterations to placental function, as well as the feto-placental hormonal milieu, is an important contributing factor. Herein, we have addressed the current knowledge regarding sex-specific intrauterine growth differences and have examined how certain pregnancy complications may alter these female- and male-specific adaptations.


Assuntos
Desenvolvimento Embrionário , Desenvolvimento Fetal/fisiologia , Placenta/fisiologia , Caracteres Sexuais , Androgênios/metabolismo , Animais , Feminino , Glucocorticoides/metabolismo , Humanos , Masculino , Gravidez
3.
Int J Mol Sci ; 22(14)2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34298913

RESUMO

Up to 11% of pregnancies extend to post-term with adverse obstetric events linked to pregnancies over 42 weeks. Oxidative stress and senescence (cells stop growing and dividing by irreversibly arresting their cell cycle and gradually ageing) can result in diminished cell function. There are no detailed studies of placental cell senescence markers across a range of gestational ages, although increased levels have been linked to pre-eclampsia before full term. This study aimed to determine placental senescence and oxidative markers across a range of gestational ages in women with uncomplicated pregnancies and those with a diagnosis of pre-eclampsia. Placentae were obtained from 37 women with uncomplicated pregnancies of 37-42 weeks and from 13 cases of pre-eclampsia of 31+2-41+2 weeks. The expression of markers of senescence, oxidative stress, and antioxidant defence (tumour suppressor protein p16INK4a, kinase inhibitor p21, interleukin-6 (IL-6), NADPH oxidase 4 (NOX4), glutathione peroxidases 1, 3, and 4 (GPx1, GPx3, and GPx4), placental growth factor (PlGF), and soluble fms-like tyrosine kinase-1 (sFlt-1)) genes was measured (quantitative real-time PCR). Protein abundance of p16INK4a, IL-6, NOX4, 8-hydroxy-2'-deoxy-guanosine (8-OHdG), and PlGF was assessed by immunocytochemistry. Placental NOX4 protein was higher in post-term than term deliveries and further increased by pre-eclampsia (p < 0.05 for all). P21 expression was higher in post-term placentae (p = 0.012) and in pre-eclampsia (p = 0.04), compared to term. Placental P16INK4a protein expression was increased post-term, compared to term (p = 0.01). In normotensive women, gestational age at delivery was negatively associated with GPx4 and PlGF (mRNA and protein) (p < 0.05 for all), whereas a positive correlation was seen with placental P21, NOX4, and P16INK4a (p < 0.05 for all) expression. Markers of placental oxidative stress and senescence appear to increase as gestational age increases, with antioxidant defences diminishing concomitantly. These observations increase our understanding of placental health and may contribute to assessment of the optimal gestational age for delivery.


Assuntos
Senescência Celular/fisiologia , Estresse Oxidativo/fisiologia , Placenta/fisiologia , Pré-Eclâmpsia/fisiopatologia , Adulto , Biomarcadores/metabolismo , Feminino , Idade Gestacional , Humanos , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Gravidez , Resultado da Gravidez , RNA Mensageiro/metabolismo
4.
J Nutr Biochem ; 96: 108784, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34062269

RESUMO

The maternal n-3 polyunsaturated fatty acid (PUFA) deficiency on decidual vascular structure and angiogenesis in mice placenta was investigated. Namely, we studied uterine artery remodeling, fatty acid metabolism, and placental epigenetic methylation in this animal model. Weanling female Swiss albino mice were fed either alpha-linolenic acid (18:3 n-3, ALA) deficient diets (0.13% energy from ALA) or a sufficient diet (2.26% energy from ALA) throughout the study. The dietary n-3 PUFA deficiency altered uteroplacental morphology and vasculature by reversing luminal to vessel area and increased luminal wall thickness at 8.5-12.5gD. Further, placentas (F0 and F1) showed a significant decrease in the expression of VCAM1, HLAG proteins and an increase in MMP9, KDR expression. The conversion of ALA to long-chain (LC) n-3 PUFAs was significantly decreased in plasma and placenta during the n-3 deficiency state. Reduced n-3 LCPUFAs increased the placental expression of intracellular proteins FABP3, FABP4, and ADRP to compensate decreased availability of these fatty acids in the n-3 deficient mice. The N-3 PUFA deficiency significantly increased the 5-methylcytosine levels in the placenta but not in the liver. The alteration in DNA methylation continued to the next generation in the placental epigenome with augmented expression of DNMT3A and DNMT3B. Our study showed that maternal n-3 PUFA deficiency alters placental vascular architecture and induces epigenetic changes suggesting the importance of n-3 PUFA intake during the development of the fetus. Moreover, the study shows that the placenta is the susceptible target for epigenetic alteration in maternal deficiency n-3 fatty acids.


Assuntos
Epigenoma , Ácidos Graxos Ômega-3/metabolismo , Placenta/irrigação sanguínea , Artéria Uterina/ultraestrutura , Animais , Metilação de DNA , Dieta , Feminino , Fenômenos Fisiológicos da Nutrição Materna , Camundongos , Placenta/fisiologia , Gravidez , Artéria Uterina/fisiologia
6.
Int J Mol Sci ; 22(10)2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-34069909

RESUMO

The application of mesenchymal stromal cells (MSCs) from different sources, including bone marrow (BM, bmMSCs), adipose tissue (atMSCs), and human term placenta (hPSCs) has been proposed for various clinical purposes. Accumulated evidence suggests that the activity of the different MSCs is indirect and associated with paracrine release of pro-regenerative and anti-inflammatory factors. A major limitation of bmMSCs-based treatment for autologous application is the limited yield of cells harvested from BM and the invasiveness of the procedure. Similar effects of autologous and allogeneic MSCs isolated from various other tissues were reported. The easily available fresh human placenta seems to represent a preferred source for harvesting abundant numbers of human hPSCs for allogenic use. Cells derived from the neonate tissues of the placenta (f-hPSC) can undergo extended expansion with a low risk of senescence. The low expression of HLA class I and II on f-hPSCs reduces the risk of rejection in allogeneic or xenogeneic applications in normal immunocompetent hosts. The main advantage of hPSCs-based therapies seems to lie in the secretion of a wide range of pro-regenerative and anti-inflammatory factors. This renders hPSCs as a very competent cell for therapy in humans or animal models. This review summarizes the therapeutic potential of allogeneic applications of f-hPSCs, with reference to their indirect pro-regenerative and anti-inflammatory effects and discusses clinical feasibility studies.


Assuntos
Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/metabolismo , Placenta/metabolismo , Tecido Adiposo/metabolismo , Aloenxertos/metabolismo , Animais , Medula Óssea/metabolismo , Células da Medula Óssea/metabolismo , Diferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Terapia Baseada em Transplante de Células e Tecidos/métodos , Feminino , Humanos , Placenta/fisiologia , Gravidez , Células Estromais/metabolismo
7.
Genes (Basel) ; 12(5)2021 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-34068942

RESUMO

Phylogenetic trees based on multiple genomic loci enable us to estimate the evolution of functional constraints that operate on genes based on lineage-specific fluctuation of the evolutionary rate at particular gene loci, "gene-branch interactions". Using this information as predictors, our previous work inferred that the common ancestor of placental mammals was nocturnal, insectivorous, solitary, and bred seasonally. Here, we added seven new continuous traits including lifespan, bodyweight, and five reproduction-related traits and inferred the coevolution network of 14 core life history traits for 89 mammals. In this network, bodyweight and lifespan are not directly connected to each other; instead, their correlation is due to both of them coevolving with gestation period. Diurnal mammals are more likely to be monogamous than nocturnal mammals, while arboreal mammals tend to have a smaller litter size than terrestrial mammals. Coevolution between diet and the seasonal breeding behavior test shows that year-round breeding preceded the dietary change to omnivory, while seasonal breeding preceded the dietary change to carnivory. We also discuss the evolution of reproductive strategy of mammals. Genes selected as predictors were identified as well; for example, genes function as tumor suppressor were selected as predictors of weaning age.


Assuntos
Mamíferos/genética , Mamíferos/fisiologia , Reprodução/genética , Reprodução/fisiologia , Animais , Peso Corporal/genética , Peso Corporal/fisiologia , Feminino , Genoma/genética , Tamanho da Ninhada de Vivíparos/genética , Tamanho da Ninhada de Vivíparos/fisiologia , Longevidade/genética , Longevidade/fisiologia , Filogenia , Placenta/fisiologia , Gravidez
8.
Commun Biol ; 4(1): 749, 2021 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-34140619

RESUMO

The uterus is the organ for embryo implantation and fetal development. Most current models of the uterus are centred around capturing its function during later stages of pregnancy to increase the survival in pre-term births. However, in vitro models focusing on the uterine tissue itself would allow modelling of pathologies including endometriosis and uterine cancers, and open new avenues to investigate embryo implantation and human development. Motivated by these key questions, we discuss how stem cell-based uteri may be engineered from constituent cell parts, either as advanced self-organising cultures, or by controlled assembly through microfluidic and print-based technologies.


Assuntos
Células-Tronco/fisiologia , Engenharia Tecidual/métodos , Útero/citologia , Útero/fisiologia , Animais , Implantação do Embrião/fisiologia , Feminino , Desenvolvimento Fetal/fisiologia , Humanos , Modelos Biológicos , Placenta/fisiologia , Gravidez , Primatas , Tecidos Suporte
9.
PLoS One ; 16(5): e0248980, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34043633

RESUMO

AIM: Growth differentiation factor 15 (GDF15) increases in serum during pregnancy to levels not seen in any other physiological state and is suggested to be involved in pregnancy-induced nausea, weight regulation and glucose metabolism. The main action of GDF15 is regulated through a receptor of the brainstem, i.e., through exposure of GDF15 in both blood and cerebrospinal fluid (CSF). The aim of the current study was to measure GDF15 in both CSF and serum during pregnancy, and to compare it longitudinally to non-pregnant levels. METHODS: Women were sampled at elective caesarean section (n = 45, BMI = 28.1±5.0) and were followed up 5 years after pregnancy (n = 25). GDF15, insulin and leptin were measured in CSF and serum. Additional measurements included plasma glucose, and serum adiponectin and Hs-CRP. RESULTS: GDF15 levels were higher during pregnancy compared with follow-up in both CSF (385±128 vs. 115±32 ng/l, P<0.001) and serum (73789±29198 vs. 404±102 ng/l, P<0.001). CSF levels correlated with serum levels during pregnancy (P<0.001), but not in the non-pregnant state (P = 0.98). Both CSF and serum GDF15 were highest in women carrying a female fetus (P<0.001). Serum GDF15 correlated with the homeostatic model assessment for beta-cell function and placental weight, and CSF GDF15 correlated inversely with CSF insulin levels. CONCLUSION: This, the first study to measure CSF GDF15 during pregnancy, demonstrated increased GDF15 levels in both serum and CSF during pregnancy. The results suggest that effects of GDF15 during pregnancy can be mediated by increases in both CSF and serum levels.


Assuntos
Fator 15 de Diferenciação de Crescimento/sangue , Adiponectina/sangue , Adulto , Glicemia/análise , Proteína C-Reativa/análise , Cesárea , Feminino , Seguimentos , Fator 15 de Diferenciação de Crescimento/líquido cefalorraquidiano , Humanos , Insulina/sangue , Leptina/sangue , Placenta/fisiologia , Gravidez
10.
Biochem Biophys Res Commun ; 559: 70-77, 2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-33933992

RESUMO

CULLIN1 (CUL1) protein, as a scaffold protein in Skp1-CUL1-F box (SCF) E3 ligases complex, was reported involved in different cellular functions to regulate the early embryonic development. In our previous study, we have demonstrated that CUL1 promote trophoblast cell invasion at the maternal-fetal interface in human and the CUL1 protein significantly decreased in preeclampsia (PE) placenta, but how CUL1 involved in placentation is still obscure. Due to the embryo lethal in CUL1 knockout mice, the lentivirus mediated placenta-specific CUL1 knockdown mice model was constructed to uncover the potential role of CUL1 in placentation. In this study, CUL1 was first detected in mouse placenta. CUL1 mainly expressed in trophoblast giant cell at E9.5, and spongiotrophoblast at E11.5 and E13.5 by using immunohistochemistry and int situ hybridization. In lentivirus mediated placenta specific mouse model, the number of implanted embryos was reduced in CUL1 shRNA group at E13.5 and E18.5 compared to control group. Based on the morphological analysis of histologic staining, we observed that spongiotrophoblast layer is expanded, fetal angiogenesis in labyrinth was obstructed and fetus blood cells were accumulated in vessels. These results indicated that decreased expression of CUL1 affect placentation of mice, which give new insights into the cause of gestational diseases, but the exactly mechanism still needs further study.


Assuntos
Proteínas Culina/metabolismo , Placentação , Animais , Linhagem Celular , Proteínas Culina/análise , Proteínas Culina/genética , Implantação do Embrião , Feminino , Camundongos , Camundongos Knockout , Placenta/patologia , Placenta/fisiologia , Gravidez , Trofoblastos/metabolismo , Trofoblastos/patologia
12.
Reprod Domest Anim ; 56(5): 703-712, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33580900

RESUMO

Adhesion process ensures the formation of the appropriate connection between mother and foetus during placentation and further placental development, which determines physiological pregnancy course. Extracellular matrix of foetal membranes are a rich source of biologically active proteins, the synthesis of which is regulated by hormones. Depending on the stage of pregnancy, the protein profile of the placenta changes, thanks to which its remodelling is possible. The aim of the study was to evaluate the effect of decorin, as well as selected glycosylation inhibitors on the adhesion of caruncular epithelial cells derived from cows during pregnancy. Placental cells were isolated from healthy, pregnant (2nd and 4th month) cows after slaughter, which allowed for the establishment of 4 primary cell cultures without visible cells of fibroblast morphology. The presence of decorin in cell monolayer and cell lysates was determined by the use of immunocytochemistry and Western blotting, respectively. The viability of cells was evaluated by MTT assay. The adhesion of cells to fibronectin was measured spectrophotometrically. Protein N-glycosylation and O-glycosylation have a modulating effect on the adhesion and viability of placental cells during early-mid pregnancy. Decorin and tunicamycin were shown to have anti-adhesive properties with respect to caruncular cells of the pregnant bovine uterus.


Assuntos
Decorina/farmacologia , Glicosilação/efeitos dos fármacos , Placenta/fisiologia , Animais , Bovinos , Adesão Celular/efeitos dos fármacos , Sobrevivência Celular , Células Cultivadas , Células Epiteliais , Feminino , Fibronectinas/metabolismo , Placentação/fisiologia , Gravidez , Tunicamicina/farmacologia
13.
Oxid Med Cell Longev ; 2021: 8839394, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33542786

RESUMO

1-O-Hexyl-2,3,5-trimethylhydroquinone (HTHQ), a potent nuclear factor-E2-related factor 2 (Nrf2) activator, has potent antioxidant activity by scavenging reactive oxygen species (ROS). However, the role of HTHQ on the development of preeclampsia (PE) and the underlying mechanisms have barely been explored. In the present study, PE model was induced by adenovirus-mediated overexpression of soluble fms-like tyrosine kinase 1 (sFlt-1) in pregnant mice. The results showed that HTHQ treatment significantly relieved the high systolic blood pressure (SBP) and proteinuria and increased the fetal weight and fetal weight/placenta weight in preeclamptic mice. Furthermore, we found that HTHQ treatment significantly decreased soluble endoglin (sEng), endothelin-1 (ET-1), and activin A and restored vascular endothelial growth factor (VEGF) in preeclamptic mice. In addition, HTHQ treatment inhibited oxidative stress and endothelial cell apoptosis by increasing the levels of Nrf2 and its downstream haemoxygenase-1 (HO-1) protein. In line with the data in vivo, we discovered that HTHQ treatment attenuated oxidative stress and cell apoptosis in human umbilical vein endothelial cells (HUVECs) following hypoxia and reperfusion (H/R), and the HTHQ-mediated protection was lost after transfected with siNrf2. In conclusion, these results suggested that HTHQ ameliorates the development of preeclampsia through suppression of oxidative stress and endothelial cell apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Hidroquinonas/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Pré-Eclâmpsia/prevenção & controle , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Células Cultivadas , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/fisiologia , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Hidroquinonas/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Placenta/efeitos dos fármacos , Placenta/fisiologia , Pré-Eclâmpsia/metabolismo , Pré-Eclâmpsia/fisiopatologia , Gravidez
14.
J Assist Reprod Genet ; 38(4): 865-871, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33534049

RESUMO

PURPOSE: To report the rate of fetal anomalies detected on anatomy ultrasound in pregnant patients who underwent IVF with preimplantation genetic testing for aneuploidy (PGT-A) compared to patients who conceived following IVF with unscreened embryos and age-matched patients with natural conceptions. METHODS: Retrospective cohort study at a single maternal-fetal medicine practice. Patients with singleton pregnancies who had a mid-trimester anatomy ultrasound between January 2017 and December 2018 were screened for inclusion. A total of 712 patients who conceived after IVF with or without PGT-A were age-matched with natural conception controls. The primary outcome was the rate of fetal and placental anomalies detected on mid-trimester anatomical survey. Secondary outcomes included the rates of abnormal nuchal translucency (NT), second trimester serum analytes, non-invasive prenatal testing (NIPT), and invasive diagnostic testing. RESULT(S): There were no differences in the rate of fetal anomalies in patients who underwent IVF with PGT-A compared to patients who conceived following IVF with unscreened embryos and age-matched patients with natural conceptions. Rate of abnormal NT, high-risk NIPT, and abnormal invasive diagnostic testing were also similar. Patients who conceived after IVF with or without PGT-A had higher rates of abnormal placental ultrasound findings and abnormal second trimester serum analytes compared to natural conception controls. CONCLUSION: The use of PGT-A was not associated with a difference in risk of fetal anomaly detection on a mid-trimester anatomical survey. The results of this study highlight the importance of improved patient counseling regarding the limitations of PGT-A, and of providing standard prenatal care for pregnancies conceived through ART, regardless of whether PGT-A was performed.


Assuntos
Aneuploidia , Transferência Embrionária , Fertilização In Vitro , Diagnóstico Pré-Implantação , Adulto , Técnicas de Imagem por Elasticidade , Feminino , Fertilização , Humanos , Placenta/fisiologia , Gravidez
15.
Clin Ther ; 43(2): 287-296, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33483135

RESUMO

The racial disparity associated with preterm birth is a public health concern in the United States. The placenta is the principal metabolic, respiratory, and endocrine organ of the fetus and a key route by which environmental exposures are transmitted from mother to offspring. Available at every delivery, it may serve as a marker of differences in prenatal exposures that manifest differently by race. Recently, we described differences in placental pathology between African-American and White preterm births: the prevalence of chronic inflammation was higher among African-American women's placentas compared with those of White women. Similarly, racial differences have been shown in placental malperfusion and placental weight. Social determinants such as poverty and stress from discrimination have been implicated in racial disparities in preterm birth. To date, however, the underlying biological mechanisms, whether through inflammatory, oxidative stress, or other pathways involving epigenetic programming, remain largely unknown. The placenta, complemented by maternal and umbilical cord blood biomarkers, may provide important information on the perinatal environment that explains the origins of racial disparities in preterm birth rates and subsequent health outcomes. This article reviews existing literature and current research gaps. Opportunities are discussed for future placental research that may reveal novel mechanisms leading to the development of new approaches in the prevention and management of preterm birth and its outcomes.


Assuntos
Afro-Americanos , Biomarcadores/sangue , Saúde Materna/etnologia , Placenta/fisiologia , Nascimento Prematuro/etnologia , Adulto , Epigenômica , Grupo com Ancestrais do Continente Europeu , Feminino , Humanos , Recém-Nascido , Placenta/patologia , Placenta/fisiopatologia , Gravidez , Nascimento Prematuro/fisiopatologia , Determinantes Sociais da Saúde , Estados Unidos
16.
Mol Biol Rep ; 48(2): 1291-1297, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33507474

RESUMO

Physiological balance between pro- and antioxidative processes is crucial for placentation and further development of fetus and placenta. Parameters of pro- and antioxidative profile may serve as markers of proper course of pregnancy. The aim of study was to assess whether the balance between pro- and antioxidative parameters during placentation phase in bovine placenta is maintained. Placental and blood samples were collected from healthy, HF, pregnant (2nd-3rd month) cows (n = 8) in slaughterhouse and in farm, respectively. Formylokinurenine and bityrosine content were measured spectrofluorimetrically in blood plasma and tissue homogenates while metabolites of lipid peroxidation, total antioxidant capacity, SH groups and activity of antioxidative enzymes (glutathione peroxidase and superoxide dismutase) were determined in examined tissues by spectrophotometry. Western blotting was used to confirm the presence of enzymatic proteins in placenta. Results: Local profile in tissues was more pronounced than general profile in blood plasma. Activities of antioxidative enzymes were significantly (p < 0.05) higher in 2nd compared to 3rd month of pregnancy in maternal part of placenta while prooxidant parameters showed opposite relationship. Obtained results showed significant differences when compared to data from non-pregnant animals or time of parturition. Further studies are necessary for elucidation of placentation phase in cows.


Assuntos
Antioxidantes/metabolismo , Oxidantes/metabolismo , Placenta/metabolismo , Placentação/genética , Animais , Bovinos , Feminino , Feto , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Peroxidação de Lipídeos/genética , Placenta/fisiologia , Gravidez , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo
17.
Clin Ther ; 43(2): 246-264, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33446335

RESUMO

In recent decades, our understanding of the disrupted mechanisms that contribute to major obstetrical diseases, including preeclampsia, fetal growth restriction, preterm birth, and gestational diabetes, has increased exponentially. Common to many of these obstetric diseases is placental maldevelopment and dysfunction; the placenta is a significant component of the maternal-fetal interface involved in coordinating, facilitating, and regulating maternal and fetal nutrient, oxygen and waste exchange, and hormone and cytokine production. Despite the advances in our understanding of placental development and function, there are currently no treatments for placental maldevelopment and dysfunction. However, given the transient nature and accessibility from the maternal circulation, the placenta offers a unique opportunity to develop targeted therapeutics for routine obstetric practices. Furthermore, given the similar developmental paradigms between the placenta and cancer, there is an opportunity to appropriate current knowledge from advances in targeted therapeutics in cancer treatments. In this review, we highlight the similarities between early placental development and cancer and introduce a number of targeted therapies currently being explored in cancer and pregnancy. We also propose a number of new effectors currently being targeted in cancer research that have the potential to be targeted in the development of treatments for pregnancy complications. Finally, we describe a method for targeting the placenta using nonviral polymers that are capable of delivering plasmids, small interfering RNA, and other effector nucleic acids, which could ultimately improve fetal and maternal outcomes from complicated pregnancies.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Neoplasias/terapia , Placenta/fisiopatologia , Complicações na Gravidez/terapia , Fator A de Crescimento do Endotélio Vascular/uso terapêutico , Animais , Modelos Animais de Doenças , Portadores de Fármacos , Feminino , Retardo do Crescimento Fetal/fisiopatologia , Humanos , Camundongos , Neoplasias/fisiopatologia , Placenta/fisiologia , Polímeros , Pré-Eclâmpsia/fisiopatologia , Gravidez , Nascimento Prematuro
18.
Med Sci Sports Exerc ; 53(4): 756-762, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32991347

RESUMO

INTRODUCTION: Adherence to physical activity (PA) and gestational weight gain (GWG) recommendations during pregnancy has been shown to improve maternal and fetal health outcomes, including reducing the risk for chronic diseases. Limited research has evaluated the effect of meeting PA in combination with GWG recommendations on placental efficiency (Pl-E), a surrogate marker of the placenta's ability to exchange nutrients and gas based on surface area. The purpose of this study was to measure and compare Pl-E based on meeting PA and GWG recommendations. METHOD: Healthy pregnant women (n = 61) wore accelerometers in their second and third trimesters to objectively measure PA. Women were classified as active or inactive at each time point based on meeting the 2019 Canadian prenatal PA guidelines. Total GWG was calculated as weight measured in the third trimester minus self-reported prepregnancy weight, and were categorized as insufficient (n = 19), adequate (n = 22), and excessive (n = 20) according to the 2009 Institute of Medicine guidelines. Placental weight (PW) and birth weight (BW) were measured within 30 min of delivery and 24-48 h postdelivery, respectively. Pl-E was determined in three ways: BW:PW ratio, residual BW, and measured BW, with a higher value indicating better Pl-E. Pl-E was compared by PA and GWG status using a two-way ANOVA. RESULTS: No differences were found in the BW:PW ratio or residual BW corresponding to PA and GWG status. Measured BW was significantly higher in newborns of women who gained weight excessively compared with those who gained insufficient weight (P < 0.05). CONCLUSION: These findings suggest that prenatal PA does not compromise Pl-E; however, further research is required to evaluate the potential mechanistic benefits of meeting PA and GWG guidelines on the placenta.


Assuntos
Exercício Físico/fisiologia , Ganho de Peso na Gestação/fisiologia , Troca Materno-Fetal/fisiologia , Placenta/fisiologia , Acelerometria/instrumentação , Adulto , Análise de Variância , Peso ao Nascer , Feminino , Guias como Assunto , Humanos , Tamanho do Órgão , Placenta/anatomia & histologia , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Adulto Jovem
19.
Placenta ; 103: 141-151, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33126048

RESUMO

BACKGROUND: Though a large number of pregnant females have been affected by COVID-19, there is a dearth of information on the effects of SARS-CoV-2 infection on trophoblast function. We explored in silico, the potential interactions between SARS-CoV-2 proteins and proteins involved in the key functions of placenta. METHODS: Human proteins interacting with SARS-CoV-2 proteins were identified by Gordon et al. (2020). Genes that are upregulated in trophoblast sub-types and stages were obtained by gene-expression data from NCBI-GEO and by text-mining. Genes altered in pathological states like pre-eclampsia and gestational diabetes mellitus were also identified. Genes crucial in placental functions thus identified were compared to the SARS-CoV-2 interactome for overlaps. Proteins recurring across multiple study scenarios were analyzed using text mining and network analysis for their biological functions. RESULTS: The entry receptors for SARS-CoV-2 - ACE2 and TMPRSS2 are expressed in placenta. Other proteins that interact with SARS-CoV-2 like LOX, Fibulins-2 and 5, NUP98, GDF15, RBX1, CUL3, HMOX1, PLAT, MFGE8, and MRPs are vital in placental functions like trophoblast invasion and migration, syncytium formation, differentiation, and implantation. TLE3, expressed across first trimester placental tissues and cell lines, is involved in formation of placental vasculature, and is important in SARS-CoV (2003) budding and exit from the cells by COPI vesicles. CONCLUSION: SARS-CoV-2 can potentially interact with proteins having crucial roles in the placental function. Whether these potential interactions identified in silico have effects on trophoblast functions in biological settings needs to be addressed by further in vitro and clinical studies.


Assuntos
Biologia Computacional , Proteínas da Gravidez/metabolismo , Mapas de Interação de Proteínas , SARS-CoV-2/metabolismo , Trofoblastos/fisiologia , COVID-19/metabolismo , COVID-19/patologia , Simulação por Computador , Conjuntos de Dados como Assunto , Feminino , Células HEK293 , Humanos , Placenta/metabolismo , Placenta/fisiologia , Placenta/virologia , Gravidez , Complicações Infecciosas na Gravidez/metabolismo , Complicações Infecciosas na Gravidez/patologia , Primeiro Trimestre da Gravidez/metabolismo , Ligação Proteica , Proteômica/métodos , Trofoblastos/metabolismo , Trofoblastos/virologia , Regulação para Cima
20.
Clin Ther ; 43(2): 226-245, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33358257

RESUMO

PURPOSE: Maternal nutrition is a key modifier of fetal growth and development. However, many maternal diets in the United States do not meet nutritional recommendations. Dietary supplementation is therefore necessary to meet nutritional goals. The effects of many supplements on placental development and function are poorly understood. In this review, we address the therapeutic potential of maternal dietary supplementation on placental development and function in both healthy and complicated pregnancies. METHODS: This is a narrative review of original research articles published between February 1970 and July 2020 on dietary supplements consumed during pregnancy and placental outcomes (including nutrient uptake, metabolism and delivery, as well as growth and efficiency). Impacts of placental changes on fetal outcomes were also reviewed. Both human and animal studies were included. FINDINGS: We found evidence of a potential therapeutic benefit of several supplements on maternal and fetal outcomes via their placental impacts. Our review supports a role for probiotics as a placental therapeutic, with effects that include improved inflammation and lipid metabolism, which may prevent preterm birth and poor placental efficiency. Supplementation with omega-3 fatty acids (as found in fish oil) during pregnancy tempers the negative effects of maternal obesity but may have little placental impact in healthy lean women. The beneficial effects of choline supplementation on maternal health and fetal growth are largely attributable to its placental impacts. l-arginine supplementation has a potent provascularization effect on the placenta, which may underlie its fetal growth-promoting properties. IMPLICATIONS: The placenta is exquisitely sensitive to dietary supplements. Pregnant women should consult their health care practitioner before continuing or initiating use of a dietary supplement. Because little is known about impacts of many supplements on placental and long-term offspring health, more research is required before robust clinical recommendations can be made.


Assuntos
Suplementos Nutricionais , Desenvolvimento Fetal/efeitos dos fármacos , Micronutrientes/uso terapêutico , Placenta/efeitos dos fármacos , Animais , Arginina/farmacologia , Arginina/uso terapêutico , Feminino , Humanos , Fenômenos Fisiológicos da Nutrição Materna , Micronutrientes/farmacologia , Placenta/fisiologia , Gravidez , Complicações na Gravidez , Nascimento Prematuro/prevenção & controle , Cuidado Pré-Natal
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