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1.
Sheng Li Xue Bao ; 72(1): 115-124, 2020 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-32099989

RESUMO

Placenta serves as a temporary fetal organ, which mediates maternal-fetal crosstalk and intrauterine fetal growth. Placental defensive barrier is a fundamental physiological function, which balances maternal immune tolerance to the fetus and resistance to pathogens. This review summarizes the latest research progress on the mechanisms of placental barrier formation from the view of placental development. Recent discoveries have shed light on the cellular and molecular properties of placental defensive mechanisms in syncytiotrophoblast, including autophagy, exosome mediated anti-pathogenic pathways, cell-cell junctions and cytoskeleton networks. We also present an overview of placental barrier dysfunction and its implications in intrauterine TORCH infections.


Assuntos
Troca Materno-Fetal , Placenta/fisiologia , Trofoblastos/fisiologia , Autofagia , Citoesqueleto , Exossomos , Feminino , Desenvolvimento Fetal , Feto , Humanos , Gravidez
2.
Cell Mol Life Sci ; 77(2): 253-265, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31468060

RESUMO

Dysregulation of angiogenesis is a phenomenon observed in several disorders such as diabetic foot, critical limb ischemia and myocardial infarction. Mesenchymal stromal cells (MSCs) possess angiogenic potential and have recently emerged as a powerful tool for cell therapy to promote angiogenesis. Although bone marrow-derived MSCs are the primary cell of choice, obtaining them has become a challenge. The placenta has become a popular alternative as it is a highly vascular organ, easily available and ethically more favorable with a rich supply of MSCs. Comparatively, placenta-derived MSCs (PMSCs) are clinically promising due to their proliferative, migratory, clonogenic and immunomodulatory properties. PMSCs release a plethora of cytokines and chemokines key to angiogenic signaling and facilitate the possibility of delivering PMSC-derived exosomes as a targeted therapy to promote angiogenesis. However, there still remains the challenge of heterogeneity in the isolated populations, questions on the maternal or fetal origin of these cells and the diversity in previously reported isolation and culture conditions. Nonetheless, the growing rate of clinical trials using PMSCs clearly indicates a shift in favor of PMSCs. The overall aim of the review is to highlight the importance of this rather poorly understood cell type and emphasize the need for further investigations into their angiogenic potential as an alternative source for therapeutic angiogenesis.


Assuntos
Células-Tronco Mesenquimais/fisiologia , Neovascularização Fisiológica/fisiologia , Placenta/fisiologia , Animais , Exossomos/fisiologia , Feminino , Humanos , Gravidez
3.
Environ Health Perspect ; 127(11): 117001, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31691586

RESUMO

BACKGROUND: Although studies have provided estimates of premature mortality to either heat or cold in adult populations, and fetal exposure to ambient temperature may be associated with life expectancy, the effects of temperature on aging in early life have not yet been studied. Telomere length (TL) is a marker of biological aging, and a short TL at birth may predict lifespan and disease susceptibility later in life. OBJECTIVES: We studied to what extent prenatal ambient temperature exposure is associated with newborn TL. METHODS: In the ENVIRONAGE (ENVIRonmental influence ON early AGEing) birth cohort in Flanders, Belgium, we measured cord blood and placental TL in 1,103 mother-newborn pairs (singletons with ≥36wk of gestation) using a quantitative real-time polymerase chain reaction (qPCR) method. We associated newborn TL with average weekly exposure to ambient temperature using distributed lag nonlinear models (DLNMs) while controlling for potential confounders. Double-threshold DLNMs were used to estimate cold and heat thresholds and the linear associations between temperature and TL below the cold threshold and above the heat threshold. RESULTS: Prenatal temperature exposure above the heat threshold (19.5°C) was associated with shorter cord blood TL. The association with a 1°C increase in temperature was strongest at week 36 of gestation and resulted in a 3.29% [95% confidence interval (CI): -4.67, -1.88] shorter cord blood TL. Consistently, prenatal temperature exposure below the cold threshold (5.0°C) was associated with longer cord blood TL. The association with a 1°C decrease in temperature was strongest at week 10 of gestation with 0.72% (95% CI: 0.46, 0.97) longer cord blood TL. DISCUSSION: Our study supports potential effects of prenatal temperature exposure on longevity and disease susceptibility later in life. Future climate scenarios might jeopardize the potential molecular longevity of future generations from birth onward. https://doi.org/10.1289/EHP5153.


Assuntos
Envelhecimento/fisiologia , Temperatura Baixa , Sangue Fetal/fisiologia , Temperatura Alta , Exposição Materna , Placenta/fisiologia , Encurtamento do Telômero/fisiologia , Adulto , Bélgica , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Longevidade , Masculino , Gravidez , Adulto Jovem
4.
PLoS Genet ; 15(8): e1008236, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31369552

RESUMO

The placenta is the interface between maternal and fetal circulations, integrating maternal and fetal signals to selectively regulate nutrient, gas, and waste exchange, as well as secrete hormones. In turn, the placenta helps create the in utero environment and control fetal growth and development. The unique epigenetic profile of the human placenta likely reflects its early developmental separation from the fetus proper and its role in mediating maternal-fetal exchange that leaves it open to a range of exogenous exposures in the maternal circulation. In this review, we cover recent advances in DNA methylation in the context of placental function and development, as well as the interaction between the pregnancy and the environment.


Assuntos
Exposição Ambiental/efeitos adversos , Troca Materno-Fetal/genética , Placenta/fisiologia , Placentação/genética , Metilação de DNA/fisiologia , Epigênese Genética/fisiologia , Feminino , Hormônios/metabolismo , Humanos , Exposição Materna/efeitos adversos , Placenta/citologia , Gravidez , Resultado da Gravidez , Análise de Célula Única
5.
Reprod Biol Endocrinol ; 17(1): 65, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399145

RESUMO

Kisspeptin and its G protein-coupled receptor KISS1R play key roles in mammalian reproduction due to their involvement in the onset of puberty and control of the hypothalamic-pituitary-gonadal axis. However, recent studies have indicated a potential role of extra-hypothalamic kisspeptin in reproductive function. Here, we summarize recent advances in our understanding of the physiological significance of kisspeptin/KISS1R in the peripheral reproductive system (including the ovary, testis, uterus, and placenta) and the potential role of kisspeptin/KISS1R in reproductive diseases. A comprehensive understanding of the expression, function, and potential molecular mechanisms of kisspeptin/KISS1R in the peripheral reproductive system will contribute to the diagnosis, treatment and prevention of reproductive diseases.


Assuntos
Kisspeptinas/fisiologia , Receptores de Kisspeptina-1/fisiologia , Animais , Feminino , Kisspeptinas/genética , Kisspeptinas/metabolismo , Masculino , Oócitos/crescimento & desenvolvimento , Ovário/crescimento & desenvolvimento , Ovário/metabolismo , Ovulação , Placenta/metabolismo , Placenta/fisiologia , Gravidez , Receptores de Kisspeptina-1/genética , Receptores de Kisspeptina-1/metabolismo , Espermatogênese , Testículo/metabolismo , Útero/metabolismo
6.
Orv Hetil ; 160(32): 1247-1259, 2019 Aug.
Artigo em Húngaro | MEDLINE | ID: mdl-31387374

RESUMO

The aim of this review is to explore, in addition to revealing the biological background, new conceptual and therapeutic approaches for reproductive clinicians to provide better and more effective care for sterile and infertile couples. In humans, 75% of unsuccessful pregnancies are the result of failures of implantation, and implantation failure is the limiting factor for in vitro fertilization treatment. A modified "good" inflammation is necessary for implantation and parturition, but for most of pregnancy, inflammation threatens the continuation of pregnancy. During this period, maintaining the non-inflammatory condition is extremely important, enabling the maternal epigenetic effects to occur in the fetus, making it possible for the offspring to adapt as much as possible to the extrauterine life. In the maintenance of the non-inflammatory condition of pregnancy, a large amount of progesterone hormone produced by the placenta (after the luteo-placental shift) plays a crucial role. It has been reported that the role of inflammation during implantation is an ancestral response to the embryo as a foreign body. During normal pregnancy, this inflammation is initiated by the trophoblast and involves the suppression of neutrophil infiltration, the recruitment of natural killer cells to the site of implantation as well as the production of a range of proinflammatory cytokines. During the "implantation window", the uterus is primed to produce several inflammatory signals such as prostaglandin E2 and a range of proinflammatory cytokines, including TNF, IL6 and IFNγ. The feto-placental unit is a semi-foreign graft called a "semi allograft", and the recognition of pregnancy by the mother (host) and the resulting maternal immune tolerance is an essential part of successful pregnancy and the birth of a healthy fetus. Because of the functional or absolute reduction of circulating progesterone (due to the decreasing hormone production of the physiologically "aging" placenta after around the 36th week of pregnancy) progesterone effects become insufficient. Therefore it is unable to suppress the production of IL8 and other inflammatory cytokines and the term inflammation, leading to cervical ripening, uterus contractions and parturition ("good" inflammation). Orv Hetil. 2019; 160(32): 1247-1259.


Assuntos
Parto/fisiologia , Placenta/fisiologia , Manutenção da Gravidez/imunologia , Progesterona/fisiologia , Feminino , Feto , Humanos , Parto/imunologia , Placenta/imunologia , Gravidez , Manutenção da Gravidez/fisiologia , Trofoblastos
7.
Environ Pollut ; 254(Pt A): 112991, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31421572

RESUMO

Cadmium (Cd), a ubiquitous environmental pollutant, is known to impair placental development. However, the underlying mechanisms remain unclear. The present study used in vivo and in vitro models to investigate the effects of Cd on apoptosis and autophagy in placental trophoblasts and its mechanism. Pregnant mice were exposed to CdCl2 (4.5 mg/kg) on gestational day (GD) 9. Human JEG-3 cells were exposed to CdCl2 (0-40 µM) for different time points. Gestational Cd exposure obviously lowered the weight and diameter of mouse placentas. Number of TUNEL-positive cells was markedly elevated in Cd-administered mouse placentas and JEG-3 cells. Correspondingly, Cd significantly up-regulated cleaved caspase-3 protein level, a key indicator of apoptosis, in murine placentas and JEG-3 cells. Simultaneously, Cd also triggered autophagy, as determined by an elevation of LC3B-II and p62 protein, and accumulation of LC3-positive puncta, in placental trophoblasts. Chloroquine an autophagy inhibitor, obviously aggravated Cd-induced apoptosis in JEG-3 cells. By contrast, rapamycin, a specific autophagy inducer, significantly alleviated Cd-triggered apoptosis in JEG-3 cells. Mechanistically, autophagy inhibited Cd-induced apoptosis mainly via degrading caspase-9. Co-localizations of p62, a classical autophagic receptor, and caspase-9 were observed in Cd-stimulated human JEG-3 cells. Moreover, p62 siRNAs pretreatment markedly blocked the degradation of caspase 9 proteins via Cd-activated autophagy in JEG-3 cells. Collectively, our data suggest that activation of autophagy inhibits Cd-induced apoptosis via p62-mediated caspase-9 degradation in placental trophoblasts. These findings provide a new mechanistic insight into Cd-induced impairments of placental and fetal development.


Assuntos
Autofagia/fisiologia , Cádmio/toxicidade , Substâncias Perigosas/toxicidade , Placenta/fisiologia , Trofoblastos/fisiologia , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Cádmio/metabolismo , Caspase 3 , Caspase 9 , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Placenta/metabolismo , Gravidez , Testes de Toxicidade , Trofoblastos/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
8.
Endocrinology ; 160(9): 2189-2203, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31294776

RESUMO

Defective placental implantation and vascularization with accompanying hypoxia contribute to preeclampsia (PE), a leading cause of maternal and neonatal morbidity and mortality. Genetic and epigenetic mechanisms underlying differentiation of proliferative cytotrophoblasts (CytTs) to multinucleated syncytiotrophoblast (SynT) are incompletely defined. The SynT performs key functions in nutrient and gas exchange, hormone production, and protection of the fetus from rejection by the maternal immune system. In this study, we used chromatin immunoprecipitation sequencing of midgestation human trophoblasts before CytT and after SynT differentiation in primary culture to analyze changes in binding of RNA polymerase II (Pol II) and of active and repressive histone marks during SynT differentiation. Our findings reveal that increased Pol II binding to promoters of a subset of genes during trophoblast differentiation was closely correlated with active histone marks. This gene set was enriched in those controlling immune response and immune modulation, including interferon-induced tetratricopeptide repeat and placenta-specific glycoprotein gene family members. By contrast, genes downregulated during SynT differentiation included proinflammatory transcription factors ERG1, cFOS, and cJUN, as well as members of the NR4A orphan nuclear receptor subfamily, NUR77, NURR1, and NOR1. Downregulation of proinflammatory transcription factors upon SynT differentiation was associated with decreased promoter enrichment of endogenous H3K27Ac and H3K9Ac and enhanced binding of H3K9me3 and histone deacetylase 1. However, promoter enrichment of H3K27me3 was low in both CytT and SynT and was not altered with changes in gene expression. These findings provide important insight into mechanisms underlying human trophoblast differentiation and may identify therapeutic targets for placental disorders, such as PE.


Assuntos
Epigênese Genética , Regulação da Expressão Gênica , Trofoblastos/citologia , Diferenciação Celular , Fusão Celular , Células Cultivadas , Feminino , Histonas/metabolismo , Humanos , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/genética , Placenta/fisiologia , Gravidez , Regiões Promotoras Genéticas , RNA Polimerase II/metabolismo , Trofoblastos/metabolismo
9.
BMC Evol Biol ; 19(1): 156, 2019 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-31349784

RESUMO

BACKGROUND: The evolution of complex organs is thought to occur via a stepwise process, each subsequent step increasing the organ's complexity by a tiny amount. This evolutionary process can be studied by comparing closely related species that vary in the presence or absence of their organs. This is the case for the placenta in the live-bearing fish family Poeciliidae, as members of this family vary markedly in their ability to supply nutrients to their offspring via a placenta. Here, we investigate the genomic basis underlying this phenotypic variation in Heterandria formosa, a poeciliid fish with a highly complex placenta. We compare this genome to three published reference genomes of non-placental poeciliid fish to gain insight in which genes may have played a role in the evolution of the placenta in the Poeciliidae. RESULTS: We sequenced the genome of H. formosa, providing the first whole genome sequence for a placental poeciliid. We looked for signatures of adaptive evolution by comparing its gene sequences to those of three non-placental live-bearing relatives. Using comparative evolutionary analyses, we found 17 genes that were positively selected exclusively in H. formosa, as well as five gene duplications exclusive to H. formosa. Eight of the genes evolving under positive selection in H. formosa have a placental function in mammals, most notably endometrial tissue remodelling or endometrial cell proliferation. CONCLUSIONS: Our results show that a substantial portion of positively selected genes have a function that correlates well with the morphological changes that form the placenta of H. formosa, compared to the corresponding tissue in non-placental poeciliids. These functions are mainly endometrial tissue remodelling and endometrial cell proliferation. Therefore, we hypothesize that natural selection acting on genes involved in these functions plays a key role in the evolution of the placenta in H. formosa.


Assuntos
Evolução Biológica , Sequência Conservada , Ciprinodontiformes/genética , Genoma , Placenta/fisiologia , Animais , Feminino , Duplicação Gênica , Gravidez , Seleção Genética , Sequenciamento Completo do Genoma
10.
Nat Commun ; 10(1): 3335, 2019 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-31350395

RESUMO

In live-bearing animal lineages, the evolution of the placenta is predicted to create an arena for genomic conflict during pregnancy, drive patterns of male sexual selection, and increase the rate of speciation. Here we test these predictions of the viviparity driven conflict hypothesis (VDCH) in live-bearing poecilid fishes, a group showing multiple independent origins of placentation and extreme variation in male sexually selected traits. As predicted, male sexually selected traits are only gained in lineages that lack placentas; while there is little or no influence of male traits on the evolution of placentas. Both results are consistent with the mode of female provisioning governing the evolution of male attributes. Moreover, it is the presence of male sexually selected traits (pre-copulatory), rather than placentation (post-copulatory), that are associated with higher rates of speciation. These results highlight a causal interaction between female reproductive mode, male sexual selection and the rate of speciation, suggesting a role for conflict in shaping diverse aspects of organismal biology.


Assuntos
Evolução Biológica , Peixes/genética , Animais , Tamanho Corporal , Feminino , Peixes/classificação , Peixes/crescimento & desenvolvimento , Peixes/fisiologia , Masculino , Filogenia , Placenta/fisiologia , Placentação , Gravidez , Reprodução
11.
Nat Rev Nephrol ; 15(11): 693-712, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31164719

RESUMO

The (pro)renin receptor ((P)RR) was first identified as a single-transmembrane receptor in human kidneys and initially attracted attention owing to its potential role as a regulator of the tissue renin-angiotensin system (RAS). Subsequent studies found that the (P)RR is widely distributed in organs throughout the body, including the kidneys, heart, brain, eyes, placenta and the immune system, and has multifaceted functions in vivo. The (P)RR has roles in various physiological processes, such as the cell cycle, autophagy, acid-base balance, energy metabolism, embryonic development, T cell homeostasis, water balance, blood pressure regulation, cardiac remodelling and maintenance of podocyte structure. These roles of the (P)RR are mediated by its effects on important biological systems and pathways including the tissue RAS, vacuolar H+-ATPase, Wnt, partitioning defective homologue (Par) and tyrosine phosphorylation. In addition, the (P)RR has been reported to contribute to the pathogenesis of diseases such as fibrosis, hypertension, pre-eclampsia, diabetic microangiopathy, acute kidney injury, cardiovascular disease, cancer and obesity. Current evidence suggests that the (P)RR has key roles in the normal development and maintenance of vital organs and that dysfunction of the (P)RR is associated with diseases that are characterized by a disruption of the homeostasis of physiological functions.


Assuntos
Receptores de Superfície Celular/fisiologia , ATPases Vacuolares Próton-Translocadoras/fisiologia , Encéfalo/fisiologia , Encéfalo/fisiopatologia , Olho/fisiopatologia , Feminino , Coração/fisiologia , Coração/fisiopatologia , Homeostase/fisiologia , Humanos , Sistema Imunitário/fisiologia , Sistema Imunitário/fisiopatologia , Rim/fisiologia , Rim/fisiopatologia , Fenômenos Fisiológicos Oculares , Placenta/fisiologia , Placenta/fisiopatologia , Gravidez , Sistema Renina-Angiotensina/fisiologia
12.
Bioessays ; 41(6): e1800232, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31119755

RESUMO

A new interpretation of human menstruation is presented, resulting from a cross-disciplinary investigation of evolution, developmental biology, and physiology. A process evolutionarily associated with childbirth expresses itself as menstruation in women for whom frequent and continual failure to conceive has become the default situation. In humans and Old World primates, contractile uterine spiral arterioles evolved as the complement of the highly invasive hemochorionic placenta and is the selected phenotype. Placental progesterone withdrawal during the last stage of birth leads to arrested blood flow through maternal spiral arterioles, allowing detachment of the deciduous placenta with minimal maternal hemorrhage. In nonpregnant females, progesterone withdrawal from a degenerating corpus luteum initiates menstruation and stops blood flow through uterine spiral arterioles. Both events share similar physiological mechanisms and sequences. This explanation may improve our understanding of a recurrent event experienced by half of the human population and for a quarter of their adult reproductive life.


Assuntos
Menstruação/fisiologia , Parto/fisiologia , Placenta/fisiologia , Progesterona/metabolismo , Adulto , Animais , Arteríolas/fisiologia , Encéfalo/embriologia , Feminino , Feto , Humanos , Gravidez , Reprodução/fisiologia , Útero/irrigação sanguínea
13.
J Clin Lab Anal ; 33(6): e22918, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31131498

RESUMO

BACKGROUNDS: One of the limitations of somatic cell nuclear transfer (SCNT) strategy to generate genetically modified offspring is the low birth rate. Placental dysfunction is one of the causes of abortion. Circular RNA (circRNA) is noncoding RNA which functions as microRNA (miRNA) sponges in biological processes. METHODS: Two aberrant pregnant placenta (aberrant group, AG) and three normal pregnant placenta (normal group, NG) during late gestation (180-210 days) with bovine SCNT fetus were collected for high-throughput sequencing and analyzed. The host genes of differentially expressed (DE) circRNAs were predicted. And the microRNAs (miRNAs) which could interact with DE circRNAs were analyzed. Then, the expressional level of partial DE circRNAs and corresponding host genes was verified through qRT-PCR. At last, the function of host genes was analyzed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). RESULTS: Altogether 123 differentially expressed circRNAs between two groups were identified, which were found related to 60 host genes and 32 miRNAs. The top 10 upregulated circRNAs were bta_circ_0012985, bta_circ_0013071, bta_circ_0013074, bta_circ_0016024, bta_circ_0013068, bta_circ_0008816, bta_circ_0012982, bta_circ_0013072, bta_circ_0019285, and bta_circ_0013067. The top 10 downregulated circRNAs were bta_circ_0024234, bta_circ_0017528, bta_circ_0008077, bta_circ_0003222, bta_circ_0007500, bta_circ_0020328, bta_circ_0011001, bta_circ_0016364, bta_circ_0008839, and bta_circ_0016049. The qRT-PCR results showed consistent trend with sequencing analysis result, while host genes had no statistic difference. The GO and KEGG analyses of the host genes suggested that abnormal circRNA expression may play multiple roles in placental structure and dysfunction. CONCLUSION: The abnormal circRNA expression may be one of reasons of placental dysfunction, leads to abortion of bovine SCNT fetus.


Assuntos
Técnicas de Transferência Nuclear , Placenta/fisiologia , /genética , Animais , Bovinos , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Ontologia Genética , Idade Gestacional , MicroRNAs/genética , Placenta/fisiopatologia , Gravidez , Reprodutibilidade dos Testes
14.
J Korean Med Sci ; 34(16): e128, 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31020816

RESUMO

BACKGROUND: Little research based on the artificial neural network (ANN) is done on preterm birth (spontaneous preterm labor and birth) and its major determinants. This study uses an ANN for analyzing preterm birth and its major determinants. METHODS: Data came from Anam Hospital in Seoul, Korea, with 596 obstetric patients during March 27, 2014 - August 21, 2018. Six machine learning methods were applied and compared for the prediction of preterm birth. Variable importance, the effect of a variable on model performance, was used for identifying major determinants of preterm birth. Analysis was done in December, 2018. RESULTS: The accuracy of the ANN (0.9115) was similar with those of logistic regression and the random forest (0.9180 and 0.8918, respectively). Based on variable importance from the ANN, major determinants of preterm birth are body mass index (0.0164), hypertension (0.0131) and diabetes mellitus (0.0099) as well as prior cone biopsy (0.0099), prior placenta previa (0.0099), parity (0.0033), cervical length (0.0001), age (0.0001), prior preterm birth (0.0001) and myomas & adenomyosis (0.0001). CONCLUSION: For preventing preterm birth, preventive measures for hypertension and diabetes mellitus are required alongside the promotion of cervical-length screening with different guidelines across the scope/type of prior conization.


Assuntos
Nascimento Prematuro , Adulto , Área Sob a Curva , Índice de Massa Corporal , Colo do Útero/fisiologia , Diabetes Mellitus/patologia , Feminino , Idade Gestacional , Humanos , Hipertensão/patologia , Recém-Nascido , Modelos Logísticos , Trabalho de Parto Prematuro , Placenta/fisiologia , Gravidez , Curva ROC , Fatores de Risco
16.
Clin Perinatol ; 46(2): 383-398, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31010566

RESUMO

Pregnancy profoundly alters a woman's physiology. These changes alter drug absorption, distribution, metabolism, and elimination and emphasize the pharmacologic complexity of pregnancy. They also emphasize the dangers of extrapolating pharmacologic expectations from nonpregnant populations to pregnant women and their fetuses. Although concerns about fetal safety have historically limited pharmacokinetic studies during pregnancy, it is important to recognize that many medications are clinically indicated for various maternal or fetal conditions, and it is particularly important that these therapies be evidence-based with appropriate study, including short-term and long-term outcomes data.


Assuntos
Feto/metabolismo , Troca Materno-Fetal , Preparações Farmacêuticas/metabolismo , Placenta/metabolismo , Gravidez/metabolismo , Feminino , Feto/fisiologia , Humanos , Farmacocinética , Placenta/fisiologia , Gravidez/fisiologia
17.
PLoS One ; 14(4): e0214951, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30943260

RESUMO

Exposure to intrauterine inflammation (IUI) is associated with short- and long-term adverse perinatal outcomes. However, little data exist on utilizing placenta to prognosticate fetal injury in this scenario. Our study aimed to utilize imaging modalities to evaluate mechanisms contributing to placental injury following IUI exposure and correlated it to concomitant fetal brain injury. CD1 pregnant dams underwent laparotomies and received intrauterine injections of either lipopolysaccharide (LPS; a model of IUI) or phosphate-buffered saline (PBS). In utero ultrasound Doppler velocimetry of uterine and umbilical arteries and magnetic resonance imaging (MRI) of placental volumes with confirmatory immunohistochemical (vimentin) and histochemistry (fibrin) analyses were performed. ELISA for thrombosis markers, fibrinogen and fibrin was performed to analyze thrombi in placenta. Fetal brain immunohistochemistry was performed to detect microglial activation (ionized calcium-binding adaptor molecule 1, Iba1). On ultrasound, LPS group demonstrated elevated resistance indices, pulsatility indices and a greater occurrence of absent end-diastolic flow in the umbilical and uterine arteries. In the fetus, there was an increased cardiac Tei indices in the LPS group. MRI revealed decreased volume of placenta in the LPS group associated with placental thinning and placental endothelial damage on immunohistochemistry. Decreased fibrinogen content and more thrombi staining in placenta exposed to maternal LPS indicated the hypercoagulability. Furthermore, the expression of Iba1was significantly associated with placental thickness (r = -0.7890, Pearson correlation coefficient). Our data indicate that IUI can trigger events leading to maternal placental malperfusion and fetal vessel resistance, as well as predispose the developing fetus to cardiac dysfunction and brain damage. Furthermore, our data suggest that prenatal ultrasound can be a real-time clinical tool for assessing fetal risk for adverse neurologic outcomes following the potential IUI exposure.


Assuntos
Lesões Encefálicas , Doenças Fetais , Inflamação , Lipopolissacarídeos/toxicidade , Doenças Placentárias , Placenta , Animais , Lesões Encefálicas/induzido quimicamente , Lesões Encefálicas/metabolismo , Lesões Encefálicas/patologia , Feminino , Doenças Fetais/induzido quimicamente , Doenças Fetais/metabolismo , Doenças Fetais/patologia , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Camundongos , Placenta/lesões , Placenta/metabolismo , Placenta/fisiologia , Doenças Placentárias/induzido quimicamente , Doenças Placentárias/metabolismo , Doenças Placentárias/patologia , Gravidez
18.
J Anim Sci ; 97(6): 2555-2568, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-30968113

RESUMO

In vitro embryo production (IVP) in cattle has gained worldwide interest in recent years, but the efficiency of using IVP embryos for calf production is far from optimal. This review will examine the pregnancy retention rates of IVP embryos and explore causes for pregnancy failures. Based on work completed over the past 25 yr, only 27% of cattle receiving IVP embryos will produce a live calf. Approximately 60% of these pregnancies fail during the first 6 wk of gestation. When compared with embryos generated by superovulation, pregnancy rates are 10% to 40% lower for cattle carrying IVP embryos, exemplifying that IVP embryos are consistently less competent than in vivo-generated embryos. Several abnormalities have been observed in the morphology of IVP conceptuses. After transfer, IVP embryos are less likely to undergo conceptus elongation, have reduced embryonic disk diameter, and have compromised yolk sac development. Marginal binucleate cell development, cotyledon development, and placental vascularization have also been documented, and these abnormalities are associated with altered fetal growth trajectories. Additionally, in vitro culture conditions increase the risk of large offspring syndrome. Further work is needed to decipher how the embryo culture environment alters post-transfer embryo development and survival. The risk of these neonatal disorders has been reduced by the use of serum-free synthetic oviductal fluid media formations and culture in low oxygen tension. However, alterations are still evident in IVP oocyte and embryo transcript abundances, timing of embryonic cleavage events and blastulation, incidence of aneuploidy, and embryonic methylation status. The inclusion of oviductal and uterine-derived embryokines in culture media is being examined as one way to improve the competency of IVP embryos. To conclude, the evidence presented herein clearly shows that bovine IVP systems still must be refined to make it an economical technology in cattle production systems. However, the current shortcomings do not negate its current value for certain embryo production needs and for investigating early embryonic development in cattle.


Assuntos
Bovinos/fisiologia , Transferência Embrionária/veterinária , Embrião de Mamíferos/fisiologia , Taxa de Gravidez , Animais , Transferência Embrionária/economia , Desenvolvimento Embrionário , Feminino , Oócitos/fisiologia , Placenta/fisiologia , Gravidez , Útero/fisiologia
19.
Ital J Pediatr ; 45(1): 39, 2019 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-30885231

RESUMO

The term "Lotus Birth" identifies the practice of not cutting the umbilical cord and of leaving the placenta attached to the newborn after its expulsion until it detaches spontaneously, which generally occurs 3-10 days after birth. The first reported cases of Lotus Birth date back to 2004 in Australia.Supporters of such a procedure claim that the newborn is better perfused, endowed with a more robust immune system and "less stressed".However, it should be pointed out that histopathological study of the placenta is increasingly being requested in order to investigate problems of an infective nature or dysmaturity affecting the foetus, and situations of risk affecting the mother. Moreover, from the legal standpoint, there is no uniform position on the question of whether the placenta belongs to the mother or to the newborn. Lastly, a proper conservation of the embryonic adnexa is very difficult and includes problems of a hygiene/health, infectivological and medico-legal nature.The authors analyzed all these aspect in the Italian legislative framework, reaching the conclusion that Lotus Birth is inadvisable from both the scientific and logical/rational points of view.


Assuntos
Bioética , Parto Obstétrico/legislação & jurisprudência , Parto Obstétrico/métodos , Placenta/fisiologia , Cordão Umbilical/fisiologia , Feminino , Humanos , Recém-Nascido , Itália , Masculino , Tratamentos com Preservação do Órgão/métodos , Circulação Placentária/fisiologia , Gravidez , Resultado da Gravidez , Fatores de Tempo
20.
BMC Genomics ; 20(1): 254, 2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30925895

RESUMO

BACKGROUND: Placental efficiency (PE) describes the relationship between placental and fetal weights (fetal wt/placental wt). Within litters, PE can vary drastically, resulting in similarly sized pigs associated with differently sized placentas, up to a 25% weight difference. However, the mechanisms enabling the smaller placenta to grow a comparable littermate are unknown. To elucidate potential mechanisms, morphological measurements and gene expression profiles in placental and associated endometrial tissues of high PE and low PE feto-placental units were compared. Tissue samples were obtained from eight maternal line gilts during gestational day 95 ovario-hysterectomies. RNA was extracted from tissues of feto-placental units with the highest and lowest PE in each litter and sequenced. RESULTS: Morphological measurements, except placental weight, were not different (P > 0.05) between high and low PE. No DEG were identified in the endometrium and 214 DEG were identified in the placenta (FDR < 0.1), of which 48% were upregulated and 52% were downregulated. Gene ontology (GO) analysis revealed that a large percentage of DEG were involved in catalytic activity, binding, transporter activity, metabolism, biological regulation, and localization. Four GO terms were enriched in the upregulated genes and no terms were enriched in the downregulated genes (FDR < 0.05). Eight statistically significant correlations (P < 0.05) were identified between the morphological measurements and DEG. CONCLUSION: Morphological measures between high and low PE verified comparisons were of similarly sized pigs grown on different sized placentas, and indicated that any negative effects of a reduced placental size on fetal growth were not evident by day 95. The identification of DEG in the placenta, but absence of DEG in the endometrium confirmed that the placenta responds to the fetus. The GO analyses provided evidence that extremes of PE are differentially regulated, affecting components of placental transport capacity like nutrient transport and blood flow. However, alternative GO terms were identified, indicating the complexity of the relationship between placental and fetal weights. These findings support the use of PE as a marker of placental function and provide novel insight into the genetic control of PE, but further research is required to make PE production applicable.


Assuntos
Regulação da Expressão Gênica , Placenta/metabolismo , Animais , Endométrio/metabolismo , Feminino , Peso Fetal , Ontologia Genética , Idade Gestacional , Tamanho da Ninhada de Vivíparos , Placenta/fisiologia , Gravidez , Suínos
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