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1.
Trends Endocrinol Metab ; 32(3): 170-189, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33478870

RESUMO

Following embryo implantation, extravillous trophoblasts (EVTs) invade the maternal decidua to a certain extent during early pregnancy, which is critical for normal placentation and successful pregnancy in humans. Although sharing a similar protein structure, the transforming growth factor-ß (TGF-ß) superfamily members exert divergent functions in regulating EVT invasion, which contributes to a relative balance of TGF-ß superfamily proteins in precisely modulating this process at the maternal-fetal interface during the first trimester of pregnancy. This review details recent advances in our understanding of the functions of TGF-ß superfamily members and their corresponding receptors, signaling pathways, and downstream molecular targets in regulating human EVT invasion from studies using various in vitro or ex vivo experimental models. Also, the relevance of these discoveries about TGF-ß superfamily members to adverse pregnancy outcomes is summarized. The application of 3D culture trophoblast organoids, single-cell sequencing, and microfluidic assays in EVT invasion studies will help better reveal the molecular mechanisms through which TGF-ß superfamily members regulate human EVT invasion, shedding light on the development of innovative strategies for predicting, diagnosing, treating, and preventing adverse human pregnancy outcomes related to EVT invasion dysfunction.

2.
J Gynecol Obstet Hum Reprod ; 50(5): 102043, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33310135

RESUMO

AIM: Endometriosis is associated with infertility. The aim of this study was to examine the overall proteomic changes of eutopic endometrium in infertile women with endometriosis. METHODS: Tandem mass tags combined with multidimensional liquid chromatography and mass spectrometry analyses were used to screen the proteomic profiles of eutopic endometrium from infertile patients with endometriosis (N = 4), compared with that from patients without endometriosis (N = 4). Quantitative proteomic analysis, functional categories and significant pathway analysis were investigated subsequently. RESULTS: In total, 6.698 proteins were identified, among which 5,812 proteins were quantified. Compared with controls, proteomic analysis showed some differentially expressed proteins: 16 up-regulated proteins and 23 down-regulated proteins. Bioinformatics analysis indicated that differentially expressed proteins were involved in humoral immune response pathways, antimicrobial humoral response and regulation of nitric oxide biosynthetic process. Besides, our results showed that alpha-1-acid glycoprotein 2, complement factor B and zinc transporter Zip14 were important resources for investigating potential mechanism of infertility in infertile women with endometriosis. CONCLUSIONS: This study provided a reference proteome map of eutopic endometrium from infertile women with endometriosis. The long-term benefits of using those markers to stratify clinical treatment warrant further investigation.

3.
Prenat Diagn ; 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009680

RESUMO

OBJECTIVE: The objective of the study is to assess the clinical application of noninvasive prenatal testing (NIPT) for VTS pregnancies after the treatment of assisted reproductive technology (ART). METHOD: This was a retrospective study on VTS pregnancies through ART treatment. Participants underwent NIPT at 11 to 13 weeks gestation by sequencing. Resampling was recommended for both positive and testing failure cases. For NIPT positive results, participants were advised to have invasive testing. Clinical outcomes were obtained by telephone interview. RESULTS: In total of 579 cases, testing failure rates after first sampling and resampling were 7.6% and 1.4%, respectively. Twelve positive results were reported by NIPT. But only one true positive was confirmed, giving a PPV of 8%. A total of 576 cases completed the follow-up (including 533 NIPT negative, 12 positive, and 31 testing failure) and three cases lost follow-up. Among the 536 cases with NIPT negative results, 504 (94.0%) resulted in live-birth and 29 (5.4%) resulted in miscarriage or stillbirths. No false-negative result was reported. CONCLUSION: NIPT has the potential to be used in prenatal screening for VTS pregnancies. For the pregnant women who obtained positive and testing failure results, resampling after 15 weeks of gestation is recommended.

4.
J Assist Reprod Genet ; 37(10): 2535-2544, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32772270

RESUMO

PURPOSE: To evaluate whether miR-148a-3p overexpression is associated with disrupted decidualization of recurrent implantation failure (RIF). METHODS: Endometrial miRNA and mRNA expression profiles during the implantation window derived from women with and without RIF were identified using microarray and RT-qPCR. Immortalized human endometrial stromal cells (HESCs) were cultured for proliferation and in vitro decidualization assays after enhancing miR-148a-3p expression or inhibiting putative target gene homeobox C8 (HOXC8) expression. RT-qPCR, western blot, and luciferase reporter assays were used to confirm the relationship between miR-148a-3p and HOXC8 gene. RESULTS: MiR-148a-3p was significantly upregulated in RIF endometrial tissues. Forced expression of miR-148a-3p notably attenuated HESC in vitro decidualization. Mechanistic studies revealed that miR-148a-3p directly bounds to the HOXC8 3' untranslated region (3'UTR) and suppressed HOXC8 expressions in both mRNA and protein levels. Further investigations demonstrated that inhibition of HOXC8 in HESCs induced similar effects on decidual process as those induced by miR-148a-3p overexpression. CONCLUSION: Taken together, our findings suggested that elevated miR-148a-3p might account for flawed decidualization in RIF by negatively regulating HOXC8, raising the possibility that miR-148a-3p might be a novel therapeutic target in RIF.

5.
Trials ; 21(1): 719, 2020 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-32807234

RESUMO

BACKGROUND: Recurrent implantation failure (RIF) brings great challenges to clinicians and causes deep frustration to patients. Previous data has suggested that prednisone may play a promising role in the establishment of pregnancy and help improve the pregnancy outcome in women with RIF. But there is insufficient evidence from randomized clinical trials that had adequate power to determine if prednisone can enhance live births as the primary outcome. METHODS/DESIGN: This trial is a prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial (1:1 ratio of prednisone versus placebo). Infertile patients with RIF who intend to undergo frozen-thawed embryo transfer (FET) after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) or pre-implantation genetic testing for aneuploidy (PGT-A) will be enrolled and randomly assigned to two parallel groups. Participants will be given the treatment of prednisone or placebo from the start of endometrial preparation till the end of the first trimester of pregnancy if pregnant. The primary outcome is live birth rate. DISCUSSION: The results of this study will provide evidence for the effect of prednisone on pregnancy outcomes in patients with RIF. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800018783 . Registered on 9 October 2018.

6.
Reprod Biol Endocrinol ; 18(1): 79, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32758287

RESUMO

BACKGROUND: Chromosomal inversion was considered to have adverse effects on pregnancy outcomes through abnormal gametogenesis. The purpose of this retrospective study was to investigate whether preimplantation genetic testing (PGT) improves pregnancy outcomes for couples with chromosomal inversion. METHODS: A total of 188 cycles from 165 couples with one chromosomal inversion carrier were divided into two groups: PGT (136 cycles, 125 couples) and non-PGT (52 cycles, 50 couples). Biochemical pregnancy, clinical pregnancy, ongoing pregnancy, miscarriage and live birth rates of their first transfer cycles, as well as cumulative live birth rates of each cycle and euploidy rates, were analyzed. RESULTS: There were no statistically significant differences in the pregnancy outcomes between the two groups. The euploidy rate of pericentric inversion carriers was not higher than that of paracentric inversion carriers in PGT group (60.71% vs 50.54%, P = 0.073). Similarly, the euploid rate of male carriers was not higher than that of female carriers (61.2% vs 56.1%, P = 0.256). CONCLUSIONS: Due to limitation of retrospective study and small sample size, our current data showed that PGT cannot provide prominent benefits for inversion carriers in the Chinese Han population. Further prospective randomized controlled trials are needed to evaluate the effects of PGT.

7.
J Clin Endocrinol Metab ; 105(12)2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32506120

RESUMO

CONTEXT: Dysregulated immune hemostasis occurs in unexplained recurrent spontaneous abortion (URSA). Synthesized by cystathionine ß-synthase (CBS) and cystathionine γ-lyase (CSE), hydrogen sulfide (H2S) promotes regulatory T-cell differentiation and regulates immune hemostasis; yet, its role in URSA is elusive. OBJECTIVE: To determine if H2S plays a role in early pregnancy and if dysregulated H2S signaling results in recurrent spontaneous abortion. DESIGN: First trimester placenta villi and decidua were collected from normal and URSA pregnancies. Protein expression was examined by immunohistochemistry and immunoblotting. Human trophoblast HTR8/SVneo and JEG3 cells were treated with H2S donors; HTR8/SVneo cells were transfected with CBS ribonucleic acid interference (RNAi) or complementary deoxyribonucleic acid. Cell migration and invasion were determined by transwell assays; trophoblast transcriptomes were determined by RNA sequencing (RNA-seq). Wild-type, CBS-deficient, and CBA/J × DBA/2 mice were treated with CBS and CSE inhibitors or H2S donors to determine the role of H2S in early pregnancy in vivo. RESULTS: CBS and CSE proteins showed cell-specific expressions, but only CBS decreased in the villous cytotrophoblast in URSA versus normal participants. H2S donors promoted migration and invasion and MMP-2 and VEGF expression in human placenta trophoblast cells that contain SV40 viral deoxyribonucleic acid sequences (HTR8/SVneo) and human placenta trophoblast cells (JEG3 cells), similar to forced CBS expression in HTR8/SVneo cells. The CBS-responsive transcriptomes in HTR8/SVneo cells contained differentially regulated genes (ie, interleukin-1 receptor and prostaglandin-endoperoxide synthase 2) that are associated with nuclear factor-κB-mediated inflammatory response. In vivo, dysregulated CBS/H2S signaling significantly increased embryonic resorption and decidual T-helper 1/T-helper 2 imbalance in mice, which was partially rescued by H2S donors. CONCLUSION: CBS/H2S signaling maintains early pregnancy, possibly via regulating maternal-fetal interface immune hemostasis, offering opportunities for H2S-based immunotherapies for URSA.

8.
J Assist Reprod Genet ; 37(8): 2025-2031, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32500460

RESUMO

PURPOSE: To perform complex preimplantation genetic tests (PGT) for aneuploidy screening, Robertsonian translocation, HLA-matching, and X-linked hyper IgM syndrome (XHIGM) caused by a novel mutation c.156 G>T of CD40LG gene. METHODS: Reverse transcription PCR (RT-PCR) and Sanger sequencing were carried out to confirm the causative variant of CD40LG gene in the proband and parents. Day 5 and D6 blastocysts, obtained by in vitro fertilization (IVF) with intracytoplasmic sperm injection, underwent trophectoderm (TE) biopsy and whole genomic amplification (WGA) and next generation sequencing (NGS)-based PGT to detect the presence of a maternal CD40LG mutation, aneuploidy, Robertsonian translocation carrier, and human leukocyte antigen (HLA) haplotype. RESULTS: Sanger sequencing data of the genomic DNA showed that the proband has a hemizygous variant of c. 156 G>T in the CD40LG gene, while his mother has a heterozygous variant at the same position. Complementary DNA (cDNA) of CD40LG amplification and sequencing displayed that no cDNA of CD40LG was found in proband, while only wild-type cDNA of CD40LG was amplified in the mother. PGT results showed that only one of the six tested embryos is free of the variant c.156 G>T and aneuploidy and having the consistent HLA type as the proband. Meanwhile, the embryo is a Robertsonian translocation carrier. The embryo was transplanted into the mother's uterus. Amniotic fluid testing results are consistent with that of PGT. A healthy baby girl was delivered, and the peripheral blood testing data was also consistent with the testing results of transplanted embryo. CONCLUSIONS: The novel mutation of c. 156 G>T in CD40LG gene probably leads to XHIGM by nonsense-meditated mRNA decay (NMD), and complex PGT of preimplantation genetic testing for monogenic disease (PGT-M), aneuploidy (PGT-A), structural rearrangement (PGT-SR), and HLA-matching (PGT-HLA) can be performed in pedigree with both X-linked hyper IgM syndrome and Robertsonian translocation.

9.
J Reprod Immunol ; 140: 103133, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32353660

RESUMO

Recurrent spontaneous abortion (RSA) can be attributed to multiple factors, and abnormal invasion and apoptosis of trophoblast cells have attracted extensive attention. Our study aimed to investigate the expression of PTEN and miRNAs with potential regulatory relationships in the placental villi of RSA patients. Nineteen RSA patients and sixteen healthy women at reproductive age undergoing induced abortion (IA) were enrolled in the present study. The expression of PTEN and miRNAs were investigated using real-time polymerase chain reaction (PCR) and Western blotting, further verification between PTEN and potential miRNAs used cell culture and transfection, and luciferase activity assays were used to determine whether PTEN is directly regulated by potential miRNA. The results indicated that both PTEN mRNA and protein expression levels were upregulated in RSA patients, but a significant difference was only observed in protein expression level (p < 0.001). Through real-time PCR pre-scanning, the results of nine potential miRNAs revealed three significantly upregulated miRNAs (miR-494, miR-146a, and miR-21) and one significantly downregulated miRNA (miR-19b). The results of further verification regarding miR-19b and miR-494 suggested that upregulated miR-19b, cooperating with downregulated miRNA-494, could inhibit PTEN expression. In conclusion, the findings suggest that the overexpression of PTEN plays an important role in the pathogenesis of RSA, with miR-19b directly regulating PTEN and working with miR-494, all of which participating in abnormal effects of villous' trophoblastic cell may be a critical event.

10.
J Assist Reprod Genet ; 37(3): 579-588, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32103397

RESUMO

PURPOSE: To investigate the associations of previous pregnancy failures, including implantation failures (IFs), biochemical pregnancy losses (BPLs), and early (EMs) and late miscarriages (LMs), with blastocyst aneuploidy and pregnancy outcomes after PGT-A. METHODS: This study included 792 couples who underwent PGT-A after multiple pregnancy failures. Subgroup analyses were used to compare the blastocyst aneuploidy rate (BAR), implantation rate (IR), early miscarriage rate (EMR), and live birth rate (LBR). Multiple linear and logistic regression models were used to evaluate the associations. The control group comprised couples with ≤ 2 IFs, ≤ 1 BPL, ≤ 1 EM, and no LM. RESULTS: Notably, a history of ≥ 4 IFs was significantly associated with an increase in aneuploid blastocysts (42.86% vs. 33.05%, P = 0.044, B = 10.23 for 4 IFs; 48.80% vs. 33.05%, P = 0.002, B = 14.43 for ≥ 5 IFs). Women with ≥ 4 prior EMs also harbored more aneuploid blastocysts (41.00% vs. 33.05%, P = 0.048; B = 9.23). Compared with the control group, women with ≥ 4 prior EMs had a significantly higher EMR (6.58% vs. 31.11%, P < 0.001, OR = 6.49) and a lower LBR (53.49% vs. 34.18%, P = 0.007, OR = 0.56) after euploid transfer. Moreover, a history of LM(s) was associated with adverse pregnancy outcomes after PGT-A (OR for EM = 3.16; OR for live birth = 0.48). However, previous BPLs and 2 EMs were not associated significantly with blastocyst aneuploidy and pregnancy outcomes after PGT-A. CONCLUSION: A history of high-order IFs or EMs and existence of LM(s) were significantly associated with blastocyst aneuploidy and adverse pregnancy outcomes after PGT-A, whereas no such associations were observed with BPLs or 2 EMs.

11.
Acta Neurochir Suppl ; 127: 59-64, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31407064

RESUMO

BACKGROUND: It is reported that the expression of aquaporin4 (AQP4) in the brain is increased and leads to the brain edema after subarachnoid hemorrhage (SAH). In this study, by using AQP4 knockout rat model, the opposite role of AQP4 in early brain injury following SAH through modulation of interstitial fluid (ISF) transportation in the brain glymphatic system had been explored. METHODS: The SAH model was established using endovascular perforation method, the AQP4 knockout rat model was generated using TALENs (transcription activator-like (TAL) effector nucleases) technique. The animals were randomly divided into four groups: sham (n = 16), AQP4-/-sham (n = 16), SAH (n = 24), and AQP4-/-SAH groups (n = 27). The roles of AQP4 in the brain water content and neurological function were detected. In addition, immunohistochemistry and Nissl staining were applied to observe the effects of AQP4 on the blood-brain barrier (BBB) integrity and the loss of neurons in the hippocampus. To explore the potential mechanism of these effects, the distribution of Gd-DTPA (interstitial fluid indicator) injected from cisterna magna was evaluated with MRI. RESULTS: Following SAH, AQP4 knockout could significantly increase the water content in the whole brain and aggravate the neurological deficits. Furthermore, the loss of neuron and BBB disruption in hippocampus were also exacerbated. The MRI results indicated that the ISF transportation in the glymphatic system of AQP4 deficit rat was significantly injured. CONCLUSION: AQP4 facilitates the ISF transportation in the brain to eliminate the toxic factors; AQP4 knockout will aggravate the early brain injury following SAH through impairment of the glymphatic system.


Assuntos
Aquaporina 4 , Edema Encefálico , Lesões Encefálicas , Hemorragia Subaracnóidea , Animais , Aquaporina 4/fisiologia , Encéfalo , Lesões Encefálicas/etiologia , Técnicas de Inativação de Genes , Sistema Glinfático , Ratos , Hemorragia Subaracnóidea/genética , Hemorragia Subaracnóidea/patologia
12.
Stem Cells Dev ; 29(4): 212-221, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31801411

RESUMO

In this study, the roles of exosomes (Exo) from bone marrow mesenchymal stem cells (BMSCs) in attenuating early brain injury (EBI) in rat brain after subarachnoid hemorrhage (SAH) had been investigated. The male Sprague-Dawley rats (300-350 g) were used to establish the SAH model using endovascular perforation method. The animals were randomly divided into three groups: sham (n = 25), SAH+PBS (n = 42), and SAH+Exo groups (n = 33). At 1 h after SAH, Exo or phosphate-buffered saline (PBS) was administered by femoral vein injection. The effects of Exo on the mortality, neurological function, brain water content, and blood-brain barrier (BBB) were explored. Furthermore, the expressions of miRNA129-5p and high-mobility group box 1 protein (HMGB1) after Exo treatment were also detected. In addition, immunohistochemistry and western blot were applied to investigate the mechanism of Exo's effects. The results indicated that Exo could improve the neurological functions, reduce brain water content and maintain BBB integrity after SAH. After Exo treatment, the expression of miRNA129-5p was significantly increased, whereas the RNA level of HMGB1 was decreased. The protein levels of proinflammatory and proapoptosis factors, such as HMGB1, Toll-like receptor-4 (TLR4), tumor necrosis factor-α, and p53, were increased after SAH, which were significantly declined after Exo application. The results indicated that Exo from BMSCs could alleviate EBI after SAH through miRNA129-5p's anti-inflammation and antiapoptosis effects through quenching the activity of HMGB1-TLR4 pathway.

13.
Am J Hum Genet ; 105(6): 1102-1111, 2019 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-31679651

RESUMO

Recurrent miscarriage (RM) affects millions of couples globally, and half of them have no demonstrated etiology. Genome sequencing (GS) is an enhanced and novel cytogenetic tool to define the contribution of chromosomal abnormalities in human diseases. In this study we evaluated its utility in RM-affected couples. We performed low-pass GS retrospectively for 1,090 RM-affected couples, all of whom had routine chromosome analysis. A customized sequencing and interpretation pipeline was developed to identify chromosomal rearrangements and deletions/duplications with confirmation by fluorescence in situ hybridization, chromosomal microarray analysis, and PCR studies. Low-pass GS yielded results in 1,077 of 1,090 couples (98.8%) and detected 127 chromosomal abnormalities in 11.7% (126/1,077) of couples; both members of one couple were identified with inversions. Of the 126 couples, 39.7% (50/126) had received former diagnostic results by karyotyping characteristic of normal human male or female karyotypes. Low-pass GS revealed additional chromosomal abnormalities in 50 (4.0%) couples, including eight with balanced translocations and 42 inversions. Follow-up studies of these couples showed a higher miscarriage/fetal-anomaly rate of 5/10 (50%) compared to 21/93 (22.6%) in couples with normal GS, resulting in a relative risk of 2.2 (95% confidence interval, 1.1 to 4.6). In these couples, this protocol significantly increased the diagnostic yield of chromosomal abnormalities per couple (11.7%) in comparison to chromosome analysis (8.0%, chi-square test p = 0.000751). In summary, low-pass GS identified underlying chromosomal aberrations in 1 in 9 RM-affected couples, enabling identification of a subgroup of couples with increased risk of subsequent miscarriage who would benefit from a personalized intervention.


Assuntos
Aborto Habitual/diagnóstico , Aborto Habitual/genética , Aberrações Cromossômicas , Sequenciamento Completo do Genoma/métodos , Adulto , Feminino , Seguimentos , Humanos , Cariotipagem , Masculino , Gravidez , Prognóstico , Estudos Retrospectivos
14.
J Assist Reprod Genet ; 36(11): 2325-2331, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31522368

RESUMO

PURPOSE: To report the normal live birth and birth defect rates pre- and post- preimplantation genetic testing for chromosomal structural rearrangements (PGT-SR) in reciprocal translocation carriers who have experienced two or more unfavorable pregnancy histories. METHODS: We conducted a retrospective cohort study of 194 couples who underwent 265 PGT-SR cycles between January 2013 and August 2016. The rates of miscarriage, normal live birth, and birth defect pre- and post- PGT-SR treatment were recorded. The types of birth defect were also categorized. RESULTS: Before PGT-SR treatment, the 194 couples with reciprocal translocation had a previous reproductive history consisting of 592 pregnancies in total: 496 (83.8%) were miscarriages; 29 (4.9%) ended by induced abortion due to unintended pregnancy; 36 (6.1%) had birth defects; and 17 (2.9%) were normal live births. After PGT-SR treatment, there were 118 clinical pregnancies. Of these pregnancies, 13 (11.0%) were miscarriages, 101 (85.6%) were normal live births, and 4 (3.4%) had birth defects. In total, 14 different disorders were noted in the prenatal and postnatal examinations. Before the PGT-SR treatment, multiple birth defects, central nervous system abnormalities, and congenital heart defects were the three most common congenital malformations. Excluding for methylmalonic acidemia, there were only single and mild birth defects after the PGT-SR treatment. CONCLUSIONS: After the PGT-SR treatment, the reciprocal translocation carriers who had previously experienced two or more unfavorable pregnancy outcomes had a low risk of miscarriages and birth defects. The rate of normal live births per pregnancy was higher after PGT-SR treatment.


Assuntos
Aborto Espontâneo/genética , Nascimento Vivo/genética , Resultado da Gravidez/genética , Translocação Genética/genética , Adulto , Coeficiente de Natalidade , Aberrações Cromossômicas , Transferência Embrionária/métodos , Feminino , Fertilização In Vitro , Testes Genéticos/métodos , Heterozigoto , Humanos , Masculino , Gravidez , Taxa de Gravidez , Diagnóstico Pré-Implantação/métodos , História Reprodutiva , Estudos Retrospectivos , Adulto Jovem
15.
J Assist Reprod Genet ; 36(9): 1963-1969, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31392661

RESUMO

PURPOSE: To investigate the effects of a carrier's sex and age on the segregation patterns of the trivalent of Robertsonian translocations. METHODS: This retrospective study was designed to analyze the segregation patterns of the trivalent and euploidy rates of blastocysts. Data were collected from 154 couples with Robertsonian translocation (77 with a female carrier and 77 with a male carrier). Embryos were diagnosed via array comparative genomic hybridization between January 2013 and July 2017. The segregation patterns of the trivalent of 604 blastocysts were analyzed according to the carrier's sex and age. RESULTS: The proportion of alternate segregation was significantly higher (82.9% vs. 55.2%) in the male carriers than in the female carriers of Robertsonian translocation, and the proportion of adjacent segregation was significantly lower (16.8% vs. 42.6%), with no difference in 3:0 segregation. The segregation patterns were similar in same-sex carriers when analyzed according to the type of translocation. The carrier's age had no influence on the segregation patterns of the trivalent. CONCLUSIONS: The proportions of the trivalent's meiotic segregation pattern differ significantly according to the carrier's sex in Robertsonian translocations and are independent of the carrier's age. A significantly higher proportion of alternate segregation for normal or balanced chromosome contents was observed in the blastocysts of the male carriers than in those of the female carriers.


Assuntos
Blastocisto/fisiologia , Segregação de Cromossomos , Heterozigoto , Translocação Genética , Adulto , Aberrações Cromossômicas , Hibridização Genômica Comparativa , Feminino , Humanos , Masculino , Indução da Ovulação , Ploidias , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Translocação Genética/genética
16.
Biochem Biophys Res Commun ; 515(3): 429-435, 2019 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-31155295

RESUMO

Accelerating the clearance of toxin in the brain extracellular space (ECS) has grown a promising strategy for treating some central nervous system diseases. As oldest sensory system, we know little about the influence of olfaction on the brain, but preclinical studies such as treatment of neurological diseases through it are in the ascendant. This makes it important to clarify the effects of olfaction on brain ECS and interstitial fluid (ISF) drainage. In this study, the effect of olfactory stimulation (eugenol, EUG) on ISF flow in hippocampus and its association with aquaporin 4 (Aqp4) had been investigated. The results show that eugenol can significantly increase the activity of hippocampal neurons, but reduce the clearance and diffusion rates of Gd-DTPA and A-594 in hippocampus. Similarly, eugenol inhalation slows down the rate of Gd-DTPA in CSF entering the hippocampus and its clearance. And knockout of Aqp4 gene aggravated these processes. In vitro results showed that after Aqp4 gene silencing, astrocytes grew slowly, with significantly decreased cells number, less nuclei, atrophied bodies and shorter processes. These results concluded that olfactory stimulation can change the ECS structure of the hippocampus, slow down the ISF drainage, and improve the function of neurons, while Aqp4 plays important roles.


Assuntos
Espaço Extracelular/metabolismo , Hipocampo/fisiologia , Olfato/fisiologia , Animais , Aquaporina 4/metabolismo , Astrócitos/metabolismo , Sequência de Bases , Eugenol/farmacologia , Gadolínio DTPA/metabolismo , Técnicas de Inativação de Genes , Masculino , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Ratos Sprague-Dawley
17.
Neurosci Lett ; 704: 189-194, 2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-30980845

RESUMO

BACKGROUND: In this study, the protective effects of 3,4-dihydroxyphenyl lactic acid (DLA) on blood-brain barrier (BBB) injury following subarachnoid hemorrhage (SAH) has been explored. METHODS: Male Sprague-Dawley rats (weight 300-350 g) were used to establish the SAH model using the endovascular perforation method. The animals were randomly divided into four groups: sham (n = 40), SAH (n = 46), SAH + vehicle (n = 44), and SAH + DLA (n = 40) treatment groups. At 1 h after SAH, either DLA (10 mg/kg) or normal saline (vehicle) was administered by femoral vein injection. The effects of DLA on mortality, neurological function, brain water content, and BBB were observed. Additionally, immunohistochemistry and western blot techniques were applied to investigate the mechanism of action of DLA. RESULTS: We found that the administration of DLA (10 mg/kg) following SAH could improve neurological functions, reduce brain water content, and maintain BBB integrity. The expression of pro-inflammatory and pro-apoptotic factors such as toll-like receptor 4 (TLR4), NF-κB (p-p65), tumor necrosis factor-α, p-p38 MAPK, p-p53, and caspase-3 were significantly increased after SAH. These same factors were markedly attenuated following treatment with DLA. CONCLUSIONS: These findings showed that DLA can alleviate BBB injury following SAH through its anti-inflammatory and anti-apoptotic effects via suppression of TLR4 and its downstream NF-κB and p38 MAPK pathways.


Assuntos
Anti-Inflamatórios/uso terapêutico , Barreira Hematoencefálica/efeitos dos fármacos , Lactatos/uso terapêutico , Hemorragia Subaracnóidea/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/patologia , Edema Encefálico/tratamento farmacológico , Edema Encefálico/metabolismo , Edema Encefálico/patologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Masculino , Permeabilidade , Ratos Sprague-Dawley , Hemorragia Subaracnóidea/patologia , Hemorragia Subaracnóidea/fisiopatologia
18.
Reprod Sci ; 26(12): 1582-1589, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30782086

RESUMO

The typical hallmark of placenta accreta spectrum (PAS) disorders is increased implantation site intermediate trophoblast (ISIT) cell numbers. However, the extent of trophoblast proliferation and apoptosis have not been found to differ from those of normal placentation. MicroRNA-125a (miR-125a) induces apoptosis in colon cancer cell by targeting myeloid cell leukemia-1 gene (MCL1). We aimed to investigate the influence of miR-125a on ISIT cells in PAS disorders in 15 patients (self-paired trials) with placenta previa and PAS disorders. Expression of miR-125a and MCL1 were measured in villous trophoblasts and basal plate myometrial fibers from creta site and adjacent noncreta tissues by real-time quantitative polymerase chain reaction, and expression of the MCL1 protein was assayed by Western blotting. Flow-cytometry was used to examine the effect of miR-125a overexpression on apoptosis in vitro in HTR-8/SVneo cells, and luciferase activity assays was used to confirm miR-125a targeting of MCL1. In vivo, the expression levels of miR-125a was significantly lower in creta versus noncreta tissues, and the expression of MCL1 was upregulated; moreover, immunohistochemistry showed that the increased ISIT cells in the creta were positive for MCL1 protein. MCL1 was downregulated in the miR-125a-overexpressing HTR-8/SVneo cells in vitro, and overexpression of miR-125a-induced apoptosis in the HTR-8/SVneo trophoblast line. Finally, luciferase activity assays confirmed that miR-125a directly target the 3' untranslated region of MCL1 in the 293T cell line. In conclusion, downregulation of MCL1-targeting miR-125a exerts an antiapoptotic effect on ISIT cells in PAS disorders.


Assuntos
Apoptose/genética , MicroRNAs/metabolismo , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Placenta Acreta/metabolismo , Trofoblastos/metabolismo , Regiões 3' não Traduzidas , Adulto , Linhagem Celular , Proliferação de Células/fisiologia , Regulação para Baixo , Células Epiteliais/metabolismo , Feminino , Humanos , MicroRNAs/genética , Proteína de Sequência 1 de Leucemia de Células Mieloides/genética , Miométrio/metabolismo , Placenta Acreta/genética , Gravidez
19.
J Cell Biochem ; 120(1): 213-223, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30206981

RESUMO

Liver cancer is still one of the leading causes of cancer-related death worldwide. This study is dedicated to developing a multi-long noncoding RNA (lncRNA) model for risk stratification and prognosis prediction on patients with hepatocellular carcinoma (HCC). We first downloaded lncRNA expression profiles and corresponding clinical information of patients with liver cancer from The Cancer Genome Atlas database. Differentially expressed (DE) lncRNAs between HCC samples and normal samples were identified. In total, 308 patients with HCC were randomly divided into a training group (n = 154) and a testing group (n = 154). Univariate Cox regression and least absolute shrinkage and selection operator Cox regression analyses were performed to select the best survival-related candidates from these DE lncRNAs in the training set. Seven lncRNAs (AC009005.2, RP11-363N22.3, RP11-932O9.10, RP11-572O6.1, RP11-190C22.8, RP11-388C12.8, and ZFPM2-AS1) were finally identified and used to construct a seven-lncRNA signature. The signature could classify patients into high-risk and low-risk groups with significantly different overall survival. The area under the curve of receiver operating characteristic curve for the signature to predict 5-year survival reached more than 0.75. Besides, the prognostic value of the seven-lncRNA signature was independent of conventional clinical factors. The predictive performance of the signature was further validated in the testing set and the whole set. Functional enrichment analysis indicated that the seven prognostic lncRNAs may be involved in several essential biological processes and pathways. The current study demonstrated the potential clinical implications of the seven-lncRNA signature for survival prediction of patients with HCC.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , RNA Longo não Codificante/genética , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/mortalidade , Bases de Dados Genéticas , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Taxa de Sobrevida , Transcriptoma
20.
Brain Inj ; 33(6): 712-716, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30335519

RESUMO

Aim: In this work, we systematically explored the physiological functions of astrocytes and their roles following ischemic stroke, additionally, the potential therapy strategy targeting the astrocytes was also discussed. Methods: This work searched the PubMed database (including MEDLINE) until 14 Feb 2018, and furthermore, the studies were identified through cross-referencing and by consulting the experts in this field. Results: This study indicated that the astrocytes can not only play harmful roles following ischemic stroke through release of inflammatory factors and formation of glial scar but also have protective effects through quenching glutamate excitotoxicity and maintaining the clearance function of glymphatic system in brain. Conclusion: Owing to their important roles in physiological functions of brain and in the pathological conditions following ischemic stroke, the astrocytes might be a potential but promising therapeutic target for treating the ischemic stroke in the future.


Assuntos
Astrócitos/patologia , Isquemia Encefálica/patologia , Isquemia Encefálica/terapia , Acidente Vascular Cerebral/patologia , Humanos , Neuroproteção , Acidente Vascular Cerebral/terapia
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