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1.
Genesis ; 62(1): e23585, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38124435

RESUMO

The placenta plays a pivotal role in the maintenance of normal pregnancy, but how it forms, matures, and performs its function remains poorly understood. Here, we describe a novel mouse line (Prl3d1-iCre) that expresses iCre recombinase under the control of the endogenous prl3d1 promoter. Prl3d1 has been proposed as a marker for distinguishing trophoblast giant cells (TGCs) from other trophoblast cells in the placenta. The in vivo efficiency and specificity of the Cre line were analyzed by interbreeding Prl3d1-iCre mice with B6-G/R reporter mice. Through anatomical studies of the placenta and other tissues of Prl3d1-iCre/+; B6-G/R mouse mice, we found that the tdTomato signal was expressed in parietal trophoblast giant cells (P-TGCs). Thus, we report a mouse line with ectopic Cre expression in P-TGCs, which provides a valuable tool for studying human pathological pregnancies caused by implantation failure or abnormal trophoblast secretion due to aberrant gene regulation.


Assuntos
Placenta , Proteína Vermelha Fluorescente , Trofoblastos , Animais , Feminino , Camundongos , Gravidez , Células Gigantes/metabolismo , Integrases/genética , Integrases/metabolismo , Camundongos Transgênicos , Placenta/metabolismo
2.
Environ Res ; 258: 119426, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38879106

RESUMO

BACKGROUND: Epidemiological evidence emphasizes air pollutants' role in chronic kidney disease (CKD). Volatile organic compounds (VOCs) contribute to air pollution, yet research on VOCs and kidney damage, especially gender disparities, is limited. METHODS: This study analyzed NHANES data to explore associations between urinary VOC metabolite mixtures (VOCMs) and key kidney-related parameters: estimated glomerular filtration rate (eGFR), albumin-to-creatinine ratio (ACR), chronic kidney disease (CKD), and albuminuria. Mediation analyses assessed the potential mediating roles of biological aging (BA) and serum albumin in VOCM mixtures' effects on kidney damage. Sensitivity analyses were also conducted. RESULTS: The mixture analysis unveiled a noteworthy positive association between VOCM mixtures and the risk of developing CKD, coupled with a significant negative correlation with eGFR within the overall participant cohort. These findings remained consistent when examining the female subgroup. However, among male participants, no significant link emerged between VOCM mixtures and CKD or eGFR. Furthermore, in both the overall and female participant groups, there was an absence of a significant correlation between VOCM mixtures and either ACR or albuminuria. On the other hand, in male participants, while no significant correlation was detected with albuminuria, a significant positive correlation was observed with ACR. Pollutant analysis identified potential links between kidney damage and 1,3-butadiene, toluene, ethylbenzene, styrene, xylene, acrolein, crotonaldehyde and propylene oxide. Mediation analyses suggested that BA might partially mediate the relationship between VOCM mixtures and kidney damage. CONCLUSION: The current findings highlight the widespread exposure to VOCs among the general U.S. adult population and indicate a potential correlation between exposure to VOC mixtures and compromised renal function parameters, with notable gender disparities. Females appear to exhibit greater sensitivity to impaired renal function resulting from VOCs exposure. Anti-aging treatments may offer some mitigation against kidney damage due to VOCs exposure.


Assuntos
Poluentes Atmosféricos , Compostos Orgânicos Voláteis , Humanos , Compostos Orgânicos Voláteis/urina , Compostos Orgânicos Voláteis/toxicidade , Feminino , Masculino , Pessoa de Meia-Idade , Poluentes Atmosféricos/toxicidade , Adulto , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/urina , Taxa de Filtração Glomerular/efeitos dos fármacos , Idoso , Inquéritos Nutricionais , Caracteres Sexuais , Albuminúria/induzido quimicamente , Albuminúria/urina , Exposição Ambiental/efeitos adversos
3.
Reprod Biol Endocrinol ; 19(1): 21, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33579314

RESUMO

BACKGROUND: The pathophysiological mechanism of recurrent miscarriage (RM) is unclear. The goals of this study were to determine the role of microRNA-4497 overexpression in placental villus tissues in early RM; To identify the potential target mRNAs of miRNA-4497; And to investigate the microRNA-4497-mediated regulatory mechanisms in placental trophoblasts. METHODS: Bioinformatics analysis was performed to identify the candidate target genes of miRNA-4497. The protein expression of Sp1 transcription factor (SP1), chemokine (C-X-C motif) receptor 5 (CXCR5) and bone morphogenetic protein 8a (BMP8A) were determined in the villus tissues of the RM and normal groups by Western blotting and immunohistochemistry. Cultured 293T cells were co-transfected with the miRNA-4497 agomir or luciferase reporter vectors containing the wild-type or mutant 3'-UTRs of the target mRNAs to verify the regulatory role of miRNA-4497. RESULTS: Bioinformatics analysis suggested that SP1, CXCR5 and BMP8A mRNAs are potential targets of miRNA-4497. The expression of SP1, CXCR5 and BMP8A proteins in the chorionic villus tissues of RM placentas were significantly decreased compared to those in the normal controls. Moreover, SP1 protein levels were inversely correlated with the levels of miRNA-4497 in the placentas of RM patients and normal controls. The expression of SP1 mRNA and protein were down-regulated in HTR-8/SVneo cells after forced overexpression of the miRNA-4497 agomir. The results of the co-transfection assay showed that mutation of the miRNA-4497-binding sites in the 3'-untranslated region (3'-UTR) of SP1 led to a recovery of luciferase activity upon overexpression of miRNA-4497, suggesting that SP1 could be a direct target of miRNA-4497. CONCLUSIONS: An increased miRNA-4497 level in the placental villus tissues associated with recurrent miscarriage may down-regulate SP1 expression. The negative regulation of SP1 by miRNA-4497 may potentially contribute to the pathogenesis of recurrent miscarriage through promotion of trophoblast apoptosis. These findings provide novel information on the regulation of placental trophoblast apoptosis, and could be useful for the development of new therapeutic strategies for better management of recurrent miscarriage.


Assuntos
Aborto Habitual/genética , MicroRNAs/genética , Placenta/metabolismo , Fator de Transcrição Sp1/genética , Aborto Habitual/metabolismo , Aborto Habitual/patologia , Adulto , Estudos de Casos e Controles , Células Cultivadas , Vilosidades Coriônicas/metabolismo , Vilosidades Coriônicas/patologia , Regulação para Baixo/genética , Feminino , Idade Gestacional , Células HEK293 , Humanos , MicroRNAs/metabolismo , Placenta/patologia , Gravidez , Fator de Transcrição Sp1/metabolismo , Trofoblastos/metabolismo , Trofoblastos/patologia
4.
Proc Natl Acad Sci U S A ; 114(12): E2365-E2374, 2017 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-28265104

RESUMO

The Hippo signaling pathway is highly conserved from Drosophila to mammals and plays a central role in maintaining organ size and tissue homeostasis. The blood-brain barrier (BBB) physiologically isolates the brain from circulating blood or the hemolymph system, and its integrity is strictly maintained to perform sophisticated neuronal functions. Until now, the underlying mechanisms of subperineurial glia (SPG) growth and BBB maintenance during development are not clear. Here, we report an miR-285-Yorkie (Yki)/Multiple Ankyrin repeats Single KH domain (Mask) double-negative feedback loop that regulates SPG growth and BBB integrity. Flies with a loss of miR-285 have a defective BBB with increased SPG ploidy and disruptive septate junctions. Mechanistically, miR-285 directly targets the Yki cofactor Mask to suppress Yki activity and down-regulates the expression of its downstream target cyclin E, a key regulator of cell cycle. Disturbance of cyclin E expression in SPG causes abnormal endoreplication, which leads to aberrant DNA ploidy and defective septate junctions. Moreover, the expression of miR-285 is increased by knockdown of yki or mask and is decreased with yki overexpression, thus forming a double-negative feedback loop. This regulatory loop is crucial for sustaining an appropriate Yki/Mask activity and cyclin E level to maintain SPG ploidy and BBB integrity. Perturbation of this signaling loop, either by dysregulated miR-285 expression or Yki activity, causes irregular SPG ploidy and BBB disruption. Furthermore, ectopic expression of miR-285 promotes canonical Hippo pathway-mediated apoptosis independent of the p53 or JNK pathway. Collectively, these results reveal an exquisite regulatory mechanism for BBB maintenance through an miR-285-Yki/Mask regulatory circuit.


Assuntos
Barreira Hematoencefálica/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , MicroRNAs/metabolismo , Proteínas Nucleares/metabolismo , Transativadores/metabolismo , Animais , Ciclo Celular , Proteínas de Ligação a DNA/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Drosophila melanogaster/crescimento & desenvolvimento , Feminino , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , MicroRNAs/genética , Neuroglia/metabolismo , Proteínas Nucleares/genética , Ploidias , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Transativadores/genética , Proteínas de Sinalização YAP
5.
Biochem Cell Biol ; 97(4): 415-422, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30481052

RESUMO

A previous study by our group indicted that overexpression of bromodomain PHD-finger transcription factor (BPTF) occurs in lung adenocarcinoma, and is closely associated with advanced clinical stage, higher numbers of metastatic lymph nodes, the occurrence of distant metastasis, low histological grade, and poor prognosis. Down-regulation of BPTF inhibited lung adenocarcinoma cell proliferation and promoted lung adenocarcinoma cell apoptosis. The purpose of this study is to identify valuable microRNAs (miRNAs) that target BPTF to modulate lung adenocarcinoma cell proliferation. In our results, we found that miR-3666 was notably reduced in lung adenocarcinoma tissues and cell lines. Using an miR-3666 mimic, we discovered that cell proliferation, migration, and invasiveness were suppressed by miR-3666 overexpression, but these were all enhanced when the expression of miR-3666 was reduced. Moreover, bioinformatics analysis using the TargetScan database and miRanda software suggested a putative target site in BPTF 3'-UTR. Furthermore, using a luciferase reporter assay, we verified that miR-3666 directly targets the 3'-UTR of BPTF. Using Western blot we discovered that overexpression of miR-3666 negatively regulates the protein expression of BPTF. Finally, we identified that the PI3K-AKT and epilthelial-mesenchymal transition (EMT) signaling pathways were inhibited by miR-3666 overexpression in lung cancer cells. In conclusion, our data indicate that miR-3666 could play an essential role in cell proliferation, migration, and invasiveness by targeting BPTF and partly inhibiting the PI3K-AKT and EMT signaling pathways in human lung cancers.


Assuntos
Antígenos Nucleares/genética , Movimento Celular/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , MicroRNAs/genética , Proteínas do Tecido Nervoso/deficiência , Proteínas do Tecido Nervoso/genética , Fatores de Transcrição/deficiência , Fatores de Transcrição/genética , Antígenos Nucleares/metabolismo , Proliferação de Células/genética , Biologia Computacional , Humanos , Neoplasias Pulmonares/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Fatores de Transcrição/metabolismo , Células Tumorais Cultivadas
6.
Gene ; 914: 148405, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38521110

RESUMO

The trophoblast epithelial-to-mesenchymal transition (EMT) is a procedure related to embryo implantation, spiral artery establishment and fetal-maternal communication, which is a key event for successful pregnancy. Inadequate EMT is one of the pathological mechanisms of recurrent miscarriage (RM). Whole-exome sequencing revealed that the mutation of bromodomain PHD-finger transcription factor (BPTF) was strongly associated with RM. In the present study, the effects of BPTF on EMT and the underlying mechanism were investigated. We found that the expression of BPTF in the villi of RM patients was significantly downregulated. Gene Ontology (GO) analysis revealed that BPTF participated in cell adhesion. The knockdown of BPTF prevented EMT and attenuated trophoblast invasion in vitro. BPTF activated Slug transcription by binding directly to the promoter region of the Slug gene. Interestingly, the protein levels of both Slug and BPTF were decreased in the villous cytotrophoblasts (VCTs) of RM villi. In conclusion, BPTF participates in the regulation of trophoblast EMT by activating Slug expression, suggesting that BPTF defects are an important factor in RM pathogenesis.


Assuntos
Antígenos Nucleares , Proteínas que Contêm Bromodomínio , Transição Epitelial-Mesenquimal , Proteínas do Tecido Nervoso , Fatores de Transcrição da Família Snail , Fatores de Transcrição , Trofoblastos , Trofoblastos/metabolismo , Humanos , Feminino , Fatores de Transcrição da Família Snail/metabolismo , Fatores de Transcrição da Família Snail/genética , Gravidez , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Aborto Habitual/genética , Aborto Habitual/metabolismo , Adesão Celular , Regiões Promotoras Genéticas , Adulto
7.
Mol Genet Genomic Med ; 11(9): e2220, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37288669

RESUMO

BACKGROUND: Enolase 1 (ENO1) is a metabolic enzyme which participates in pyruvate synthesis and ATP production in cells. Previously, differential expression of ENO1 was discovered in villous tissues between recurrent miscarriage and induced abortion. This study was designed to explore whether ENO1 influences the proliferation and invasion of villous trophoblasts and the related molecular mechanisms. METHODS: First, ENO1 expression in placental villus tissues collected from recurrent miscarriage (RM) patients and women for induced abortion as well as in trophoblast-derived cell lines was detected by RT-qPCR and western blotting. ENO1 localization and expression in villus tissues were further confirmed through immunohistochemistry staining. Then, the effects of ENO1 downregulation on trophoblast Bewo cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) process were evaluated by CCK-8 assay, transwell assay, and western blotting. As for the regulatory mechanism of ENO1, the expression of COX-2, c-Myc and cyclin D1 in Bewo cells after ENO1 knockdown was finally evaluated by RT-qPCR and western blotting. RESULTS: ENO1 was mainly localized in the cytoplasm, with very small amounts in the nucleus of trophoblast cells. ENO1 expression in the villi tissues of RM patients was significantly increased, when compared with the villous tissues of healthy controls. Furthermore, Bewo cells, a trophoblast cell line with relatively higher expression of ENO1, was used to downregulate the ENO1 expression by ENO1-siRNA transfection. ENO1 knockdown significantly facilitated Bewo cell growth, EMT process, migration, and invasion. ENO1 silencing markedly elevated COX-2, c-Myc, and cyclin D1 expression. CONCLUSION: ENO1 may participate in the development of RM via suppressing the growth and invasion of villous trophoblasts via reducing the expression of COX-2, c-Myc, and cyclin D1.


Assuntos
Aborto Habitual , Trofoblastos , Feminino , Humanos , Gravidez , Aborto Habitual/genética , Proliferação de Células , Ciclina D1/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Fosfopiruvato Hidratase/genética , Fosfopiruvato Hidratase/metabolismo , Placenta/metabolismo , Trofoblastos/metabolismo
8.
Theriogenology ; 211: 172-181, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37643502

RESUMO

Bromodomain PHD finger transcription factor (BPTF), a core subunit of nucleosome-remodeling factor (NURF) complex, plays an important role in chromatin remodeling. However, few information of BPTF is available in pig, especially in mammalian follicular granulosa cells (GCs). The present study firstly confirmed that BPTF in porcine was relative close to human and mouse. The expression of BPTF could be detected in ovary, testes, lung, kidney, large intestine, and small intestine. And a relative high expression of BPTF was observed in ovarian follicles and GCs. When BPTF was knocked down (BPTF-siRNA), the viability of GCs was affected. And the expression level of CDK1, cyclin B1, CDK4 and CDK2 was higher than the control, which might indicate that the cell cycle of GCs was inhibited from S to G2/M phase. Although the apoptosis level was induced in the BPTF-siRNA GCs, the reduced level of H3K4 methylation was detected with the down regulation of SMYD3, EHMT2 and DPY30. Thereby, results in the present might provide the primary knowledge of BPTF in GCs and the follicular development in pig.


Assuntos
Montagem e Desmontagem da Cromatina , Células da Granulosa , Feminino , Humanos , Suínos , Animais , Camundongos , Ciclo Celular , Divisão Celular , Apoptose , Mamíferos , Antígenos de Histocompatibilidade , Histona-Lisina N-Metiltransferase
9.
Theriogenology ; 210: 42-52, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37473595

RESUMO

One of the most typical abnormal cleavage patterns during early embryonic development is uneven division, but the first uneven division of pig zygote is common. Uneven division results in different daughter cell sizes and an uneven distribution of organelles such as lipid droplet, mitochondria, but the developmental capacity of daughter cells and proteomic changes of daughter cells are still unclear. Therefore, the developmental ability and proteomic quantification were investigated on blastomeres from even division (ED) or uneven division (UD) embryos at 2-cell stage in the present study. Firstly, the developmental ability was affected by the blastomeric size, when compared with medium blastomeres (MBs), the large blastomeres (LBs) with the higher cleavage rate but the small blastomeres (SBs) with the lower rate was observed. Subsequently, proteomic analysis was performed on blastomeres of LBs, MBs and SBs, a total of 109 DEPs were detected, which were involved in protein metabolism and processing, energy metabolism and ribosome. In particular, DEPs in LBs vs. SBs were focused on RNA binding and actin cytoskeletal tissue. Two protein-dense networks associated with RNA binding and cytoskeleton were revealed by further protein-protein interaction (PPI) analysis of DEPs in LBs vs. SBs, that DDX1 related to RNA binding and ACTB related to cytoskeleton were confirmed in UD embryos. Therefore, a briefly information of DEPs in blastomeres of 2-cell stage pig embryos was described in the present study, and it further confirmed that the formation of uneven division of the first cell cycle of pig embryos might be controlled by the cytoskeleton; the developmental capacity of daughter cells might be affected by the energy metabolism, RNA binding and ribosome, and further account for the developmental potential of the whole embryo.


Assuntos
Desenvolvimento Embrionário , Proteômica , Gravidez , Feminino , Animais , Suínos , Blastômeros/metabolismo , Embrião de Mamíferos , RNA/metabolismo
10.
J Gynecol Obstet Hum Reprod ; 50(8): 102071, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33486101

RESUMO

BACKGROUND: Intrauterine insemination (IUI) is a first-line treatment for unexplained infertility (UI). There was a compelling need for the improvement of pregnancy rate in females with UI. OBJECTIVE: To explore the pregnancy predictors in cases of UI undergoing IUI. METHOD: A total of 212 couples who underwent 446 IUI cycles were involved the study. Different factors were grouped to explore the influencing factors of IUI for UI. RESULT: Female age and somking affected pregnancy outcomes. As the number of treatment cycles increased, the pregnancy rate increased. The BMI, treatment regimens, type of infertility, endometrium, and timing insemination have no significant prognostic value. CONCLUSION: Apart from the number of treatment cycles, somking, and female age, no other factors had prognostic value. More studies and samples are necessary to evaluate whether other factors affect conception.


Assuntos
Infertilidade Feminina/etiologia , Inseminação Artificial/estatística & dados numéricos , Adulto , Distribuição de Qui-Quadrado , Feminino , Humanos , Infertilidade Feminina/diagnóstico , Inseminação Artificial/métodos , Gravidez , Resultado da Gravidez/epidemiologia , Estudos Retrospectivos , Fatores de Tempo
11.
J Int Med Res ; 49(5): 3000605211018600, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34038202

RESUMO

OBJECTIVE: To evaluate the effects of body mass index (BMI) in patients with polycystic ovary syndrome (PCOS) undergoing controlled ovarian stimulation (COS) with intrauterine insemination (IUI). METHODS: This retrospective study evaluated couples with PCOS undergoing COS and IUI. The relationship between cumulative IUI pregnancy outcomes and BMI, treatment cycles, treatment schemes, number of dominant follicles, endometrial thickness, infertility duration and type of infertility was analysed. RESULTS: The study evaluated 831 IUI cycles in 451 couples with PCOS. Compared with normoweight women, overweight and obese women required more human menopausal gonadotropin (hMG) doses and more days of COS. Gestational diabetes mellitus occurred more frequently in the obese group than in the other BMI groups. The clinical pregnancy and live birth rates in the hMG, clomiphene citrate (CC) + hMG and letrozole (LE) + hMG groups were significantly higher than those in the CC and LE groups. The clinical pregnancy rate was higher in the secondary infertility group compared with the primary infertility group. CONCLUSION: Obese women might require more hMG doses and more days of COS to overcome the effects of weight. As BMI increases, the incidence of gestational diabetes might also increase. The number of cycles and type of infertility may have a predictive value for pregnancy outcomes.


Assuntos
Infertilidade Feminina , Síndrome do Ovário Policístico , Feminino , Fármacos para a Fertilidade Feminina , Humanos , Inseminação , Indução da Ovulação , Síndrome do Ovário Policístico/complicações , Gravidez , Taxa de Gravidez , Estudos Retrospectivos
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