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1.
Environ Res ; 247: 118279, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38246301

ABSTRACT

The presence of hazardous dyes in wastewater poses significant threats to both ecosystems and the natural environment. Conventional methods for treating dye-contaminated water have several limitations, including high costs and complex operational processes. This study investigated a sustainable bio-sorbent composite derived from the Capparis decidua plant and eggshells, and evaluated its effectiveness in removing anionic dyes namely tartrazine (E-102), methyl orange (MO), and their mixed system. The research examines the influence of initial concentration, contact time, pH, adsorbent dosage, and temperature on the adsorption properties of anionic dyes. Optimal removal of tartrazine (E-102), methyl orange (MO), and their mixed system was achieved at a pH of 3. The equilibrium was achieved at 80 min for MO and mixed systems, and 100 min for E-102. The adsorption process showed an exothermic nature, indicating reduced capacity with increasing temperature, consistent with heat release during adsorption. Positive entropy values indicated increased disorder at the solid-liquid interface, attributed to molecular rearrangements and interactions between dye molecules and the adsorbent. Isotherm analysis using Langmuir, Freundlich, Temkin, and Redlich-Peterson models revealed that the Langmuir model best fit the experimental data. The maximum adsorption capacities of 50.97 mg/g, 52.24 mg/g, and 56.23 mg/g were achieved for E-102, MO, and the mixed system under optimized conditions, respectively. The pseudo-second-order kinetic model demonstrated the best fit, indicating that adsorption occurs through physical and chemical interactions such as electrostatic attraction, pore filling, and hydrogen bonding. Hence, the developed bio-sorbent could be a sustainable and cost-effective solution for the treatment of anionic dyes from industrial effluents.


Subject(s)
Azo Compounds , Capparis , Water Pollutants, Chemical , Water Purification , Animals , Female , Coloring Agents/chemistry , Tartrazine , Egg Shell/chemistry , Ecosystem , Water Purification/methods , Indicators and Reagents , Decidua/chemistry , Adsorption , Kinetics , Hydrogen-Ion Concentration , Water Pollutants, Chemical/analysis
2.
Environ Res ; 229: 115955, 2023 07 15.
Article in English | MEDLINE | ID: mdl-37119845

ABSTRACT

Placenta mediates the transfer of nutrients, oxygen and drugs from mother to fetus. It is constituted by two cellular layers separated by the intervillous space: the outer is in direct contact with maternal blood (decidua placenta), and the inner (villi) directly in contact with the fetus. Environmental contaminants, such as per- and polyfluoroalkyl substances (PFAS) also demonstrated the ability to cross the tissue multiple layers, posing at risk the health of the fetus. The aim of the present study was to analyse the PFAS amount in decidua and villi placenta explants and to study differences in their distribution among the two side of this organ. The determination of 23 PFAS was carried out by liquid chromatography coupled to high-resolution accurate mass spectrometry (LC-HRAM). Our research included women who delivered at term between 2021 and 2022. Our data indicated that all samples contained at least one PFAS, demonstrating the ubiquitarian presence of these compounds in our population. A high occurrence of PFOS, PFOA and PFHxS, followed by PFHxA, PFBS and PFUnA was found. The fluorotelomer 6:2 FTS was also present in more than 40% of samples and this represent the first data on placenta explants. Mean and median PFAS values for decidual explants were 0.5 ng/g and 0.4 ng/g (SD 0.3), while for villi explants mean and median values were 0.6 ng/g and 0.4 ng/g (SD 0.4). A different pattern of accumulation was observed between villi and decidual explants for PFOS, PFOA and PFUnA (villi > decidua) and PFHxA, PFHxS, PFBS and 6:2 FTS (decidua > villi). Even if the mechanism of this selectively accumuation is not yet understood, molecular degree of ionization and its lipophilicity could at least in part explain this difference. This study expands the limited data describing PFAS levels in the placenta and pose attention on PFAS exposure during pregnancy.


Subject(s)
Alkanesulfonic Acids , Environmental Pollutants , Fluorocarbons , Pregnancy , Humans , Female , Placenta/chemistry , Mothers , Decidua/chemistry , Alkanesulfonic Acids/analysis , Environmental Pollutants/analysis
3.
BMC Pharmacol Toxicol ; 23(1): 55, 2022 07 23.
Article in English | MEDLINE | ID: mdl-35869506

ABSTRACT

BACKGROUND: As a progesterone receptor antagonist, mifepristone combined with misoprostol is widely used to terminate early pregnancy in clinical practice. It has also been reported that mifepristone may cause cell death in decidual cells and result in hemorrhage of the decidua and insufficient blood supply. However, little is known about the histological effects of mifepristone on human decidua and chorion. METHODS: Histological and subcellular structural changes of decidua and chorionic villi from women taking mifepristone at early pregnancy times were examined by Hematoxylin and eosin (H&E) staining and transmission Electron microscope. The expression of apoptosis-related proteins Bax/Bcl-2 was examined by immunohistochemistry. RESULTS: After 48 h of mifepristone administration, the decidua tissue and chorionic villus structures were altered in women within 39-49 days of gestation and displayed varying degrees of degeneration and necrosis-like features. Apoptotic events were observed in the decidua and chorionic villi of early pregnancy, and mifepristone treatment significantly increases the number of apoptotic cells. The increased apoptotic events were concomitant with the increased expression of Bax and decreased expression of Bcl-2. CONCLUSION: This study provides evidence that mifepristone induces histological and subcellular changes in decidua and chorionic villi. Mifepristone modulates the relative ratio of Bax/Bcl-2 and the increased apoptosis contributes to the pregnancy termination at early stage of pregnancy.


Subject(s)
Mifepristone , Misoprostol , Proto-Oncogene Proteins c-bcl-2/metabolism , bcl-2-Associated X Protein/metabolism , Chorionic Villi/chemistry , Chorionic Villi/metabolism , Chorionic Villi/pathology , Decidua/chemistry , Decidua/metabolism , Female , Humans , Mifepristone/analysis , Mifepristone/metabolism , Mifepristone/pharmacology , Misoprostol/analysis , Misoprostol/metabolism , Misoprostol/pharmacology , Pregnancy
4.
J Obstet Gynaecol ; 39(8): 1117-1122, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31195902

ABSTRACT

There is conflicting literature on whether the levonorgestrel-releasing intrauterine system (LNG-IUS; Mirena®) induces decidualisation in the tamoxifen-treated endometrium. The expression of the decidualisation marker IGFBP-1 was measured using immunohistochemistry in endometrial biopsies and in serum (using ELISA) of 20 postmenopausal women at the start of tamoxifen-treatment for breast cancer. Ten women were then fitted with LNG-IUS and the other ten received tamoxifen-treatment only and acted as controls. Samples were taken at baseline and after 12 months. At baseline, all endometrial samples were negative for IGFBP-1 and at 12 months, IGFBP-1 was only expressed in the endometria of women fitted with the LNG-IUS, confirming the observed histological features of decidualisation. By contrast, serum IGFBP-1 concentrations were increased by tamoxifen, but not in the group receiving LNG-IUS. In conclusion, tamoxifen induces a rise in serum IGFBP-1 suggesting a systemic, possibly hepatic effect, whilst LNG abrogates this in both the liver and endometrium. Impact statement What is already known on this subject? Previous reports of the use of LNG-IUS in women on tamoxifen have provided conflicting evidence as to whether the endometrium exhibited decidualisation or not. These reports were however based solely on histological examination and lacked supporting biochemical data. What do the results of this study add? After 12 months of treatment with LNG-IUS, the endometria of women on tamoxifen show histological features of decidualisation and the presence of the decidualisation marker IGFBP-1, suggesting that levonorgestrel protects the tamoxifen-treated uterus from additional pathology by causing decidualisation. Serum levels of IGFBP-1 were expected to be a reflection of uterine production, but contrary to expectations, higher levels were identified in women on tamoxifen alone. These data suggest that an inhibition of tamoxifen-induced serum IGFBP-1 production (possibly from a hepatic source) by LNG-IUS occurred and indicates independent systemic effects of both drugs in post menopausal breast cancer patients. What are the implications of these findings for clinical practice and/or further research? This research demonstrated a mechanism for endometrial protection in women on tamoxifen. It also alerts clinicians to the fact that both tamoxifen and LNG-IUS exert systemic effects in this patient group.


Subject(s)
Breast Neoplasms/drug therapy , Decidua/drug effects , Endometrium/drug effects , Intrauterine Devices, Medicated , Levonorgestrel/administration & dosage , Tamoxifen/therapeutic use , Aged , Biomarkers/analysis , Decidua/chemistry , Decidua/physiology , Endometrium/pathology , Endometrium/physiology , Female , Humans , Immunohistochemistry , Insulin-Like Growth Factor Binding Protein 1/analysis , Insulin-Like Growth Factor Binding Protein 1/blood , Middle Aged , Postmenopause
5.
Reprod Sci ; 26(6): 774-784, 2019 06.
Article in English | MEDLINE | ID: mdl-30213224

ABSTRACT

During decidualization, endometrial stromal cells differentiate into a secretory phenotype to modulate the uterine microenvironment and promote embryo implantation. This highly metabolic process relies on ovarian steroid receptors and glucose transporters. Canonical Notch signaling is mediated by the transcription factor Recombination Signal Binding Protein for Immunoglobulin Kappa J Region (RBPJ). Loss of RBPJ in the mouse uterus (Pgrcre/+Rbpjflox/flox; Rbpj c-KO) results in subfertility in part due to an abnormal uterine-embryonic axis during implantation and, as described herein, decidualization failure. Induced in vivo decidualization in Rbpj c-KO mice was impaired with the downregulation of decidual markers and decreased progesterone receptor (Pgr) signaling. Consistent with in vivo mouse data, RBPJ knockdown during in vitro Human uterine fibroblast (HuF) cell decidualization results in the reduced expression of decidual marker genes along with PGR. Expression of the glucose transporter, SLC2A1, was decreased in the RBPJ-silenced HuF cells, which corresponded to decreased Slc2a1 in the secondary decidual zone of Rbpj c-KO mouse uteri. Exogenous administration of pyruvate, which bypasses the need for glucose, rescues PRL expression in RBPJ-deficient HuF cells. In summary, Notch signaling through RBPJ controls both ovarian steroid receptor PGR and glucose transporter SLC2A1 expression during decidualization, and this dysregulation likely contributes to embryo implantation failure.


Subject(s)
Decidua/physiology , Gene Expression Regulation/physiology , Glucose Transporter Type 1/genetics , Immunoglobulin J Recombination Signal Sequence-Binding Protein/physiology , Receptors, Progesterone/genetics , Animals , Cell Line , Decidua/chemistry , Female , Fibroblasts , Glucose Transporter Type 1/analysis , Humans , Immunoglobulin J Recombination Signal Sequence-Binding Protein/deficiency , Immunoglobulin J Recombination Signal Sequence-Binding Protein/genetics , Mice , Mice, Knockout , Pyruvic Acid/pharmacology , RNA, Small Interfering/genetics , Receptors, Progesterone/metabolism , Signal Transduction/physiology , Uterus/cytology
6.
J Biomed Mater Res A ; 107(1): 232-242, 2019 01.
Article in English | MEDLINE | ID: mdl-30378728

ABSTRACT

Coatings produced from extracellular matrixes (ECMs) have emerged as promising surfaces for the improved ex vivo expansion of mesenchymal stem cells (MSCs). However, identifying a readily available source of ECM to generate these coatings is currently the bottleneck of this technology. In this study, we assessed if ECM coatings derived from decellularized fetal membranes were a suitable substrate for MSC expansion. We separated and decellularized the two main components of the fetal membranes, the amnion and the chorion. Characterization of the decellularized membranes revealed that each membrane component has a distinct composition, implying that coatings produced from these materials would have unique biological properties. The membranes were processed further to produce solubilized forms of the decellularized amniotic membrane (s-dAM) and decellularized chorionic membrane (s-dCM). On s-dAM coatings decidual MSCs (DMSC) were more proliferative than those cultured on tissue culture plastic alone or on Matrigel coatings; were smaller in size (a measure of MSC potency); exhibited greater adipogenic differentiation capacity; and improved osteogenic capacity. Additionally, long term culture studies showed late passage DMSCs (passage 8) cultured on s-dAM showed a decrease in cell diameter over three passages. These data support the use of s-dAM as a substrate for improved MSC expansion. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 232-242, 2019.


Subject(s)
Cell Culture Techniques , Cell Proliferation , Decidua/chemistry , Extracellular Matrix/chemistry , Mesenchymal Stem Cells/metabolism , Female , Humans , Mesenchymal Stem Cells/cytology , Pregnancy
7.
Adv Anat Pathol ; 25(5): 369-371, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29727323

ABSTRACT

Peritoneal lipofuscinosis is a very rarely recognized condition occurring during pregnancy characterized by brown pigmentation of the omentum and peritoneum, a decidual reaction and benign mesothelial cells. The iron negative pigment, which is likely to be confused with hemosiderin in the hematoxylin and eosin stain, is lipofuscin. The seminar case, apparently the third published, arose in a 37-year-old woman who presented in October 2015 at 24 weeks pregnancy with abdominal pain. Investigations revealed a ruptured left ovarian cyst and rising serum carcinoembryonic antige levels. At laparotomy, there was no free intraperitoneal blood but the omentum and uterine serosa were black. Histology showed lipofuscinosis and a decidual reaction. The patient delivered a normal baby in February 2016 and was clinically well after delivery. A left ovarian endometriotic cyst was removed in February 2017. The patient made a good recovery with no clinically apparent symptoms from the liposuscinosis. We postulate that the endometriotic cyst had ruptured and released blood into the peritoneal cavity in 2015. The iron from the red cells breakdown was then rapidly resorbed because of the pregnancy requirements for iron, leaving lipofuscin in peritoneal macrophages.


Subject(s)
Decidua/pathology , Lipofuscin/analysis , Omentum/pathology , Ovarian Cysts/pathology , Peritoneal Diseases/pathology , Peritoneum/pathology , Pregnancy Complications/pathology , Adult , Biopsy , Decidua/chemistry , Decidua/surgery , Female , Humans , Omentum/chemistry , Omentum/surgery , Ovarian Cysts/blood , Ovarian Cysts/surgery , Peritoneal Diseases/blood , Peritoneal Diseases/surgery , Peritoneum/chemistry , Peritoneum/surgery , Pregnancy , Pregnancy Complications/blood , Pregnancy Complications/surgery , Rupture, Spontaneous
8.
Braz J Med Biol Res ; 50(11): e6527, 2017 Sep 12.
Article in English | MEDLINE | ID: mdl-28902929

ABSTRACT

Immunological mechanisms have been proposed to underlie the pathogenesis of recurrent spontaneous abortion (RSA). Vitamin D has a potent immunomodulatory effect, which may affect pregnancy outcome. The objective of this study was to investigate 25-hydroxyvitamin D [25(OH) D] concentration and vitamin D receptor (VDR) expression in the decidual tissues of RSA patients. Thirty women with RSA (RSA group) and thirty women undergoing elective abortion (control group) were recruited during 2016 from gynecology outpatient clinics. We measured 25(OH) D, interleukin (IL)-17, IL-23, transforming growth factor ß (TGF-ß), VDR and 1-α-hydroxylase (CYP27B1) in decidual tissues collected during the abortion procedure. In the RSA group, 25(OH) D and TGF-ß were significantly decreased while IL-17 and IL-23 were significantly increased compared with the control group. VDR expression was significantly decreased in the RSA group compared with the control group. Logistic regression analysis showed a significant negative correlation between 25(OH) D in decidual tissues and RSA. These results indicated that vitamin D concentrations in the decidua are associated with inflammatory cytokine production, suggesting that vitamin D and VDR may play a role in the etiology of RSA.


Subject(s)
25-Hydroxyvitamin D3 1-alpha-Hydroxylase/analysis , Abortion, Habitual/metabolism , Decidua/chemistry , Receptors, Calcitriol/analysis , Vitamin D/analogs & derivatives , 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/metabolism , Abortion, Habitual/etiology , Adult , Female , Humans , Interleukin-17/analysis , Interleukin-23/analysis , Logistic Models , Pregnancy , Pregnancy Trimester, Third , Receptors, Calcitriol/metabolism , Risk Factors , Statistics, Nonparametric , Transforming Growth Factor beta/analysis , Vitamin D/analysis , Vitamin D/metabolism , Vitamin D Deficiency/complications , Young Adult
9.
Reprod Domest Anim ; 52 Suppl 2: 137-147, 2017 Apr.
Article in English | MEDLINE | ID: mdl-27862405

ABSTRACT

The apparent lack of classical mechanisms for maternal recognition of pregnancy is one of the most intriguing features of canine reproduction. Consequently, similar levels of circulating luteal steroids are observed in pregnant and non-pregnant dogs. However, the early pre-implantation canine embryo locally modulates uterine responses to its presence, facilitating the successful onset of pregnancy. As a part of this interaction, the canine uterus undergoes a species-specific decidualization. Maternal stroma-derived decidual cells develop, the only cells of the canine placenta expressing progesterone receptor (PGR). There exists an acute need for an in vitro stable cell line model for canine decidualization. Therefore, herein our goal was to establish, immortalize and characterize such a cell line. We immortalized three monolayer dog uterine stromal (DUS) cell lines by stably transfecting them with SV40Tag oncogene. Cells retained their mesenchymal character for over 30 passages, as evidenced by VIMENTIN staining. Genomic incorporation of the SV40Tag protein was confirmed by immunofluorescence and Western blot analyses. Cells submitted to a classical in vitro decidualization protocol (N6,2'-O-dibutyryladenosine-3',5'-cyclic monophosphate) revealed upregulated gene levels of selected major decidualization markers (e.g. PRLR, PGR, IGF1, PTGES). Additionally, the basic decidualization capability of PGE2 was demonstrated, revealing increased levels of, for example, PGR and PRLR gene expression, thereby implying its involvement in the progesterone-dependent decidualization in the canine uterus. In summary, our in vitro model with immortalized DUS cell line could serve as an ideal and unique model to study the underlying molecular and endocrine mechanisms of canine decidualization.


Subject(s)
Decidua/cytology , Decidua/physiology , Dogs , Stromal Cells/physiology , Uterus/physiology , Animals , Cell Line, Transformed , Decidua/chemistry , Dinoprostone/pharmacology , Embryo Implantation , Female , Gene Expression , Gestational Age , Placenta/cytology , Pregnancy , Receptors, Progesterone/analysis , Receptors, Progesterone/genetics , Receptors, Prolactin/genetics , Species Specificity , Uterus/cytology
10.
Braz. j. med. biol. res ; 50(11): e6527, 2017. graf
Article in English | LILACS | ID: biblio-888953

ABSTRACT

Immunological mechanisms have been proposed to underlie the pathogenesis of recurrent spontaneous abortion (RSA). Vitamin D has a potent immunomodulatory effect, which may affect pregnancy outcome. The objective of this study was to investigate 25-hydroxyvitamin D [25(OH) D] concentration and vitamin D receptor (VDR) expression in the decidual tissues of RSA patients. Thirty women with RSA (RSA group) and thirty women undergoing elective abortion (control group) were recruited during 2016 from gynecology outpatient clinics. We measured 25(OH) D, interleukin (IL)-17, IL-23, transforming growth factor β (TGF-β), VDR and 1-α-hydroxylase (CYP27B1) in decidual tissues collected during the abortion procedure. In the RSA group, 25(OH) D and TGF-β were significantly decreased while IL-17 and IL-23 were significantly increased compared with the control group. VDR expression was significantly decreased in the RSA group compared with the control group. Logistic regression analysis showed a significant negative correlation between 25(OH) D in decidual tissues and RSA. These results indicated that vitamin D concentrations in the decidua are associated with inflammatory cytokine production, suggesting that vitamin D and VDR may play a role in the etiology of RSA.


Subject(s)
Humans , Female , Pregnancy , Adult , Young Adult , Vitamin D/analogs & derivatives , Abortion, Habitual/metabolism , Receptors, Calcitriol/analysis , Decidua/chemistry , 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/analysis , Pregnancy Trimester, Third , Vitamin D/analysis , Vitamin D/metabolism , Vitamin D Deficiency/complications , Logistic Models , Risk Factors , Abortion, Habitual/etiology , Transforming Growth Factor beta/analysis , Receptors, Calcitriol/metabolism , Statistics, Nonparametric , Interleukin-17/analysis , Interleukin-23/analysis , 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/metabolism
11.
Retrovirology ; 13(1): 39, 2016 06 06.
Article in English | MEDLINE | ID: mdl-27267272

ABSTRACT

BACKGROUND: During the first trimester of pregnancy, HIV-1 in utero transmission is rare despite the permissivity of the placenta and the decidua (the uterine mucosa during pregnancy) to infection. In the decidua from the first trimester of pregnancy, macrophages (dMs) are the HIV-1 main target cells. Decidual natural killer (dNK) cells account for 70 % of decidual leukocytes. They display distinct phenotype and functions compared to peripheral NK cells. At the periphery, NK cells are involved in the control of HIV-1 infection. In this study, we investigate whether human decidual natural killer (dNK) cells control dM HIV-1 infection. RESULTS: Autologous cocultures of infected dMs with dNK cells reveal that dNK cells strongly inhibit dM HIV-1 infection. The addition of dNK cells to dMs at different times after infection suggests that the control occurs before the complete establishment of the infection. Double chamber cocultures show that cellular contacts are necessary for an optimal control of infection. Nevertheless, soluble factors secreted by dMs and dNK cells in double chamber cocultures partially inhibit dM HIV-1 infection, indicating that soluble factors have also a role in the control of infection. IFN-γ secretion is increased in infected and uninfected cocultures. We show that IFN-γ is involved in the control of dM HIV-1 infection by dNK cells. CONCLUSIONS: These results demonstrate that human dNK cells inhibit efficiently HIV-1 infection in dMs in vitro, and highlight the role of innate immune determinants in the control of HIV-1 transmission.


Subject(s)
Decidua/cytology , Decidua/immunology , HIV-1/physiology , Killer Cells, Natural/immunology , Macrophages/virology , Cells, Cultured , Coculture Techniques , Culture Media/chemistry , Decidua/chemistry , Female , HIV Infections/transmission , Humans , Infectious Disease Transmission, Vertical , Interferon-gamma/metabolism , Pregnancy , Pregnancy Trimester, First
12.
Pregnancy Hypertens ; 6(1): 30-7, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26955769

ABSTRACT

The bradykinin type 2 receptor (B2R), main effector of the pleiotropic kallikrein-kinin system (KKS), has been localized in the key sites related to placentation in human, rat and guinea pig utero-placental units. The present study was directed to characterize the content, the cellular and subcellular localization of B2R in the villi and basal plate of placentas from normal and preeclamptic pregnancies by means of western blotting, immunohistochemistry and immunoelectron microscopy. The protein content of B2R was demonstrated in both placental zones. The villous placenta of normal and preeclamptic pregnancies expressed B2R in syncytiotrophoblast and fetal endothelium; the basal plate displayed B2R in extravillous trophoblasts and decidual cells. Lastly, immunogold electron microscopy revealed B2R in fetal endothelium, syncytiotrophoblast, extravillous cytotrophoblasts and decidual cells; in all cell types the receptor was mainly located in the cytosol and nucleus. The protein content of placental homogenates and the immunoreactivity in the different cells types did not differ between both study groups; however the abundance of nuclear immunogold B2R positive beads in extravillous trophoblasts was greater in the normal than in the preeclamptic placentas. The purpose of describing nuclear B2R in the utero-placental unit, and its increment in normal extravillous trophoblasts, is to stimulate the study of the functional pathways that may be relevant to understand the local role of the B2R in normal and preeclamptic gestation.


Subject(s)
Cell Nucleus/chemistry , Placenta/chemistry , Pre-Eclampsia/metabolism , Receptor, Bradykinin B2/analysis , Uterus/chemistry , Adult , Biomarkers/analysis , Blotting, Western , Case-Control Studies , Cell Nucleus/ultrastructure , Chorionic Villi/chemistry , Decidua/chemistry , Endothelial Cells/chemistry , Female , Humans , Immunohistochemistry , Microscopy, Electron , Placenta/ultrastructure , Pre-Eclampsia/diagnosis , Pregnancy , Trophoblasts/chemistry , Uterus/ultrastructure , Young Adult
13.
Arch Gynecol Obstet ; 293(5): 1125-35, 2016 May.
Article in English | MEDLINE | ID: mdl-26879955

ABSTRACT

PURPOSE: MicroRNAs (miRNAs) are small non-coding RNA molecules that play critical roles in post-transcriptional gene expression regulation. The aim of this study was to identify differentially expressed miRNAs in decidua and villus of recurrent miscarriage (RM) patients. METHODS: Participants were recruited at the outpatient Department of Gynecology and Obstetrics, The Second Hospital of Tianjin Medical University, China. Decidua and villus tissues were collected by curettage from recruited RM patients and normal pregnant women with their informed consent. MiRNAs expression profiles in decidua or villus were respectively determined by the deep-sequencing analysis. The predicated target genes of these differentially expressed miRNAs were analyzed by miRWalk. The differential expressions of four miRNAs in decidua and four miRNAs in villus between the six pairs of RM patients and normal pregnant women were confirmed by qRT-PCR analysis. The expression patterns of two predicated target genes, Bcl-2 and Pten, in the same six pairs of decidual or villus tissues were detected by Western blotting analysis, respectively. RESULTS: Totally 18 RM patients and 15 normal pregnant women were recruited. Thirty-two miRNAs in decidua and four miRNAs in villus of RM patients were screened out to be significantly up-regulated compared to that of normal pregnant women, and five miRNAs in villus of RM patients were screened out to be remarkably down-regulated compared to that of normal pregnant women (P value < 0.05 and Fold change >2). These differentially expressed miRNAs were predicted to target a large number of genes that involved in cell apoptosis, p53 signaling pathway, cell cycle and other cellular bio-functions. Differential expressions of hsa-miR-516a-5p, -517a-3p, -519a-3p and -519d in decidua, as well as hsa-miR-1, -372, -100-5p and -146a-5p in villus, were validated by qRT-PCR analysis. In the decidual of RM patients, expression of hsa-miR-516a-5p, -517a-3p, -519a-3p and -519d were significantly up-regulated compared to normal pregnancy. In the villi of RM patients, expression of hsa-miR-100 and -146a-5p were significantly higher, while hsa-miR-1 and -372 were significantly lower compared to normal pregnancy. Furthermore, the expression of Bcl-2 and Pten, a predicated target gene of hsa-miR-1 or hsa-miR-372 respectively, was significantly up-regulated in the villi of RM patients. CONCLUSIONS: These data suggested that the pathogenic process of RM might be associated with the alteration of miRNAs expression profiles in decidua and villus. Especially, the aberrant placental expression of hsa-miR-1 and -372 might be involved in the progression of RM, but need to be further investigated by larger studies in the future.


Subject(s)
Abortion, Habitual/genetics , Chorionic Villi/metabolism , Decidua/metabolism , Gene Expression Profiling/methods , MicroRNAs/analysis , Placenta/chemistry , Adult , China , Chorionic Villi/chemistry , Decidua/chemistry , Down-Regulation , Female , Gene Expression Regulation , Genetic Markers , Humans , Placenta/pathology , Placenta/physiopathology , Pregnancy , Up-Regulation
14.
Contraception ; 93(4): 323-330, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26707996

ABSTRACT

OBJECTIVE: To evaluate if letrozole-induced suppression of estradiol reduces progesterone receptor expression and apoptosis in the first-trimester placenta. STUDY DESIGN: We performed a double-blinded, randomized, placebo-controlled trial. We randomized 20 women requesting first-trimester abortion with gestation up to 63 days to receive either letrozole 10 mg daily or placebo pretreatment for 7 days before administrating 400 mcg of vaginal misoprostol followed by suction abortion. We collected the placental and decidual tissues on which we performed immunohistochemical staining for progesterone receptor and apoptotic markers (active caspase 3, caspase 3, Bcl2, CD95, fas ligand) and determined H-scores of each based on the intensities of staining. We performed terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay for apoptosis in the samples of four women to confirm the findings from apoptotic markers. RESULTS: We excluded one woman in the letrozole group from the analysis because she had passage of abortus after taking letrozole, leaving 19 women (9 in the letrozole group, 10 in the placebo group) for analysis. There was no significant difference in the H-scorings of progesterone receptor and apoptotic markers, as well as proportion of apoptotic cells on TUNEL assay between the two groups. The H-scores for the progesterone receptor were 8.17 ± 2.67 (mean ± SD) in the letrozole group and 9.01 ± 2.82 in the placebo group (p=0.36). CONCLUSION: We did not detect a difference in the expression of progesterone receptor and apoptotic markers in placental and decidual tissues after letrozole pretreatment for 7 days in first-trimester abortion. IMPLICATIONS: We did not confirm the hypothesis that letrozole reduces progesterone receptor expression and induces apoptosis in the first-trimester placenta. Further studies are required to allow better understanding of the mechanism by which estrogen suppression following the use of letrozole can lead to improved abortion rate in the first trimester.


Subject(s)
Abortion, Induced/methods , Apoptosis/drug effects , Decidua/chemistry , Nitriles/administration & dosage , Placenta/chemistry , Receptors, Progesterone/analysis , Triazoles/administration & dosage , Abortifacient Agents, Nonsteroidal , Adult , Biomarkers/analysis , Double-Blind Method , Female , Humans , Immunohistochemistry , In Situ Nick-End Labeling , Letrozole , Misoprostol/administration & dosage , Placebos , Pregnancy , Pregnancy Trimester, First
15.
PLoS One ; 10(12): e0145968, 2015.
Article in English | MEDLINE | ID: mdl-26717016

ABSTRACT

Preeclampsia (PE) is a multisystem disorder unique to Homo sapiens that is known to cause maternal and perinatal mortality and morbidity. Between 5-7% of all pregnancies are affected by PE and it is responsible for approximately 50,000 maternal deaths annually. The pathogenesis of PE remains poorly understood. However, the results of this study indicated that insufficient decidualization plays a significant role. NR5A1 and NR5A2 are orphan members of the Ftz-F1 subfamily of nuclear receptors and are involved in mammal follicular development, female reproduction, steroidogenesis, and decidualization. The expression of NR5A1 and NR5A2 in the human decidua and their functions during decidualization were investigated using in vitro cultured cells by real-time PCR, immunohistochemistry, western blotting, and siRNA techniques. The results demonstrated that the levels of NR5A2 mRNA and protein in the decidual tissues of women with PE were lower than those of normal pregnant women. However, the levels of NR5A1 mRNA and protein did not significantly differ between groups. The expression of NR5A2 was upregulated after in vitro decidualization, but the expression of NR5A1 remained low and showed no difference compared with that of the control cells. Knocking down of NR5A2 in human endometrial stromal cells (hESC) resulted in a significant reduction in their expression of decidualization markers (IGFBP1 and PRL) and signaling pathway molecules (WNT4 and BMP2) (P < 0.05). From these data, we concluded that NR5A2 is pivotal for the decidualization of decidual tissues and cultured human endometrial stromal cells. Disorders of the endometrium in decidual tissues may be associated with the abnormal decidualization thought to cause PE.


Subject(s)
Decidua/metabolism , Pre-Eclampsia/etiology , Receptors, Cytoplasmic and Nuclear/physiology , Adult , Blotting, Western , Case-Control Studies , Decidua/chemistry , Decidua/physiology , Endometrium/cytology , Female , Gene Knockdown Techniques , Humans , In Vitro Techniques , Pregnancy , Real-Time Polymerase Chain Reaction , Receptors, Cytoplasmic and Nuclear/analysis , Receptors, Cytoplasmic and Nuclear/metabolism , Steroidogenic Factor 1/analysis , Steroidogenic Factor 1/physiology
16.
Anal Bioanal Chem ; 407(28): 8543-56, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26350236

ABSTRACT

Tissue proteomics has relied heavily on two-dimensional gel electrophoresis, for protein separation and quantification, then single protein isolation, trypsin digestion, and mass spectrometric protein identification. Such methods are predominantly used for study of high-abundance, full-length proteins. Tissue peptidomics has recently been developed but is still used to study the most highly abundant species, often resulting in observation and identification of dozens of peptides only. Tissue lipidomics is likewise new, and reported studies are limited. We have developed an "omics" approach that enables over 7,000 low-molecular-weight, low-abundance species to be surveyed and have applied this to human placental tissue. Because the placenta is believed to be involved in complications of pregnancy, its proteomic evaluation is of substantial interest. In previous research on the placental proteome, abundant, high-molecular-weight proteins have been studied. Application of large-scale, global proteomics or peptidomics to the placenta have been limited, and would be challenging owing to the anatomic complexity and broad concentration range of proteins in this tissue. In our approach, involving protein depletion, capillary liquid chromatography, and tandem mass spectrometry, we attempted to identify molecular differences between two regions of the same placenta with only slightly different cellular composition. Our analysis revealed 16 species with statistically significant differences between the two regions. Tandem mass spectrometry enabled successful sequencing, or otherwise enabled chemical characterization, of twelve of these. The successful discovery and identification of regional differences between the expression of low-abundance, low-molecular weight biomolecules reveals the potential of our approach.


Subject(s)
Chorionic Villi/chemistry , Chromatography, Liquid/methods , Decidua/chemistry , Peptides/isolation & purification , Phospholipids/isolation & purification , Proteome/isolation & purification , Amino Acid Sequence , Chorionic Villi/metabolism , Chromatography, Liquid/instrumentation , Decidua/metabolism , Female , Gene Expression , Gene Expression Profiling , Humans , Molecular Sequence Data , Molecular Weight , Pregnancy , Proteomics/instrumentation , Proteomics/methods , Tandem Mass Spectrometry
17.
Histochem Cell Biol ; 144(6): 571-85, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26340953

ABSTRACT

Implantation of the mammalian embryo requires profound endometrial changes for successful pregnancy, including epithelial-mesenchymal transition of the luminal epithelium and stromal-epithelial transition of the stromal cells resulting in decidualization. Claudins (Cldn) determine the variability in tight junction paracellular permeability and may play a role during these epithelial and decidual changes. We here localized Cldn3, Cldn7 and Cldn10 proteins in the different compartments of murine endometrium up to day 8.5 of pregnancy (dpc) as well as in human endometrium and first trimester decidua. In murine estrous endometrium, luminal and glandular epithelium exhibited Cldn3 and Cldn7, whereas Cldn10 was only detectable in glandular epithelium. At 4.5 dpc, Cldn3 protein shifted to an apical localization, whereas Cldn7 vanished in the epithelium of the implantation chamber. At this stage, there was no stromal signal for Cldn3 and Cldn7, but a strong induction of Cldn10 in the primary decidual zone. Cldn3 proteins emerged at 5.5 dpc spreading considerably from 6.5 dpc onward in the endothelial cells of the decidual blood sinusoids and in the decidual cells of the compact antimesometrial region. In addition to Cldn3, Cldn10 was identified in human endometrial epithelia. Both proteins were not detected in human first trimester decidual cells. Cldn3 was shown in murine trophoblast giant cells as well as in human extravillous trophoblast cells and thus may have an impact on trophoblast invasion in both species. We here showed a specific claudin signature during early decidualization pointing to a role in decidual angiogenesis and regulation of trophoblast invasion.


Subject(s)
Claudin-3/metabolism , Claudins/metabolism , Decidua/metabolism , Pregnancy, Animal/metabolism , Trophoblasts/metabolism , Animals , Claudin-3/analysis , Claudins/analysis , Decidua/chemistry , Decidua/cytology , Endometrium/chemistry , Endometrium/metabolism , Female , Humans , Male , Mice , Mice, Inbred C57BL , Pregnancy , Trophoblasts/chemistry , Trophoblasts/cytology
18.
BMC Pregnancy Childbirth ; 14: 241, 2014 Jul 22.
Article in English | MEDLINE | ID: mdl-25048443

ABSTRACT

BACKGROUND: Elucidation of the biochemical pathways involved in activation of preterm and term human labour would facilitate the development of effective management and inform judgements regarding the necessity for preterm tocolysis and post-term induction. Prostaglandins act at all stages of human reproduction, and are potentially activators of labour. METHODS: Expression of 15 genes involved in prostaglandin synthesis, transport and degradation was measured by qPCR using tissue samples from human placenta, amnion and choriodecidua at preterm and full-term vaginal and caesarean delivery. Cellular localisation of eight prostaglandin pathway proteins was determined by immunohistochemistry. RESULTS: Expression of prostaglandin pathway genes was differentially affected by factors including gestational age at delivery, and the incidence and duration of labour. Chorioamnionitis/deciduitis was associated with upregulation of PTGS2 (prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)), along with the inflammatory genes IL8 (interleukin 8), S100A8 (S100 calcium binding protein A8) and TLR2 (toll-like receptor 2), in amnion and choriodecidua, and with downregulation of CBR1 (carbonyl reductase 1) and HPGD (hydroxyprostaglandin dehydrogenase 15-(NAD)) in choriodecidua. Protein localisation differed greatly between the various maternal and fetal cell types. CONCLUSIONS: Preterm and term labour are associated with distinct prostaglandin pathway expression profiles; inflammation provokes specific changes, unrelated to the presence of labour; spontaneous and induced term labour are indistinguishable.


Subject(s)
Gene Expression , Labor, Obstetric/genetics , Obstetric Labor, Premature/genetics , Prostaglandins/analysis , Prostaglandins/genetics , Signal Transduction/genetics , 3-Hydroxysteroid Dehydrogenases/analysis , 3-Hydroxysteroid Dehydrogenases/genetics , Adult , Alcohol Oxidoreductases/analysis , Alcohol Oxidoreductases/genetics , Aldehyde Reductase/analysis , Aldehyde Reductase/genetics , Aldo-Keto Reductase Family 1 Member C3 , Amnion/chemistry , Calgranulin A/analysis , Calgranulin A/genetics , Chorioamnionitis/genetics , Chorion/chemistry , Cyclooxygenase 2/analysis , Cyclooxygenase 2/genetics , Cytochrome P-450 Enzyme System/analysis , Cytochrome P-450 Enzyme System/genetics , Decidua/chemistry , Down-Regulation , Female , Gestational Age , Humans , Hydroxyprostaglandin Dehydrogenases/analysis , Hydroxyprostaglandin Dehydrogenases/genetics , Interleukin-1/analysis , Interleukin-1/genetics , Intramolecular Oxidoreductases/analysis , Intramolecular Oxidoreductases/genetics , Labor, Obstetric/metabolism , Multidrug Resistance-Associated Proteins/analysis , Multidrug Resistance-Associated Proteins/genetics , Obstetric Labor, Premature/metabolism , Organic Anion Transporters/analysis , Organic Anion Transporters/genetics , Placenta/chemistry , Pregnancy , Prostaglandin-E Synthases , Prostaglandins/metabolism , Toll-Like Receptor 2/analysis , Toll-Like Receptor 2/genetics , Up-Regulation , Young Adult
19.
Placenta ; 35(6): 378-85, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24725555

ABSTRACT

INTRODUCTION: Primary infertility, miscarriage, and preeclampsia have been correlated with reduced numbers of regulatory T-cells (Treg) suggesting that decreased extravillous trophoblast (EVT) invasion originates from inadequate EVT tolerance. In contrast increased numbers of Treg-cells may be responsible for over-invasion of EVT. As the maturation status of dendritic cells (DC) influences T-cell behavior (tolerance or immune activation), altered relation between immature and mature DCs may also influence EVT invasion. METHOD: Paraffin-embedded specimens of placenta accreta/increta (Pc; n = 11) and healthy intrauterine pregnancy (IUG; n = 18) were double-stained for cytokeratin and CD45, CD68, CD56, CD20, CD3, or CD8 as well as FoxP3/CD4 and FoxP3/CD8 and single-stained for CD4, CD25, FoxP3, CD209, Dec205 and CD83. Quantification of the leukocyte subpopulations was performed for decidua parietalis and basalis as characterized by cytokeratin-positive EVT. Statistical analysis was performed by using the Mann-Whitney test. RESULT: There were significantly fewer CD4(+) cells in Pc than in IUG. Concerning the Treg-markers, FoxP3(+) cells are significantly increased. CD25(+) cells showed a small non-significant increase in Pc in comparison to IUG. Concerning dendritic cells, immature non-activated CD209(+) DCs were significantly decreased in Pc while immature activated CD205(+) DCs were slightly but non-significantly increased. Mature activated CD83(+) DC were non-significantly decreased in IUG vs Pc. DISCUSSION AND CONCLUSION: The increased number of Treg-cells in Pc suggests significance for these cells in the regulation of trophoblast invasion. Their adequate interaction with other lymphocyte populations (e.g. adequately maturated dendritic cells) may be one mechanism to assure controlled EVT invasion.


Subject(s)
Decidua/immunology , Dendritic Cells/immunology , Placenta Accreta/immunology , T-Lymphocytes, Regulatory/immunology , Adult , Antigens, CD/analysis , Biomarkers/analysis , CD4 Lymphocyte Count , Cell Adhesion Molecules/analysis , Cell Count , Decidua/chemistry , Decidua/pathology , Dendritic Cells/pathology , Female , Forkhead Transcription Factors/analysis , Humans , Immunohistochemistry , Keratins/analysis , Lectins, C-Type/analysis , Lymphocyte Activation , Lymphocyte Count , Placenta Accreta/pathology , Pregnancy , Receptors, Cell Surface/analysis , T-Lymphocytes, Regulatory/pathology , Trophoblasts/immunology , Trophoblasts/pathology , Trophoblasts/physiology
20.
Int J Clin Exp Pathol ; 6(11): 2615-9, 2013.
Article in English | MEDLINE | ID: mdl-24228129

ABSTRACT

A case of a 27 year old G1P0 female with a dichorionic, diamniotic twin pregnancy presenting with premature rupture of membranes found to have omental caking and diffuse yellow-tan peritoneal nodules, clinically suspicious for carcinomatosis. The case work-up showed this to be an example of florid-diffuse peritoneal deciduosis mimicking carcinomatosis which has since resolved 4 months postpartum.


Subject(s)
Carcinoma/pathology , Cesarean Section , Decidua/pathology , Fetal Membranes, Premature Rupture/surgery , Gravidity , Peritoneal Diseases/pathology , Peritoneal Neoplasms/pathology , Adult , Biomarkers, Tumor/analysis , Biopsy , Carcinoma/chemistry , Decidua/chemistry , Diagnosis, Differential , Female , Humans , Immunohistochemistry , Peritoneal Diseases/metabolism , Peritoneal Neoplasms/chemistry , Predictive Value of Tests , Pregnancy , Pregnancy, Twin
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