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1.
Pharmacol Res ; : 105435, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33485996

RESUMO

Our previous studies found that prenatal dexamethasone exposure could cause abnormal follicular development in fetal rats. This study intends to observe the transgenerational inheritance effects of ovarian estrogen inhibition in offspring exposed to dexamethasone (0.2 mg/kg • d) from gestational day 9 (GD9) to GD20 in Wistar rats, and explore the intrauterine programming mechanisms. Prenatal dexamethasone exposure reduced the expression of ovarian cytochrome P450 aromatase (P450arom), the level of serum estradiol (E2) and the number of primordial follicles, while increased the number of atresia follicles before and after birth in F1 offspring rats. At the same time, the expression of miRNA320a-3p in F1 ovaries was down-regulated, and RUNX2 expression increased significantly. These changes were continued to F2 and F3 generations, accompanied by consistently down-regulated miRNA320a-3p expression in oocyte of F1 and F2 adult offspring. In vitro, fetal rat ovaries and KGN human ovarian granulosa cells were treated with dexamethasone. It showed that dexamethasone decreased miRNA320a-3p and P450arom expression, as well as E2 synthesis, and increased RUNX2 expression. All these effects could be reversed by the GR antagonist RU486. The overexpression of miRNA320a-3p in vitro could also reverse the effects of dexamethasone on RUNX2, P450arom, and E2 levels. The dual-luciferase reporter gene experiment further confirmed the direct targeted regulation of miRNA320a-3p on RUNX2. These results indicate that prenatal dexamethasone exposure induces ovarian E2 synthesis inhibition mediated by the GR/miRNA320a-3p/RUNX2/P450arom cascade signal in fetal rat ovary, which has transgenerational inheritance effects and may related to the inhibited miRNA320a-3p expression in oocyte.

2.
Anal Chem ; 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33296189

RESUMO

Fetal nucleated red blood cells (fNRBCs) in maternal peripheral blood containing the whole genetic information of the fetus may serve for noninvasive pregnant diagnostics (NIPD). However, the fetal cell-based NIPD is seriously limited by the poor purity of the isolated fNRBCs. Recently, the biomimetic cell membrane-camouflaged nanoparticles containing outstanding features have been widely used to detect and isolate rare cells from the peripheral blood samples. In this work, enythrocyte (RBC) and leukocyte (WBC) membranes are fused and coated onto magnet nanoparticles and then modified with anti-CD147 to isolate fNRBCs from the maternal peripheral blood with significant efficiency (∼90%) and purity (∼87%) in simulated spiked blood samples. Further, fNRBCs were isolated and identified from a series of maternal peripheral blood samples coming from pregnant women of 11-13 gestational weeks, and different chromosomal aneuploidies were diagnosed using fNRBCs isolated from maternal blood in early pregnancy. Our strategy may offer additional opportunity to overcome the limitations of current cell-based NIPD platforms.

3.
Reproduction ; 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33258800

RESUMO

Polycystic ovary syndrome (PCOS) is a common endocrine disorder accompanied by chronic low-grade inflammation; its etiology is still undefined. This study investigated the expression of CXCL12, CXCR4, and CXCR7 in PCOS rats and their role in regulation of apoptosis. To accomplish this, we established an in vivo PCOS rat model and studied KGN cells (human ovarian granulosa cell line) in vitro. In PCOS rats, the ovarian expression of CXCL12, CXCR4, and CXCR7 was reduced, and the apoptosis rate of granulosa cells was increased, accompanied by decreased expression of BCL2 and increased expression of BAX and cleaved CASPASE3 (CASP3). We further showed that recombinant human CXCL12 treatment upregulated BCL2, downregulated BAX, and cleaved CASP3 in KGN cells to inhibit their apoptosis in a concentration-dependent manner; moreover, the effect of CXCL12 was weakened by CXCR4 antagonist AMD3100 and anti-CXCR7 neutralizing antibody. In conclusion, PCOS rats showed decreased CXCL12, CXCR4, and CXCR7 expression and increased apoptosis rate of ovarian granulosa cells. Further, in human KGN cells, CXCL12 regulated the expression of BAX, BCL2, and cleaved CASP3 to inhibit apoptosis through CXCR4- and CXCR7-mediated signal transmission. These findings may provide a theoretical and practical basis for illuminating the role of proinflammatory cytokines in the pathogenesis of PCOS.

4.
J Cell Mol Med ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33201593

RESUMO

Studies have reported that non-receptive endometrium or abnormal decidualization was closely related to recurrent implantation failure (RIF). MLL1 is a histone H3 lysine 4 trimethylation (H3K4me3) transferase that regulates the transcriptional activation of target genes. The role of MLL1 has been underexplored during decidualization. In our research, we found the expression of MLL1 was closely related to endometrial receptivity, and it was responsible to hormone stimulation. Inhibiting the function of MLL1 by MM102 reduced the transformation of HESCs. Furthermore, down-regulation of MLL1 by siRNA transfection significantly decreased PGR and its target genes expression. MLL1 act as a co-activator of ERα, and both of them were recruited to PGR regulatory regions, thus promote PGR transcription. Our study showed that MLL1 plays a key role in promoting progesterone signalling transmission.

5.
J Mol Endocrinol ; 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33151904

RESUMO

The aberrant histone methylation patterns contribute to the pathogenesis of endometriosis (EM). Mixed lineage leukemia 1 (MLL1), a histone methyltransferase, is crucial for gene expression by catalyzing the trimethylation of histone 3 lysine 4 (H3K4me3) in gene promoter. This study aimed to explore whether MLL1 is involved in EM-related infertility. The expressions of MLL1 and H3K4me3 were analyzed in the eutopic endometria from EM women with infertility (n=22) and the normal endometria from EM-free women (n=22). Mouse EM model was established. The MLL1 and H3K4me3 expression patterns in mice endometria of early pregnancy were also investigated. Immortalized human endometrial stromal cells (iESCs) were cultured and underwent in vitro decidualization. The chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) was performed to find the target gene of MLL1 during decidual process. Results showed that both MLL1 and H3K4me3 decreased in the eutopic endometrium from EM patients compared to that in the normal endometrium. During early pregnancy and the decidual process, MLL1 and H3K4me3 were significantly upregulated in stromal cells. ChIP-seq and ChIP-qPCR found that the cytochrome c oxidase subunit 4I 2 (COX4I2) was directly targeted by MLL1. The dominance of COX4I2-containing enzyme induced the expression of hypoxia-inducible factor-2α (HIF-2α), whose expression in the peri-implantation endometrium is essential for embryo implantation. Further results showed that MLL1 was directly regulated by progesterone (P4) - P4 receptors (PRs). Our study proved that MLL1 was involved in EM-related infertility, which may provide a novel approach to treat the nonreceptive endometrium in EM patients.

6.
J Assist Reprod Genet ; 37(12): 2929-2945, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33073301

RESUMO

PURPOSE: We performed a systematic review and meta-analysis of available literature to investigate the efficacy of the intracytoplasmic sperm injection (ICSI) in couples with non-male factor with respect to the clinical outcomes. METHODS: The literature search was based on EMBASE, PubMed, and the Cochrane Library. All studies published after 1992 until February 2020 and written in English addressing patients in the presence of normal semen parameters subjected to ICSI and in vitro fertilization (IVF) were eligible. Reference lists of retrieved articles were hand-searched for additional studies. The primary outcomes were fertilization rate, clinical pregnancy rate, and implantation rate; the secondary outcomes were good-quality embryo rate, miscarriage rate, and live birth rate. RESULTS: Four RCTs and twenty-two cohort studies fulfilling the inclusion criteria were included. Collectively, a meta-analysis of the outcomes in RCTs showed that compared to IVF, ICSI has no obvious advantage in fertilization rate (RR = 1.16, 95% CI: 0.83-1.62), clinical pregnancy rate (RR = 1.04, 95% CI: 0.66-1.64), implantation rate (RR = 1.12, 95% CI: 0.67-1.86), and live birth rate (RR = 1.17, 95% CI: 0.43-3.15). Pooled results of cohort studies demonstrated a statistically significant higher fertilization rate (RR = 1.16, 95% CI: 1.03-1.31) and miscarriage rate (RR = 1.04, 95% CI: 1.01-1.06) in the ICSI group; furthermore, higher clinical pregnancy rate (RR = 0.85, 95% CI: 0.77-0.94), implantation rate (RR = 0.78, 95% CI: 0.65-0.95), and live birth rate (RR = 0.86, 95% CI: 0.79-0.94) was founded in the IVF group; no statistically significant difference was observed in good-quality embryo rate (RR = 0.98, 95% CI: 0.93-1.04). CONCLUSION: ICSI has no obvious advantage in patients with normal semen parameters. Enough information is still not available to prove the efficacy of ICSI in couples with non-male factor infertility comparing to IVF.

7.
Biomed Microdevices ; 22(4): 75, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33079273

RESUMO

Being easy, safe and reliable, non-invasive prenatal diagnosis (NIPD) has been greatly pursued in recent years. Holding the complete genetic information of the fetus, fetal nucleated red blood cells (fNRBCs) are viewed as a suitable target for NIPD application. However, effective separating fNRBCs from maternal peripheral blood for clinic use still faces great challenges, given that fNRBCs are extremely rare in maternal blood circulation. Here, by combining the high-throughput inertial microfluidic chip with multifunctional microspheres as size amplification, we develop a novel method to isolate fNRBCs with high performance. To enlarge the size difference between fNRBCs and normal blood cells, we use the gelatin coated microspheres to capture fNRBCs with anti-CD147 as specific recognizer at first. The size difference between fNRBCs captured by the microspheres and normal blood cells makes it easy to purify the captured fNRBCs through the spiral microfluidic chip. Finally, the purified fNRBCs are mildly released from the microspheres by enzymatically degrading the gelatin coating. Cell capture efficiency about 81%, high purity of 83%, as well as cell release viability over 80% were achieved using spiked samples by this approach. Additionally, fNRBCs were successfully detected from peripheral blood of pregnant women with an average of 24 fNRBCs per mL, suggesting the great potential of this method for clinical non-invasive prenatal diagnosis.

8.
Arch Biochem Biophys ; 693: 108571, 2020 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-32898567

RESUMO

Chemotherapy resistance is one of the major challenges for the treatment of hepatocellular carcinoma (HCC). In order to investigate the mechanisms involved in chemoresistance of HCC, we established cisplatin (CDDP) and doxorubicin (Dox) resistant HCC cells. The expression of transcriptional coactivator with PDZ-binding motif (TAZ), one of the major downstream effectors of Hippo pathway, was upregulated in chemoresistant HCC cells. Targeted inhibition of TAZ via its siRNAs can restore CDDP and Dox sensitivity of chemoresistant HCC cells. The upregulation of TAZ increased the expression of IL-8 in HCC/CDDP and HCC/Dox cells. Recombinant IL-8 (rIL-8) antagonized the increased chemosensitivity mediated by TAZ knockdown. Mechanistically, TAZ can directly bind with the promoter of IL-8 to activate its transcription in chemoresistant HCC cells. Collectively, our data showed that TAZ-regulated expression of IL-8 was involved in chemoresistance of HCC cells. It indicated that targeted inhibition of TAZ/IL-8 axis might be helpful to improve chemotherapy efficiency for HCC.

9.
Exp Ther Med ; 20(3): 1879-1888, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32782496

RESUMO

Pre-eclampsia is a complication that occurs during pregnancy, the pathological feature of which is a change in vascular endothelial homeostasis. microRNA (miR)-646 is an anti-angiogenic miRNA that has been indicated to exhibit potential anti-angiogenic effects in endothelial cells cultured in vitro and in ischemia-induced angiogenesis. However, whether miR-646 has therapeutic potential in placental angiogenesis in pre-eclampsia remains to be determined. In the current study, human peripheral blood-derived endothelial progenitor cells (EPCs) were isolated to study the coordination between miR-646, vascular endothelial growth factor (VEGF)-A and hypoxia-inducible factor (HIF)-1α expression in preeclampsia EPCs. EPCs were isolated from human peripheral blood to demonstrate a potential interaction between miR-646 and targets (VEGF-A) in vitro. The number of EPCs and the expression of miR-646 in patients with preeclampsia was detected, and the effects of miR-646 on EPC function and preeclampsia angiogenesis was assessed. Clinical specimens demonstrated that miR-646 expression was enhanced in pregnancy with preeclampsia. The results indicated that miR-646 suppressed EPCs multiplication, differentiation and migration. miR-646 was observed to exert an anti-angiogenic function by suppressing the expression of angiogenic cytokines VEGF-A and HIF-1α. Additionally, luciferase results displayed that miR-646 downregulated VEGF-A expression by directly binding to a specific sequence in its 3'-untranslated region. The results of the current study demonstrated that the miR-646/VEGF-A/HIF-1α axis is significant for angiogenic properties of EPCs in vitro and in vivo placental vasculogenesis. The results of the present study provide a new insight into microRNA regulation of vessel homeostasis and angiogenesis, and a basis for alternative treatments for patients with pre-eclampsia.

10.
Cell Transplant ; 29: 963689720925055, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32693638

RESUMO

This paper aimed to evaluate whether human cytomegalovirus (HCMV) infection in extravillous cytotrophoblasts (EVT) could shift the balance between regulatory T (Treg) and T-helper type 17 (Th17) cells in vitro. In this study, primary EVT isolated from first trimester placental tissues were infected with HCMV, and conditional media were harvested after cultivation for 72 h. T lymphocytes were cultured in the presence or absence of HCMV-infected conditional media. The frequencies of Th17 or Treg cells from HCMV group were significantly lower or higher than those from the control group, with the expression of corresponding key cytokines at both messenger ribonucleic acid and secretion levels, respectively. The ratio of Treg to Th17 cells was significantly lower in HCMV group than that in control group (P < 0.01). In conclusion, tiled Th17/Treg balance at maternal-fetal interface exists after HCMV infection.

11.
J Med Virol ; 2020 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-32621617

RESUMO

In the past several months, the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated infection (coronavirus disease 2019 [COVID-19]) developed rapidly and has turned into a global pandemic. Although SARS-CoV-2 mainly attacks respiratory systems, manifestations of multiple organs have been observed. A great concern was raised about whether COVID-19 may affect male reproductive functions. In this study, we collected semen specimens from 12 male COVID-19 patients for virus detection and semen characteristics analysis. No SARS-CoV-2 was found in semen specimens. Eight out of 12 patients had normal semen quality. We also compared the sex-related hormone levels between 119 reproductive-aged men with SARS-CoV-2 infection and 273 age-matched control men. A higher serum luteinizing hormone (LH) and a lower ratio of testosterone (T) to LH were observed in the COVID-19 group. Multiple regression analysis indicated that serum T: LH ratio was negatively associated with white blood cell counts and C-reactive protein levels in COVID-19 patients. It's the first report about semen assessment and sex-hormone evaluation in reproductive-aged male COVID-19 patients. Although further study is needed to clarify the reasons and underlying mechanisms, our study presents an abnormal sex hormone secretion among COVID-19 patients, suggesting that attention should be paid to reproductive function evaluation in the follow-up.

12.
Toxicol Lett ; 332: 97-106, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-32599024

RESUMO

As important members in steroids related signal pathways, bile acids are very important in regulating substance metabolism and immune homeostasis. However, bile acids are highly cytotoxic, and the excessive accumulation can induce several abnormalities such as cholestatic liver injury. It is known that the bile acid metabolism alters during pregnancy and mostly will not result in pathologies. However, the effect of dexamethasone exposure during pregnancy on bile acid metabolism is still unknown. In this study, pregnant Wistar rats were subcutaneously administered dexamethasone (0.2 mg/kg.d) or saline from gestation day 9-21, while virgin rats were given the same treatment for 13 days. We found that, physiological pregnancy or dexamethasone exposure during non-pregnancy did not affect maternal serum TBA level and liver function. Nevertheless, dexamethasone exposure during pregnancy increased serum TBA level and accompanied with liver injury. Furthermore, we discovered that the conservation of bile acid homeostasis under pregnancy or dexamethasone exposure was maintained through compensatory pathways. However, dexamethasone exposure during pregnancy tipped the balance of liver bile acid homeostasis by increasing classical synthesis and decreasing efflux and uptake. In addition, dexamethasone exposure during pregnancy also increased serum estrogen level and nuclear receptors mRNA expression levels. Finally, two-way ANOVA analysis showed that dexamethasone exposure during pregnancy could induce or facilitate maternal cholestasis and liver injury by up-regulating ERα and CYP7A1 expression. This study confirmed that dexamethasone exposure during pregnancy was related to maternal intrahepatic cholestasis of pregnancy and should be carefully monitored in clinical settings.


Assuntos
Ácidos e Sais Biliares/metabolismo , Dexametasona/toxicidade , Animais , Colestase Intra-Hepática , Colesterol 7-alfa-Hidroxilase/biossíntese , Estrogênios/sangue , Feminino , Hormônios Esteroides Gonadais/sangue , Homeostase/efeitos dos fármacos , Infusões Subcutâneas , Testes de Função Hepática , Gravidez , Ratos , Ratos Wistar , Receptores Estrogênicos/biossíntese
13.
Mol Genet Genomic Med ; 8(8): e1279, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32463164

RESUMO

BACKGROUND: Placental mosaicism is one of the major reasons for noninvasive prenatal testing (NIPT) discrepancy. Herein, we discovered a rare case of placenta with complex karyotypes that caused false-positive and false-negative results in noninvasive prenatal testing. METHODS: Next-generation sequencing (NGS) and Quantitative fluorescent polymerase chain reaction (QF-PCR) were performed on the cord blood sample, fetal tissues, and eight placental biopsies. Fluorescent In Situ Hybridization (FISH) and karyotyping were also carried to confirm the fetal genome status. RESULTS: The results suggested that the fetal chromosome was 47,XXX and the placenta had three karyotypes of 48,XXX,+21, 47,XX,+21, and 47,XXX. QF-PCR indicated that the extra chromosome 21 and chromosome X were all from the father. It is speculated that the zygote may have 48,XXX,+21 karyotype and trisomy rescue could be the main mechanism for the development of the homogeneous fetus and complex mosaic placenta. CONCLUSION: Overall, the complicated nature of our case underlines the importance of discussing with parents the possibility of both atypical and discordant results during preconfirmatory amniocentesis counseling and consent.

14.
J Allergy Clin Immunol ; 146(1): 101-109.e1, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32437740

RESUMO

BACKGROUND: Immunologic dysfunction due to coronavirus disease 2019 (COVID-19) is closely related to clinical prognosis, and the inflammatory response of pregnant women may affect the directional differentiation and function of fetal immune cells. OBJECTIVE: We sought to analyze the immune status of newborns from mothers with COVID-19 in the third trimester. METHODS: Along with collecting the clinical data from 51 newborns and their respective mothers, we recorded the immunophenotypes and cytokine and immunoglobulin levels of the newborns. RESULTS: None of the 51 newborns showed fever or respiratory distress during hospitalization. Detection of severe acute respiratory syndrome coronavirus 2 nucleic acid in pharyngeal swabs was negative. Except for the low level of CD16-CD56 cells, the count and proportion of lymphocytes, CD3, CD4, CD8, and CD19 were all in the normal range. Moreover, the serum IgG and IgM levels were within the normal range, whereas IL-6 showed increased levels. There was no correlation between maternal COVID-19 duration and the lymphocyte subsets or cytokine levels (IFN-γ, IL-2, IL-4, IL-6, IL-10, and TNF-α). There was a positive correlation between IL-6 and IL-10 levels and CD16-CD56 cells. One (1.96%) infant with an extremely elevated IL-6 concentration developed necrotizing enterocolitis in the third week after birth, and the remaining 50 infants did not show abnormal symptoms through the end of the follow-up period. CONCLUSIONS: COVID-19 in the third trimester did not significantly affect the cellular and humoral immunity of the fetus, and there was no evidence that the differentiation of lymphocyte subsets was seriously unbalanced.


Assuntos
Infecções por Coronavirus/imunologia , Recém-Nascido/imunologia , Pneumonia Viral/imunologia , Complicações Infecciosas na Gravidez/imunologia , Efeitos Tardios da Exposição Pré-Natal/imunologia , Betacoronavirus , China , Feminino , Humanos , Subpopulações de Linfócitos/imunologia , Masculino , Pandemias , Gravidez , Terceiro Trimestre da Gravidez
15.
Am J Obstet Gynecol ; 223(1): 111.e1-111.e14, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32335053

RESUMO

BACKGROUND: The coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2, is a global public health emergency. Data on the effect of coronavirus disease 2019 in pregnancy are limited to small case series. OBJECTIVE: To evaluate the clinical characteristics and outcomes in pregnancy and the vertical transmission potential of severe acute respiratory syndrome coronavirus 2 infection. STUDY DESIGN: Clinical records were retrospectively reviewed for 116 pregnant women with coronavirus disease 2019 pneumonia from 25 hospitals in China between January 20, 2020, and March 24, 2020. Evidence of vertical transmission was assessed by testing for severe acute respiratory syndrome coronavirus 2 in amniotic fluid, cord blood, and neonatal pharyngeal swab samples. RESULTS: The median gestational age on admission was 38+0 (interquartile range, 36+0-39+1) weeks. The most common symptoms were fever (50.9%, 59/116) and cough (28.4%, 33/116); 23.3% (27/116) patients presented without symptoms. Abnormal radiologic findings were found in 96.3% (104/108) of cases. Of the 116 cases, there were 8 cases (6.9%) of severe pneumonia but no maternal deaths. One of 8 patients who presented in the first trimester and early second trimester had a missed spontaneous abortion. Of 99 patients, 21 (21.2%) who delivered had preterm birth, including 6 with preterm premature rupture of membranes. The rate of spontaneous preterm birth before 37 weeks' gestation was 6.1% (6/99). One case of severe neonatal asphyxia resulted in neonatal death. Furthermore, 86 of the 100 neonates tested for severe acute respiratory syndrome coronavirus 2 had negative results; of these, paired amniotic fluid and cord blood samples from 10 neonates used to test for severe acute respiratory syndrome coronavirus 2 had negative results. CONCLUSION: Severe acute respiratory syndrome coronavirus 2 infection during pregnancy is not associated with an increased risk of spontaneous abortion and spontaneous preterm birth. There is no evidence of vertical transmission of severe acute respiratory syndrome coronavirus 2 infection when the infection manifests during the third trimester of pregnancy.


Assuntos
Infecções por Coronavirus/patologia , Pneumonia Viral/patologia , Complicações Infecciosas na Gravidez/virologia , Aborto Espontâneo/virologia , Adulto , Líquido Amniótico/virologia , Betacoronavirus , China , Infecções por Coronavirus/complicações , Feminino , Sangue Fetal/virologia , Humanos , Recém-Nascido , Transmissão Vertical de Doença Infecciosa , Pandemias , Pneumonia Viral/complicações , Gravidez , Complicações Infecciosas na Gravidez/patologia , Resultado da Gravidez , Nascimento Prematuro/virologia
16.
Ann Transl Med ; 8(5): 233, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32309380

RESUMO

Background: Clinical studies have showed that dexamethasone exposure during pregnancy could cause fetal growth retardation, but the mechanism by which prenatal dexamethasone exposure influences placental nutrient transport is still unclear. This study investigated the impacts of prenatal dexamethasone on the placental oxygen and nutrient transport. Methods: Pregnant Wistar rats were subcutaneously administered with dexamethasone from day 9 to day 20 of gestation at 0.2 or 0.8 mg/kg·d. Pregnant rats were sacrificed on gestational day 20. The placental tissue was collected for analysis. Results: Prenatal dexamethasone exposure (PDE) declined the fetal weight and increased the intrauterine growth retardation (IUGR) rate in a dose-dependent manner. The total placental volume and the length, density and surface area of fetal capillaries in the labyrinth zone reduced in a dose-dependent manner. In addition, the thickness of syncytial membrane dose-dependently increased, resulting in a dose-dependent decrease in oxygen diffusion capacity. Furthermore, after PDE, the nutrient transport area and oxygen diffusion capacity of male placenta were lower than that of female placenta. The mRNA and protein expression of placental nutrient transporters including glucose transporter 1 (GLUT1), glucose transporter 3 (GLUT3), L-type amino acid transporter 1 (LAT1), lipoprotein lipase (LPL) and scavenger receptor class B type 1 (SRB1) increased in female placenta. However, in male placenta, the expression of LAT1, LPL and SRB1 was significantly decreased and GLUT1 and GLUT3 have a decrease trend. We further investigated the expression of insulin-like growth factor 1 (IGF1) and insulin-like growth factor 2 (IGF2) related to placental and fetal growth and development. Our study showed that the expression of IGF1 was significantly decreased both in male and female placentas after PDE. But the expression of IGF2 was significantly increased in female placentas while significantly decreased in male placentas. Conclusions: Our study shows prenatal dexamethasone exposure exerts sex-specific influence on the placental oxygen and nutrient transport. This might be ascribed to the differential expression of IGF2 after PDE. These findings provide evidence on the dexamethasone-induced toxicity to the placenta and fetal development.

17.
Mucosal Immunol ; 13(5): 743-752, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32203061

RESUMO

Ectopic pregnancy is the major cause of maternal morbidity and mortality in the first trimester of pregnancy. Tubal ectopic pregnancy (TEP) accounts for nearly 98% of all ectopic pregnancies. TEP is usually associated with salpingitis but the underlying mechanism in salpingitis leading to TEP remains unclear. Adrenomedullin (ADM) is a peptide hormone abundantly expressed in the fallopian tube with potent anti-inflammatory activities. Its expression peaks at the early luteal phase when the developing embryo is being transported through the fallopian tube. In the present study, we demonstrated reduced expression of ADM in fallopian tubes of patients with salpingitis and TEP. Using macrophages isolated from the fallopian tubes of these women, our data revealed that the salpingistis-associated ADM reduction contributed to aggravated pro-inflammatory responses of the tubal macrophages resulting in production of pro-inflammatory and pro-implantation cytokines IL-6 and IL-8. These cytokines activated the expression of implantation-associated molecules and Wnt signaling pathway predisposing the tubal epithelium to an adhesive and receptive state for embryo implantation. In conclusion, this study provided evidence for the role of ADM in the pathogenesis of TEP through regulating the functions of tubal macrophages.

18.
Lancet ; 395(10226): 809-815, 2020 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-32151335

RESUMO

BACKGROUND: Previous studies on the pneumonia outbreak caused by the 2019 novel coronavirus disease (COVID-19) were based on information from the general population. Limited data are available for pregnant women with COVID-19 pneumonia. This study aimed to evaluate the clinical characteristics of COVID-19 in pregnancy and the intrauterine vertical transmission potential of COVID-19 infection. METHODS: Clinical records, laboratory results, and chest CT scans were retrospectively reviewed for nine pregnant women with laboratory-confirmed COVID-19 pneumonia (ie, with maternal throat swab samples that were positive for severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) who were admitted to Zhongnan Hospital of Wuhan University, Wuhan, China, from Jan 20 to Jan 31, 2020. Evidence of intrauterine vertical transmission was assessed by testing for the presence of SARS-CoV-2 in amniotic fluid, cord blood, and neonatal throat swab samples. Breastmilk samples were also collected and tested from patients after the first lactation. FINDINGS: All nine patients had a caesarean section in their third trimester. Seven patients presented with a fever. Other symptoms, including cough (in four of nine patients), myalgia (in three), sore throat (in two), and malaise (in two), were also observed. Fetal distress was monitored in two cases. Five of nine patients had lymphopenia (<1·0 × 109 cells per L). Three patients had increased aminotransferase concentrations. None of the patients developed severe COVID-19 pneumonia or died, as of Feb 4, 2020. Nine livebirths were recorded. No neonatal asphyxia was observed in newborn babies. All nine livebirths had a 1-min Apgar score of 8-9 and a 5-min Apgar score of 9-10. Amniotic fluid, cord blood, neonatal throat swab, and breastmilk samples from six patients were tested for SARS-CoV-2, and all samples tested negative for the virus. INTERPRETATION: The clinical characteristics of COVID-19 pneumonia in pregnant women were similar to those reported for non-pregnant adult patients who developed COVID-19 pneumonia. Findings from this small group of cases suggest that there is currently no evidence for intrauterine infection caused by vertical transmission in women who develop COVID-19 pneumonia in late pregnancy. FUNDING: Hubei Science and Technology Plan, Wuhan University Medical Development Plan.


Assuntos
Betacoronavirus , Infecções por Coronavirus/transmissão , Transmissão Vertical de Doença Infecciosa , Pneumonia Viral/transmissão , Complicações Infecciosas na Gravidez , Betacoronavirus/isolamento & purificação , Betacoronavirus/patogenicidade , Cesárea , Infecções por Coronavirus/complicações , Tosse/etiologia , Dispepsia/etiologia , Feminino , Febre/etiologia , Humanos , Recém-Nascido , Mialgia/etiologia , Faringite/etiologia , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Resultado da Gravidez , Terceiro Trimestre da Gravidez , Estudos Retrospectivos
19.
Int J Gynaecol Obstet ; 149(2): 130-136, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32196655

RESUMO

OBJECTIVE: To provide clinical management guidelines for novel coronavirus (COVID-19) in pregnancy. METHODS: On February 5, 2020, a multidisciplinary teleconference comprising Chinese physicians and researchers was held and medical management strategies of COVID-19 infection in pregnancy were discussed. RESULTS: Ten key recommendations were provided for the management of COVID-19 infections in pregnancy. CONCLUSION: Currently, there is no clear evidence regarding optimal delivery timing, the safety of vaginal delivery, or whether cesarean delivery prevents vertical transmission at the time of delivery; therefore, route of delivery and delivery timing should be individualized based on obstetrical indications and maternal-fetal status.


Assuntos
Infecções por Coronavirus/terapia , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Pneumonia Viral/terapia , Complicações Infecciosas na Gravidez/terapia , Betacoronavirus , China , Consenso , Infecções por Coronavirus/virologia , Parto Obstétrico/métodos , Feminino , Humanos , Recém-Nascido , Controle de Infecções/métodos , Pandemias , Pneumonia Viral/virologia , Gravidez , Complicações Infecciosas na Gravidez/virologia , Fatores de Risco
20.
Reprod Sci ; 27(4): 963-976, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32124397

RESUMO

The clinical significance of periconceptional folic acid supplementation (FAS) in the prevention of neonatal neural tube defects (NTDs) has been recognized for decades. Epidemiological data and experimental findings have consistently been indicating an association between folate deficiency in the first trimester of pregnancy and poor fetal development as well as offspring health (i.e., NTDs, isolated orofacial clefts, neurodevelopmental disorders). Moreover, compelling evidence has suggested adverse effects of folate overload during perinatal period on offspring health (i.e., immune diseases, autism, lipid disorders). In addition to several single-nucleotide polymorphisms (SNPs) in genes related to folate one-carbon metabolism (FOCM), folate concentrations in maternal serum/plasma/red blood cells must be considered when counseling FAS. Epigenetic information encoded by 5-methylcytosines (5mC) plays a critical role in fetal development and offspring health. S-adenosylmethionine (SAM), a methyl donor for 5mC, could be derived from FOCM. As such, folic acid plays a double-edged sword role in offspring health via mediating DNA methylation. However, the underlying epigenetic mechanism is still largely unclear. In this review, we summarized the link across DNA methylation, maternal FAS, and offspring health to provide more evidence for clinical guidance in terms of precise FAS dosage and time point. Future studies are, therefore, required to set up the reference intervals of folate concentrations at different trimesters of pregnancy for different populations and to clarify the epigenetic mechanism for specific offspring diseases.

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