In order to investigate the beneficial effects of 0.5 or 1.0 g/kg Korean garlic juice against the embryotoxicity of 20 mg/kg methylmercury chloride (MMC, CH3HgCl), pregnant Fisher 344 rats were simultaneously orally administered on day 7 of gestation. On day 20 of gestation the dams were laparotomized under ether anesthesia, and the fetuses were removed and examined for toxicity of methylmercury. Garlic juice depressed the toxicity in terms of some parameters. In the case of simultaneous treatment with 0.1 g/kg garlic juice and MMC, rates of increase were 17.5% in maternal body weight, 13.2% and 41.9% in fetal and litters' weight respectively, and 37.0% in fetal survival rate. Decreasing rates were 10.0% in maternal death rate, and 6.9% and 31.3% in pre- and post-implantation loss respectively. Decreasing rates of mercury levels in dams were 67.2% in liver, 57.6% in brain, 47.2% in kidney, 42.1% in spleen and 40.9% in blood. As well, decreasing rates of mercury level in fetuses were 54.9% in all body burden, 55.9% in liver, 46.7% in kidney and 37% in brain, respectively. The number of fetal ossification centers were reduced by 23.8% to 58.0% following simultaneous treatment with 1.0 g/kg garlic juice. These findings indicated that garlic juice effectively inhibited the embryotoxicity of methylmercury in pregnant Fischer 344 rats.
Animal ; Body Weight/drug effects ; Embryo/drug effects* ; Embryo Loss/prevention & control ; Embryo Loss/chemically induced ; Female ; Fetal Weight/drug effects ; Garlic* ; Methylmercury Compounds/toxicity* ; Methylmercury Compounds/pharmacokinetics ; Osteogenesis/drug effects ; Pregnancy ; Rats ; Rats, Inbred F344 ; Tissue Distribution

Animals ; Blastocyst ; Embryo Loss ; HeLa Cells ; Humans ; Mice ; Nuclear Proteins ; deficiency ; genetics ; metabolism

OBJECTIVESTo investigate the clinical effect of sequential therapeutic intervention Yupei Qisun [compensating for weakness by invigorating Kidney (Shen) and Spleen (Pi) in advance] in Chinese medicine (CM) and hysteroscopic endometrial mechanical stimulation on the treatment of infertile patients with repeated implantation failure (RIF); and to study the differences in patients' endometrial thickness and type on the day of embryo transfer, serum hormone levels on embryo transfer day and clinical pregnancy outcomes.

METHODSIn the clinical study, 168 frozen-thawed embryo transfer (FET) cycles for couples with RIF conforming to the research protocol were randomly divided into three groups: a CM group with 56 cycles (CM combined with FET), a hysteroscopy group with 55 cycles (hysteroscopic endometrial mechanical stimulation), and a control group with 57 cycles (conventional FET). Differences in endometrial thickness on the embryo transfer day, levels of serum estradiol (E2) and progesterone (P) on the embryo transfer day, the E2/P ratio on the embryo transfer day, biochemical and clinical pregnancy rates, implantation rate, abnormal pregnancy rate and other indices were compared among the three groups.

RESULTSEndometrial thickness, E2 and P levels, and the E2/P ratio on embryo transfer day and other factors had no significant differences among groups. The biochemical pregnancy, clinical pregnancy, and implantation rates of the CM and hysteroscopy groups were significantly higher than the control group (P<0.05), and there were no significant differences between these two groups. The abnormal pregnancy rate had no significant difference among the three groups.

CONCLUSIONSSequential therapy of Yupei Qisun could significantly improve the clinical outcomes of rif-fet cycles, being equivalent to hysteroscopic endometrial mechanical stimulation, and provided a reliable method to treat such infertile couples.

Abortion, Habitual ; therapy ; Adult ; Embryo Implantation ; Embryo Loss ; therapy ; Embryo Transfer ; Endometrium ; pathology ; physiopathology ; Female ; Humans ; Hysteroscopy ; Infertility, Female ; pathology ; therapy ; Medicine, Chinese Traditional ; methods ; Physical Stimulation ; methods ; Pregnancy ; Retreatment ; statistics & numerical data

BACKGROUNDChemokines and their receptors have been a research focus in transplantation immunology. Chemokines and their receptors play a role in lymphocyte recruitment and differentiation process. This study aimed to observe whether IL-4 and IL-10 may regulate the expression of chemokine receptors CCR3, CCR5 and CXCR3 on CD4(+) T cells in CBA/JxDBA/2 mouse model and to explore the role of CCR3, CCR5, CXCR3 in immune tolerance in pregnancy.

METHODSThe mouse model of spontaneous abortion (CBA/JxDBA/2) and the normal pregnant mouse model (CBA/JxBALB/c) were used. CBA/JxDBA/2 mice were injected with IL-4 (CBA/JxDBA/2-IL-4), IL-4 and IL-10 (CBA/JxDBA/2-IL-4+IL-10), or normal saline (CBA/JxDBA/2-NS) as a control. The expression of CCR3, CCR5 and CXCR3 on CD4(+) T cells from mouse peripheral blood was measured by the double-labelled FCM method, and the embryo resorption rate was also examined.

RESULTSThe embryo resorption rate in the CBA/JxDBA/2 group without any treatment was significantly higher than that in the CBA/JxBALB/c group (17.9% vs 3.7%, P < 0.01). The embryo resorption rate in the CBA/JxDBA/2 group immunized with IL-4 or IL-4 together with IL-10 was significantly decreased, compared with that in the control and NS groups respectively. CCR3 expression on CD4(+) T cells in the CBA/JxDBA/2 group without any treatment was significantly lower than that in the CBA/JxBALB/c group (0.3738 +/- 0.3575 vs 1.2190 +/- 0.2772, P < 0.01); both CCR5 (3.0900 +/- 1.5603 vs 1.2390 +/- 0.6361, P < 0.01) and CXCR3 (2.4715 +/- 0.9074 vs 0.9200 +/- 0.5585, P < 0.01) expressions on CD4(+) T cells of the CBA/JxDBA/2 group without any treatment were significantly higher than those of the CBA/JxBALB/c group. Significant up-regulation of CCR3 and down-regulation of CXCR3 were found in the CBA/JxDBA/2 group treated with IL-4 (CCR3: 2.0360 +/- 0.6944, CXCR3: 1.3510 +/- 0.5263, P < 0.01) or IL-4 and IL-10 (CCR3: 1.8160 +/- 1.0947, CXCR3:1.0940 +/- 0.7168, P < 0.01). Because of the CCR5, IL-4 and IL-10 (1.9400 +/- 0.8504 vs 3.0900 +/- 1.5603, P < 0.05), but IL-4 alone (2.5310 +/- 1.3595 vs 3.0900 +/- 1.5603, P > 0.05) treatment significantly decreased the expression of CCR5 in CBA/JxDBA/2.

CONCLUSIONSThe abnormal expression of CCR3, CCR5 and CXCR3 on CD4(+) T cells may play an important role in the pathogenesis of spontaneous abortion. The pregnancy immune tolerance may be induced through selective induction of CCR3, CCR5 and CXCR3 expressions by IL-4 together with IL-10.

Animals ; CD4-Positive T-Lymphocytes ; drug effects ; metabolism ; Cells, Cultured ; Embryo Loss ; metabolism ; Embryo, Mammalian ; Female ; Interleukin-10 ; pharmacology ; Interleukin-4 ; pharmacology ; Mice ; Mice, Inbred BALB C ; Pregnancy ; Receptors, CCR3 ; metabolism ; Receptors, CCR5 ; metabolism ; Receptors, CXCR3 ; metabolism

The null mutation of cardiac Na+-Ca2+ exchanger (NCX1) gene in mice caused death of embryo in utero at embryonic day (ED) 9.0-9.5 and this embryonic lethality appears resulted from abnormal heart development. In the present study, we investigated whether transgenic re-expression of NCX1 in mutant cardiac myocytes could rescue these lethal defects. Transgenic mice expressing the canine NCX1 in a cardiac specific manner were bred into the NCX1 knock-out background but did not prevent the fetal lethality associated with the NCX1 null allele. However, the NCX1 knock-out embryos with an NCX1 transgene survived with heart beatings until ED 10.5 which was one day longer than the survival of the NCX1 knock-out embryos (ED 9.5). At ED 10.5, however, the partially rescued NCX1 embryos might have succumbed to the lack of an organized vasculature in the yolk sacs. The placental labyrinth layer was reduced in size and largely avascular. The transgenic re-expression of NCX1 rescued heart beatings and survived longer, but was still insufficient for the mice to be completely rescued. Importantly, NCX1 was observed to express in the yolk sac and the placenta of wild type mice. The results suggest that defects in extra-embryonic compartments are causal to the lethality, and that NCX1 may play an important role in establishing vascularization in extra-embryonic tissues.
Animals ; Embryo/*metabolism/pathology ; Embryo Loss ; Female ; Gene Deletion ; *Gene Expression ; Genetic Complementation Test ; Mice ; Mice, Knockout ; Mice, Transgenic ; Myocytes, Cardiac/metabolism ; Phenotype ; Placenta/metabolism/pathology ; Sodium-Calcium Exchanger/*genetics/*metabolism ; Survival Rate ; Yolk Sac/embryology/metabolism/pathology

Animals ; Cell Nucleus Size ; genetics ; Cell Proliferation ; genetics ; Embryo Loss ; genetics ; pathology ; Embryo, Mammalian ; metabolism ; pathology ; Embryonic Stem Cells ; cytology ; Endoplasmic Reticulum ; genetics ; Homologous Recombination ; Mice ; rab GTP-Binding Proteins ; deficiency ; genetics ; metabolism

OBJECTIVETo investigate chromosomal euploidies in early-stage arrested human embryos.

METHODSTo determine the euploidy status of the 24 chromosomes, 13 embryos were analyzed, which included 5 arrested at 4-cell stage, 4 arrested at 8-cell stage, and 4 embryos at blastocyst stage regardless of their morphological scores. All embryos were subjected to biopsy, whole genome amplification, and array comparative genome hybridization analysis.

RESULTSChromosome euploidies of the arrested embryos can be normal, aberrant and chaotic. Mosaicism is prevalent in early stage cleavage, whilst most of the blastocysts, even with poor morphology, are normal diploid.

CONCLUSIONArrested embryo may have normal chromosomes euploidy. Mosaicism is common in cleavage stage embryos. Early stage embryo arrest may not be solely attributable to chromosomal aneuploidies and needs further research.

Adult ; Blastocyst ; cytology ; Cell Cycle Checkpoints ; Chromosome Aberrations ; Comparative Genomic Hybridization ; Embryo Loss ; genetics ; Female ; Fertilization in Vitro ; Humans ; Infertility ; genetics ; therapy ; Male ; Middle Aged ; Pregnancy

BACKGROUNDPrevious studies have shown that local immune cells in the feto-maternal interface are recruited from peripheral blood, and that chemokines and their receptors play an initial and key role in this recruitment process. In this study, we aimed to determine whether spontaneous abortion is associated with the expression of chemokine receptors CCR3, CCR5, and CXCR3 on CD4(+) T cells.

METHODSPeripheral blood, spleen, and thymus were collected from the spontaneous abortion mouse model CBA/JxDBA/2 (SA group, n = 14), the normal pregnant mouse model CBA/JxBALB/c (NP group, n = 13), and normal non-pregnant CBA/J mice (NNP group, n = 11). The number of chemokine receptors CCR3, CCR5, and CXCR3 expressed on CD4(+) T cells was measured by double-label flow cytometry (FCM) method.

RESULTSIn peripheral blood, the SA group had significantly lower CCR3 expression (P < 0.01) and higher CCR5 and CXCR3 expression (P < 0.01) on CD4(+) T cells than did the NP group. But comparing these chemokines between the SA and NNP groups, there was no significant difference (P > 0.05). In spleen, the SA group expressed significantly lower CCR3 expression (P < 0.01) and higher CCR5 and CXCR3 expression (P < 0.05) on CD4(+) T cells than did the NP group. When compared with the NNP group, the SA group had significantly higher CCR3 expression (P < 0.01), but was not statistically different with regards to the other two chemokines (P > 0.05). In thymus, the SA group had significantly lower CCR3 expression (P < 0.05) and higher CXCR3 expression (P < 0.05) on CD4(+) T cells than the NP group, with no significant difference in CCR5 expression (P > 0.05). Compared with the NNP group, the SA group had higher CCR3 expression (P < 0.01), but there was no statistical difference in CXCR3 and CCR5 expression (P > 0.05) between the two groups.

CONCLUSIONThe abnormal expression of CCR3, CCR5 and CXCR3 on CD4(+) T cells may play an important role in the pathogenesis of spontaneous abortion.

Animals ; CD4-Positive T-Lymphocytes ; metabolism ; Embryo Loss ; Female ; Flow Cytometry ; Gene Expression Regulation ; Male ; Mice ; Mice, Inbred BALB C ; Pregnancy ; Receptors, CCR3 ; metabolism ; Receptors, CCR5 ; metabolism ; Receptors, CXCR3 ; metabolism ; Spleen ; metabolism ; Thymus Gland ; metabolism

BACKGROUNDInhibition of the key costimulatory signals results in T cell anergy, indicating the alloantigen-specific immunologic unresponsiveness. In this study, the effect of blockage of costimulatory signal CD(86) on murine abortion-prone model was studied.

METHODSThirty CBA/J female mice cohabitated with DBA/2 male or BALB/c male mice were investigated. CBA/J x DBA/2 matings were used as the abortion-prone model, and CBA/J x BALB/c matings were used as the normal pregnant model. The abortion-prone models were divided into experimental and control groups, and the normal pregnant models were set as a normal group (10 mice in each group). The mice in the experimental group were treated with anti-mouse CD(86) monoclonal antibody (mAb) (100 microg) on day 4.5 of gestation, while the controls received irrelevant-isotype matched rat IgG(2b). As for the normal group, nothing was given to the mice. The mice were killed on day 13.5 of gestation, embryo resorption rate and the expression of transforming growth factor beta(1) (TGF-beta(1)), plasminogen activator inhibitor 1 (PAI-1), and matrix metalloproteinase 9 (MMP-9) were detected. Then the data were analyzed by Chi-square test and Fisher's exact test.

RESULTSThe embryo resorption rate in the experimental (8.2%) and normal groups (7.7%) was significantly lower than that of the control (23.5%, P < 0.05). No significant difference was detected between the experimental and normal groups (P > 0.05). The positive expression rates of TGF-beta(1) and PAI-1 proteins in the experimental and normal groups were significantly higher than those in the control group (P < 0.05). The positive expression rate of MMP-9 protein in the experimental and normal groups was significantly lower than that in the control group (P < 0.05). No significant difference in the positive expression rates of the three proteins was detected between the experimental and normal groups (P > 0.05).

CONCLUSIONSBlockage of costimulatory signal CD(86) at early pregnancy can treat uncertain recurrent spontaneous abortion by stimulating the expression of TGF-beta(1), MMP-9 and PAI-1 and reducing the embryo resorption rate.

Abortion, Habitual ; therapy ; Animals ; Antibodies, Monoclonal ; therapeutic use ; B7-2 Antigen ; immunology ; physiology ; Embryo Loss ; prevention & control ; Female ; Immunohistochemistry ; Male ; Matrix Metalloproteinase 9 ; analysis ; Mice ; Mice, Inbred Strains ; Plasminogen Activator Inhibitor 1 ; analysis ; Pregnancy ; Signal Transduction ; Transforming Growth Factor beta1 ; analysis

OBJECTIVETo evaluate its mechanism of inducing the maternal-fetal immune tolerance by studying the effects of Shoutai pills on the expression of Th1/Th2 cytokine and pregnancy in maternal-fetal interface of mice with recurrent spontaneous abortion (RSA).

METHODThe normal pregnancy and RSA model were respectively induced with CBA/J x BALB/c and CBA/J x DBA/2. The mice with RSA were randomly divided into model group and low, middle and high dose groups of Shoutai pills. The mice were killed in 14 days after administration and embryo resorption rate was counted and their decidual and placental tissues were co-cultured to detect the expressions of IL-4, IL-10, IFN-gamma and TNF-alpha with ELISA.

RESULTThe embryo resorption rate of the model group was significantly higher than the normal pregnancy, middle and high dose groups of Shoutai pills could decreased the embryo resorption rate of the mice with RSA (P < 0.05). All the doses in 3 groups of Shoutai pills could decreased the expression of IFN-gamma and TNF-alpha (P < 0. 05) and there was no obvious difference between normal pregnancy group and all groups of Shoutai pills. Middle and high doses of Shoutai pills could increased the expression of IL-4 and IL-10 (P < 0.05) and there was no obvious differences between normal pregnancy and high dose group of Shoutai pills.

CONCLUSIONThe mechanism about Shoutai pills can change Th1 /Th2 cytokine towards Th2 bias, which induced the maternal-fetal immune tolerance.

Abortion, Habitual ; drug therapy ; immunology ; pathology ; Animals ; Cytokines ; immunology ; Drugs, Chinese Herbal ; administration & dosage ; Embryo Loss ; Female ; Humans ; Male ; Maternal-Fetal Exchange ; drug effects ; Mice ; Mice, Inbred BALB C ; Mice, Inbred CBA ; Mice, Inbred DBA ; Pregnancy ; Pregnancy Outcome ; Th1 Cells ; drug effects ; immunology ; Th2 Cells ; drug effects ; immunology