OBJECTIVE: To investigate the efficacy of Bushen Huoxue Fang (BSHXF, a traditional Chinese medicine formula) for improving recurrent spontaneous abortion (RSA) in mice and the role of tyrosine kinase (JAK2) and transcriptional activator (STAT3) signaling pathway in its therapeutic mechanism. METHODS: Female CBA/J mice were caged with male DBA/2 mice to establish RSA mouse models, which were randomly divided into model group, dydrogesterone group and BSHXF group, with the female mice caged with male BALB/c mice as the control group (n=6). From the first day of pregnancy, the mice were subjected to daily intragastric administration of BSHXF, dydrogesterone, or distilled water (in control and model groups) for 12 days. After the treatments, serum levels of antithrombin III (AT-III), activated protein C (APC), tissue plasminogen activator (t-PA), progesterone, human chorionic gonadotropin (HCG), and estradiol (E2) were detected in each group using ELISA. HE staining was used to observe the morphological changes of the endometrium of the mice. Western blotting was performed to determine the expressions of p-JAK2, p-Stat3 and Bcl-2 in the placenta of the mice. RESULTS: Compared with the control mice, the mouse models of RSA showed a significantly increased embryo loss rate with decreased serum levels of AT-III, T-PA, progesterone, APC and HCG, increased placental expressions of p-JAK2, p-STAT3 and Bax, and decreased expression of Bcl-2 (P < 0.05). Treatments with BSHXF and dydrogesterone both increased serum levels of AT-III, t-PA and HCG in the mouse models; Serum APC level was significantly reduced in BSHXF group and serum progesterone level was significantly increased in dydrogesterone group (P < 0.05). CONCLUSION BSHXF can improve the prethrombotic state and inhibit cell apoptosis by downregulating the JAK2/STAT3 pathway to increase the pregnancy rate in mouse models of RSA.
Animals ; Mice ; Abortion, Habitual/prevention & control* ; Signal Transduction ; Down-Regulation ; Disease Models, Animal

OBJECTIVETo find a method without corticosteroids, aspirin or heparin for treatment of anticardiolipin antibody-positive early recurrent spontaneous abortion (AARSA).

METHODSTwenty-three patients of AARSA in the treated group were treated with Chinese herbal medicine (CHM) plus human chorionic gonadotropin and progesterone, and 18 patiens in the control group were treated with multi-vitamin only. The change of anticardiolipin antibody was determined by enzyme linked immunoabsorbent assay (ELISA).

RESULTSAfter treatment, anticardiolipin antibody negative converted in 20 cases (86.9%) of the treated group. The cure rate of abortion in the treated group was 82.6% (19/23), which was raised to 95% (19/20) in those patients with antibody negative conversion, while in the control group, it was 16.7% (3/18) merely, comparison between the two groups in cure rate showed significant difference (P < 0.01).

CONCLUSIONCHM plus human chorionic gonadotropin and progesterone could cure AARSA effectively.

Abortion, Habitual ; immunology ; prevention & control ; Abortion, Spontaneous ; immunology ; prevention & control ; Adult ; Antibodies, Anticardiolipin ; blood ; Chorionic Gonadotropin ; therapeutic use ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Phytotherapy ; Pregnancy ; Pregnancy Trimester, First ; Progesterone ; therapeutic use

OBJECTIVETo analysis the differential expression of decidua tissue proteins and effective mechanisms of recurrent abortion mice with Shoutai Wan, and explore the mechanism of Shoutai Wan in preventing miscarriage.

METHODThe abortion-prone CBA/J x DBA/2 matings were established as the model of recurrent abortion and the nonabortion-prone CBA/J x BALB/c matings were used as the model of normal pregnancy. The model of recurrent abortion CBA/J x DBA/2 of mice pregnant were randomly divided into four groups according to the sequence of pregnancy, including model group, Shoutai Wan low-dose group, Shoutai Wan middle-dose group and Shoutai Wan high-dose group. From the 1st day of pregnant, mice of normal group, model group, Shoutai Wan low-dose group (3 g x kg x d(-1)), Shoutai Wan middle-dose group (6 g x kg x d(-1)) and Shoutai Wan high-dose group (12 g x kg x d(-1)) are oral administration in different doses. On the 14th day of pregnancy, all mice are killed and the embryo loss rate (ELR) was counted. The expression of differential proteins of mice decidua tissues were separated by means of 2-DE and identified by MALDI-TOF-MS. The functions of identified proteins were further analysed according to bioinformatics resources.

RESULTCompared with model group, low-dose Shoutai Wan can not significantly improve the model of recurrent abortion in pregnant mice ELR; Shoutai Wan middle-dose and high-dose group of pregnant mice ELR were significantly decreased (P < 0.01). The results showed that the well-resolved, reproducible 2-DE patterns of mice decidua tissues of model group, normal group and Shoutai Wan low middle high-dose group were obtained. Through comparative proteome analysis of decidua tissues of all groups, 30 differential expression protein spots which maybe related to recurrent abortion and Shoutai Wan intervention were identified by MALDI-TOF-MS. These differential expression proteins mainly refer to invasion of the blastocyst, blood vessel remodeling and cell apoptosis.

CONCLUSIONShoutai Wan can decrease recurrent abortion mice ELR significantly, and play a role in preventing miscarriage. Recurrent abortion is a complicated process refer to diverse proteins participate. For several protein spots expression of decidua tissues in recurrent abortion mice was regulated by Shoutai Wan, it provides contribution to the effect characteristic of multitarget.

Abortion, Habitual ; metabolism ; pathology ; prevention & control ; Animals ; Decidua ; drug effects ; metabolism ; pathology ; Drugs, Chinese Herbal ; pharmacology ; Female ; Mice ; Pregnancy ; Proteome ; metabolism

BACKGROUNDThe management of patients with recurrent miscarriage (RM) and antiphospholipid antibody syndrome (APS) includes prolonged treatment with heparin and aspirin, starting from the confirmation of pregnancy and continuing until 6 weeks after birth. This study was conducted to determine the relationship between changes in antiphospholipid antibody titers and clinical outcomes. The effect of a shortened treatment regimen was also evaluated.

METHODSA prospective study of 123 patients with RM and APS between March 2012 and May 2014 was conducted. Patients were pretreated with a low dose of prednisone plus aspirin before pregnancy, and heparin was added after conception. The levels of antiphospholipid antibodies and pregnancy outcomes were evaluated.

RESULTSAll patients were positive for anti-β2-glycoprotein 1 (anti-β2-GP1) IgM. After prepregnancy treatment with low-dose prednisone plus aspirin, 99 of 123 patients became pregnant, and 87 of those pregnancies resulted in successful live births, while 12 resulted in miscarriage, showing a success rate of 87.9%. In the live birth group, levels of anti-β2-GP1 were 56.8 ± 49.0 RU/ml before the pretreatment regimen, 32.1 ± 26.0 RU/ml after 2 months of pretreatment, and 24.1 ± 23.1 RU/ml during early pregnancy (P < 0.05). In the miscarriage group, antiphospholipid antibody titers were 52.8 ± 30.7 RU/ml before pretreatment, 38.5 ± 34.2 RU/ml after pretreatment, and 33.9 ± 24.7 RU/ml during early pregnancy; the decrease in antiphospholipid antibodies was lower in the miscarriage group than in the live birth group (P < 0.05). Of the 24 infertile patients, the average antibody titer did not decline after pretreatment (P = 0.802).

CONCLUSIONSAnti-β2-GP1 IgM was the predominant form of antibody in patients with RM and APS. The decreases in antiphospholipid antibody titers correlated with better pregnancy outcomes. The shorter treatment regimen was effective and economical.

Abortion, Habitual ; immunology ; prevention & control ; Adult ; Antibodies, Antiphospholipid ; immunology ; Anticoagulants ; therapeutic use ; Antiphospholipid Syndrome ; drug therapy ; immunology ; Aspirin ; therapeutic use ; Female ; Heparin ; therapeutic use ; Humans ; Live Birth ; Prednisone ; therapeutic use ; Pregnancy ; Pregnancy Complications ; prevention & control ; Pregnancy Outcome ; Prospective Studies

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