IDO expression on decidual and peripheral blood dendritic cells and monocytes/macrophages after treatment with CTLA-4 or interferon-gamma increase in normal pregnancy but decrease in spontaneous abortion

Recent data demonstrated that CD4+CD25+ regulatory T (Treg) cells and an enzyme called indoleamine 2,3-dioxygenase (IDO) mediate maternal tolerance to the fetus. Interestingly, Treg cells express the CTLA-4 molecule on their surface, and B7 (CD80/86) ligation by CTLA-4 enhanced IDO activity of dendritic cells (DCs) and monocytes by the induction of interferon gamma (IFN-gamma) production. In this study, we studied the IDO expression on peripheral blood monocytes and decidual monocytes or DCs after treatment with CTLA-4/Fc fusion protein or IFN-gamma using flow cytometry. IDO expressions on both peripheral blood DC and decidual DC and monocytes were up-regulated during normal pregnancy. On the other hand, both IDO expression on DC and monocytes after IFN-gamma treatment or CTLA-4 treatment were decreased in spontaneous abortion cases. The expression of CD86 on peripheral blood and decidual monocytes and DC in spontaneous abortion cases was lower compared with those in normal pregnancy subjects. Also, IFN-gamma production by decidual and peripheral blood mononuclear cells after CTLA-4/Fc treatment in spontaneous abortion cases was significantly lower than those in normal pregnancy subjects. These data suggest that CTLA-4 on Treg cells up-regulates IDO expression on decidual and peripheral blood DC and monocytes by the induction of IFN-gamma production.     

Partial hydatidiform mole and hypertension associated with a live fetus--variable presentation in two cases

Partial hydatidiform mole associated with live births is a rarecondition. There are not enough cases in the literature to allowthe assessment of comprehensive risks to be made and upon whichmanagement policies can be based. Several clinical dilemmasarise following diagnosis of a viable pregnancy associated withmolar tissue. We present two cases demonstrating the problemsand suggest management based on outcome and a review of theliterature.     

妊娠期间脾脏T淋巴细胞的改变与鼠胚着床

应用ＦＩＴＣ标记的Ｌ３Ｔ４及Ｌｙ２单克隆抗体，及流式细胞计细胞分选，对小鼠妊娠期间脾脏Ｔ淋巴细胞亚群进行检测。结果表明，妊娠早期小鼠脾脏ＣＤ８＋淋巴细胞比例减少，在着床时尤为明显。提示脾脏Ｔ淋巴细胞数量和功能变化，参与维持正常妊娠，尤其是参与着床。     

Seroprevalence and incidence of Toxoplasma gondii infection in the Legnano area of Italy.

The decreasing prevalence of anti-Toxoplasma antibodies in Europe has re-opened the question of the appropriateness of serological screening during pregnancy. A study of 3426 pregnant women, resident in the Legnano area of Italy, revealed that the IgG seroprevalence according to ELISA was 21.5%, and that of IgM according to ELISA and enzyme-linked fluorescent assay was 1.2% and 0.9%, respectively. The incidence of infection, estimated on the basis of IgG avidity, was 0.9%. These results confirm a decrease in the prevalence of IgG, but indicate a high incidence of infection, thus suggesting that screening for anti-Toxoplasma antibodies during pregnancy should be maintained.     

Murine Trophoblast Failure and Spontaneous Abortion

PROBLEM: Infection has been proposed to initiate abortion, and the role of viruses in spontaneous resorption in mice has not been tested. METHOD: The anti-viral drug ribavirin (1-β-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) was fed to CBA/J and C3H/HeJ female mice beginning on the morning after mating with DBA/2J males. RESULTS: Ribavirin treatment increased the rate of abortion (resorption) on day 13.5, and this was associated with retardation of the rate of embryo development and hypoplasia of the trophoblast. There was a reduction in trophoblast-dependent decidua-associated soluble suppressor activity, but there was no maternal mononuclear cell infiltrate of the type reported in association with resorption of semiallogeneic and xenogeneic mouse embryos. This may be due to an immunosuppressive effect of ribavirin. Ribavirin was able to potently suppress proliferation of mouse trophoblast and mastocytoma cell lines in vitro. CONCLUSIONS: There are several drug-induced murine abortion models that provide useful insights into potential mechanisms underlying spontaneous pregnancy failure, but in the ribavirin model, a direct impairment of trophoblast development appears to be responsible.     

Termination of Pregnancy in Rodents by Oral Administration of Praneem,a Purified Neem Seed Extract

PROBLEM: Development of an orally administered abortifacient. METHODS: Subjects were female Wistar rats, weighting 150 to 200 g at the time of experiments. Praneem (a purified extract of neem Azadirachta indica) at a dose of 0.6 ml was given orally from day 8 to 10 after confirming presence and number of implants surgically on day 7 of pregnancy. The animals were examined again under anesthesia on day 15 of pregnancy to check the number of developing embryos. Controls received an equivalent regime of peanut oil. The number and size of implants were counted five days after treatment. RESULTS: Complete resorption of embryos was observed on day 15 of pregnancy in every animal treated with Praneem in contrast to normally developing embryos in rats given peanut oil. In repeat batch experiments, it was established that the effect of the treatment was reversible and animals regained fertility in cycles subsequent to treatment with Praneem. Cytokines of T_H1 type, i.e., gamma interferon and TNF, were raised on administration of Praneem, which may be the probable cause of pregnancy termination. CONCLUSIONS: Praneem on oral adminstration can cause termination of pregnancy in rodents, and the action is probably mediated by T_H1 cytokines.     

A Follow-up Study of Immunoglobulin Levels and Autobodies in an Unselected Pregnant Population

PROBLEM: To obtain a systematic view of changes in the levels of immunoglobulins (Igs), other serum proteins, and autoantibodies during pregnancy and postpartum. METHOD: A series of 220 women were followed throughout pregnancy and four to six months postpartum. RESULTS: Immunoglobulin G (IgG) concentration clearly decreased toward term. The concentrations of IgM and IgA decreased only slightly. In most instances autoantibody levels paralleled changes in the corresponding immunoglobulin class levels. In few cases, however, there were clear deviations from this. With respect to IgG class autoantibodies, the highest autoantibody levels were found in the postpartum specimen. IgM class autoantbody levels remained almost constant throughout the follow-up period. CONCLUSIONS: The intrapregnancy decrease of IgG is mainly due to hemodilution, but when the effect of hemodilution is taken into account, total amounts of IgM and IgA are increased. The results suggests that compared to IgG the regulatory mechanisms of IgM and IgA are altered during pregnancy.     

Sperm morphological assessment based on strict criteria and in-vitro fertilization outcome.

One-hundred-and-twenty-three in-vitro fertilization (IVF) cycles were analysed in order to clarify the influence of strictly normal morphology (SNM) of spermatozoa on IVF outcome. SNM was defined using strict criteria according to Kruger with our modifications. The IVF cycles studied were divided into three groups: %SNM less than 12% (13 cycles), 12 less than 40% (68 cycles), greater than or equal to 40% (42 cycles). The cleavage rates per oocyte were higher in the groups with 12-40% and greater than or equal to 40% of %SNM than in the group with %SNM less than 12%. The embryo transfer rate per cycle increased with increasing %SNM. The overall pregnancy rate per cycle increased with increasing %SNM (7.7% in %SNM less than 12%, 22.1% in 12-40% of %SNM, and 40.5% in %SNM greater than or equal to 40%). The ongoing pregnancy rate per cycle also increased with increasing %SNM (7.7% in %SNM less than 12%, 14.7% in 12-40% of %SNM, and 31.0% in %SNM greater than or equal to 40%). The miscarriage rate was lower in %SNM greater than or equal to 40% (23.5%) than in 12-40% of %SNM (33.3%). It was suggested that %SNM is a good predictor of IVF outcome.     

An algorithm to predict pregnancy in assisted reproduction

BACKGROUND: Male fertility potential cannot be measured by conventional parameters for the assisted reproduction technique; ICSI. This study determines the relationship between testicular and ejaculated sperm mitochondrial (mt) DNA deletions, nuclear (n) DNA fragmentation, and fertilization and pregnancy rates in ICSI. METHODS: Ejaculated sperm were obtained from 77 men and testicular sperm from 28 men with obstructive azoospermia undergoing ICSI. Testicular sperm were retrieved using a Trucut needle. mtDNA was analysed using a long PCR. The alkaline Comet assay determined nDNA fragmentation. RESULTS: Of subjects who achieved a pregnancy (50%) using testicular sperm, only 26% had partners' sperm with wild-type (WT) mtDNA. Of pregnant subjects (38%) using ejaculated sperm, only 8% had partner sperm with WT mtDNA. In each, the successful group had less mtDNA deletions and less nDNA fragmentation. There were inverse relationships between pregnancy and mtDNA deletion numbers, size and nDNA fragmentation for both testicular and ejaculated sperm. No relationships were observed with fertilization rates. An algorithm for the prediction of pregnancy is presented based on the quality of sperm nDNA and mtDNA. CONCLUSION: In both testicular and ejaculated sperm, mtDNA deletions and nDNA fragmentation are closely associated with pregnancy in ICSI.     

A twin-family study of self-report symptoms of panic-phobia and somatization

Self-report symptoms of anxiety are widely used in mental health and social science research as an index of current psychiatric state. Previous twin studies have suggested that genetic factors account for a significant proportion of the variance in these symptoms. To replicate and extend these findings, we examined self-report symtoms of panic-phobia and somatization in the “Virginia 30,000” twin-family sample. Model fitting applied to 80 unique relationships in the twin-family pedigree produced the following major results: (i) genetic effects were significant for both symptom factors, accounting for between 25 and 49% of the total variance, with the exception of symptoms of panic-phobia in females, where they accounted for 15–16% of the variance; (ii) familial environmental effects were absent for symptoms of somatization, while for symptoms of panic-phobia they accounted for a very small proportion of variance in males (≤1.2%) and a modest proportion in females (6–17%) (iii) spousal correlations were present for both factors, ranging from +0.05 to +0.20; (iv) genetic factors which influenced symptoms were generally the same in males and females, although their effect was greater in males; (v) heritability estimates were lower in the population-based than in the volunteer sample; and (vi) when test-retest reliability was included in the model, results suggest that genetic factors account for at least half of the stable variance for all symptom factors, except panic-phobia in females. Our results support the validity of previous twin studies of self-report symptoms of anxiety and suggest that genetic factors significantly influence these symptoms but familial-environmental factors play little or no etiologic role.