Małgorzata Jerzak

Apoptosis in the first trimester human placenta: the role in maintaining immune privilege at the maternal–foetal interface and in the trophoblast remodelling

Apoptosis has been proposed as a mechanism for maintaining immune privilege. Expression of Fas ligand (FasL) by the human trophoblast has been recently accepted as a mechanism providing protection against the lytic action of activated decidual immune cells expressing Fas receptor (FasR). Therefore, the purpose of this review was to determine the role of apoptosis in early pregnancy maintenance according to the latest literature. We used Medline literature search. The data suggest that apoptosis may serve as a previously unsuspected mechanism that induces tolerance of the foetal allograft against maternal immune system. Apoptosis of activated maternal immune cells occurs in the human decidua mainly through Fas-FasL or receptor for TNF-related apoptosis-inducing ligand (TRAIL-R)-TNF-related apoptosis-inducing ligand (TRAIL) signalling. This might be a defence mechanism against rejection of the foetal allograft by the maternal immune system. In addition, in this review contribution of programmed cell death to placental cell turnover and remodelling during first trimester of pregnancy is also discussed.

Sildenafil citrate decreased natural killer cell activity and enhanced chance of successful pregnancy in women with a history of recurrent miscarriage.

OBJECTIVE To evaluate the effect of sildenafil on peripheral natural killer (NK) cell activity in women with a history of recurrent miscarriage (RM). DESIGN Observational study. SETTING University teaching hospital. PATIENT(S) Thirty-eight nonpregnant women with a history of RM and 37 healthy women with previous successful pregnancy outcomes. INTERVENTION(S) Patients self-administered sildenafil suppositories (25 mg intravaginally, four times a day) for 36 days. MAIN OUTCOME MEASURE(S) Peripheral blood NK-cell activity before and after vaginal sildenafil therapy in the RM women was measured using flow cytometry. In addition, the influence of 10 microg and 400 ng sildenafil on NK-cell activity after in vitro culture were determined. Uterine artery blood flow and endometrial thickness were recorded using Doppler ultrasound with an intravaginal probe. RESULT(S) The NK-cell activity was significantly decreased after vaginal sildenafil therapy. Endometrial thickness was significantly increased after such therapy. CONCLUSION(S) Vaginal sildenafil might be an interesting therapeutic option before conception in women with histories of reproductive failure.

First Successful Pregnancy after Addition of Enoxaparin to Sildenafil and Etanercept Immunotherapy in Woman with Fifteen Failed IVF Cycles – Case Report

Citation Jerzak M, Niemiec T, Nowakowska A, Klochowicz M, Górski A, Baranowski W. First successful pregnancy after addition of enoxaparin to sildenafil and etanercept immunotherapy in woman with fifteen failed in vitro fertilization (IVF) cycles – case report. Am J Reprod Immunol 2010; 64: 93–96

The Influence of Extracellular Matrix Proteins on T-cell Proliferation and Apoptosis in Women with Endometriosis or Uterine Leiomyoma

Problem:  Interactions between the extracellular matrix (ECM) and peripheral blood T cells in women with endometriosis and leiomyoma are hardly unknown. We have investigated the influence of two major ECM components, collagen IV (C‐IV) and fibronectin (Fn), on T‐cell proliferation and apoptosis in women with endometriosis and uterine leiomyoma. β1 integrin expression, responsible for interactions with ECM proteins, was also studied.

Enhanced T cells interactions with extracellular matrix proteins in infertile women with endometriosis.

Essential features of endometriosis involve interactions with extracellular matrix (ECM). Recent data emphasize the important role of ECM proteins in the regulation of T cell function. The aim of this study was to determine activated T cell adhesion to ECM proteins in infertile women with endometriosis. Nine women with endometriosis diagnosed by laparoscopy according to the Revised American Fertility Society classification and ten normal healthy women with a previous successful pregnancy outcome were studied. We investigated phorbol acetate myristate (PMA) or phytohemaglutinin (PHA) activated peripheral blood T cell adhesion to the following proteins of ECM: collagen IV (C-IV), elastin (E) and fibronectin (Fn). In addition, CD4, CD8, CD29, CD45RO expression on peripheral CD3(+) T cells were studied using flow cytometry. We determine that PHA-activated T cell adhesion to C-IV and Fn are significantly higher in infertile women with endometriosis when compared to normal healthy women (P<0.05). No significant differences were noted in T cells surface antigens expression between study groups. Our data suggest the existence of disturbed T cell-ECM interactions in infertile women with endometriosis. Further studies are needed to determine the role of these abnormalities in the pathogenesis of endometriosis.

Ectopic and eutopic stromal endometriotic cells have a damaged ceramide signaling pathway to apoptosis

OBJECTIVE To investigate whether sphingosine analogues, which activate the ceramide signaling pathway to apoptosis, can cause the death of ectopic (EEC) and eutopic stromal endometriotic cells (EEU), as well as healthy eutopic stromal endometrial cells (HEU). DESIGN The EEC, EEU, and HEU isolated from fertile and infertile women with endometriosis were cultured for 48 hours in RPMI medium with 10% fetal calf serum (FCS) and with 2.5-10 microM sphingosine analogues. SETTING A clinic for the treatment of endometriosis and basic research laboratories. PATIENT(S) Nineteen women with follicular cyst and 16 women with endometriosis. MAIN OUTCOME MEASURE(S) The percentage of proliferating cells was determined by 93-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) assay. Apoptosis and cell cycle were detected by fluorescence-activated cell sorter (FACS) Calibur flow cytometer. RESULT(S) The viability of EEC after exposure to 10 microM sphingosine analogues was 59.5% +/- 9.7% for D-sphingosine and 77.65 +/- 9.7% for DL-erythro-sphingosine, the viability of EEU was 69.2% +/- 14.2% and 42.0% +/- 15.5%, whereas the viability of comparative HEU was 9.0% +/- 4.8% and 18.8% +/- 8.3%, respectively. The differences were significant using the Mann-Whitney test. The apoptotic level of the cells treated with 10 microM sphingosine analogues for comparative HEU was 42.8% +/- 7.5% for D-sphingosine and 42.5% +/- 10.5% for DL-erythro-sphingosine, whereas for EEC this was 16.7% +/- 5.5% for D-sphingosine and 14.1% +/- 4.4% for DL-erythro-sphingosine and for EEU this was 14.3% +/- 4.7% and 22.9% +/- 8.9%, respectively. CONCLUSION(S) Ectopic and eutopic stromal endometrial cells from women with endometriosis have a damaged ceramide-downstream pathway to apoptosis.

Survivin expression as a prognostic factor in patients with epithelial ovarian cancer or primary peritoneal cancer treated with neoadjuvant chemotherapy.

Background The aim of this study was to evaluate association of expression of survivin and p53 with the effects of neoadjuvant chemotherapy (NAC) in patients with advanced ovarian cancer (AOC). Methods We retrospectively evaluated 60 consecutive patients with AOC (International Federation of Gynecology and Obstetrics stage IIIC-IV) treated with NAC. The expression of p53 and survivin was assessed immunohistochemically. The median of expression total score survivin equals 2 was adopted to dichotomize the group. The positive and negative expression of p53 was used to dichotomize the group. Results The expression of survivin in tumor tissue taken before and after NAC was a significant difference in the percentage of stained nuclei (P = 0.0002), the intensity of staining (P = 0.0003), and total score (P = 0.0001). There was a significant difference in p53 expression in tumor tissue before and after NAC in the percentage of stained nuclei (P = 0.0424). Survivin expression, in contrast to p53 expression, was a prognostic factor in patients with AOC treated with NAC (P = 0.0484). The expression of survivin and p53 was not a predictive factor. Independent adverse predictor factors were as follows: lack of optimal interval debulking surgery and the lack of an objective response (the respective hazard ratio was 3.93 [95% confidence interval, 2.07–7.46; P < 0.0001] and 2.36 [95% confidence interval,1.25–4.47; P = 0.0080]). The suboptimal range of interval debulking surgery, resistance to platinum, and the lack of paclitaxel in the NAC were adverse prognostic factors (the respective hazard ratio was 2.61 [95% confidence interval, 1.17–5.83], 2.72 [95% confidence interval, 1.07–6.89], and 2.56 [95% confidence interval, 1.06–6.18]; P < 0.05]). Conclusions High expression of survivin could be a prognostic factor in patients treated with NAC for AOC.

Reliability and clinical validity of a Polish version of the CONTILIFE: a quality of life questionnaire for urinary incontinence

Introduction and hypothesisThe primary aim of the study was to translate and validate a Polish version of the CONTILIFE, a quality of life questionnaire. The clinical validity of the CONTILIFE was assessed against the number of urinary leaks, Valsalva leak point pressure (VLPP), and maximum urethral closure pressure (MUCP).MethodsOne hundred women with stress urinary incontinence completed a Polish version of the CONTILIFE twice with a 4-day interval.ResultsInternal consistency (Cronbach’s α= 0.94) and test–retest reliability of the instrument (ICC = 0.96) were very good. A significant relationship was found between all the CONTILIFE dimension scores, the CONTILIFE global score, and the number of urinary leaks per week. A less significant relationship was found between VLPP, MUCP, and CONTILIFE dimension and global scores.ConclusionsA Polish version of the CONTILIFE can be a reliable measure of quality of life in stress urinary incontinence patients.

Extracellular Matrix Protein‐dependent Apoptosis of T Cells in Women with a History of Recurrent Spontaneous Abortion

Problem:  The purpose of the study was to determine the role of T‐cell apoptosis in extracellular matrix (ECM) environment in pregnancy maintenance in women with a history of recurrent spontaneous abortion (RSA).