ORIGINAL ARTICLE: Bcl‐2 and Bax Expressions in Pre‐Term, Term and Post‐Term Placentas

American Journal Of Reproductive Immunology (Impact Factor: 3.32). 07/2008; 60(2):172 - 178. DOI: 10.1111/j.1600-0897.2008.00609.x

ABSTRACT Problem  Placental apoptosis-associated protein imbalance might contribute to the pathogenesis of pre- and post-term birth. Therefore, we evaluated the expression and distribution of pro-apoptotic (Bax) and anti-apoptotic (Bcl-2) molecules in term, pre-term and post-term placentas.Method of study  Placental samples were collected from women with term (n = 25), pre-term (n = 7) and post-term (n = 10) deliveries. The expression of Bcl-2 and Bax was assessed by immunochemistry on paraffin-embedded placental specimens.Results  The pattern of immunostaining for Bcl-2 and Bax was the same in all samples, but not the intensity. The Bax/Bcl-2 ratio was higher in both pre-term and post-term placental samples compared with term placentas as a result of intense reactivity for the pro-apoptotic factor, Bax in pre-term and post-term placentas and, for Bcl-2 decrease in pre-term placentas.Conclusion  These findings suggest that different unbalance mechanisms in placental apoptotic-associated protein expressions may be involved in the physiopathology of pre-term and post-term births.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Apoptosis plays a central role in organ development, homeostasis and immune defence in multicellular organisms and is strictly controlled in part by members of Bcl-2 family. The Bcl-2 is a pro-survival molecule identified through its involvement in B-cell lymphomas. The aim of the study was to evaluate the incidence of apoptosis in the human placenta at different stages of pregnancy and to correlate it further with Bcl-2 expression. A total of 96 placental samples from first trimester, mid-trimester and uncomplicated term pregnancies were collected (n = 32 + 32 + 32). M30 cyto death monoclonal antibody was used to identify apoptotic cells. The apoptosis index of first trimester placentae was 2.33 ± 1.70, mid- trimester was 1.77 ± 1.36 and term placenta was 1.15 ± 0.21. Bcl-2 protein was found immunolocalized in the cytoplasm of syncytiotrophoblast. Apoptosis index was significantly reduced in term cases as compared with first trimester (P < 0.002) and mid-trimester placentae (P = 0.01). On the contrary, Bcl-2 expression was significantly higher at term cases than in first trimester (P < 0.0001) and mid-trimester cases (P < 0.001). The present study divulges the importance of apoptosis in permitting normal physiological turnover of villous trophoblast and also exhibits the contribution of bcl-2 in maintaining syncytial integrity throughout normal pregnancy.
    Anantomia Histologia Embryologia 07/2010; 39(5):426-31. · 0.88 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The endocrine disruptor 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been demonstrated to disrupt hormone signalling, reduce fertility, interfere with embryo development and cause spontaneous miscarriage in humans. The precise mechanisms of its effects on early implantation in humans are still unclear. In this study, we examined the relationship between mitochondrial function and dioxin-induced toxicity in JAR cells, a human trophoblast-like cell line. Several experiments were performed to address the effects of TCDD on cell viability, reactive oxygen species (ROS) generation, oxidative damage (indicated by the presence of lipoperoxides and oxidized DNA bases), mitochondrial DNA (mtDNA) copy number, ATP content, mtDNA mutations and the protein levels of p53, Bax, Bcl2, cytochrome c and caspase 3. Increased oxidative damage and mitochondrial dysfunction in TCDD-treated trophoblast-like cells was demonstrated. A 2.58-fold increase in lipid peroxides was detected in cells treated with 2 nM TCDD for 4 h. The oxidative DNA damage marker 8-hydroxy-2'-deoxyguanosine was significantly increased by TCDD treatment in a time-dependent manner. Meanwhile, reductions in mtDNA copy number and ATP content and an increase in mtDNA deletions were found. Furthermore, we observed increased apoptosis, p53 accumulation, Bax overexpression, cytochrome c release and sequential caspase 3 activation after TCDD exposure. These results indicate that oxidative damage and mitochondrial dysfunction may be responsible for the apoptotic effects of TCDD.
    Molecular Human Reproduction 05/2010; 16(5):361-72. · 4.54 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Pregnancy is thought to be a state of immunological tolerance. The mechanisms underlying this phenomenon are still poorly understood. In our previous study, adenovirus mediated CTLA4Ig transgene (Ad-CTLA4Ig) therapy was demonstrated to improve pregnancy outcome in an abortion-prone mouse model by skewing the Th2/Th1 cytokine balance, expanding peripheral CD4(+) CD25(+) regulatory T cell populations and inducing indoleamine 2,3 dioxygenase (IDO) mRNA expression at the maternal-fetal interface. However, it is still not clear whether other mechanisms are involved in the protective effect of CTLA-4 on pregnancy outcome in abortion-prone matings. In this study, we focused on the effect of CTLA4Ig on spleen lymphocyte proliferation and apoptosis at the maternal-fetal interface. We demonstrated that Ad-CTLA4Ig therapy inhibited the proliferation of CBA/J splenocytes and IL-2 secretion in response to DBA/2 stimulator cells in the abortion-prone mice model. Ad-CTLA4Ig therapy also skewed cytokine production toward a Th2 bias and regulated the expression of anti-apoptosis factor Bcl-2 and pro-apoptosis factor Bax at the maternal-fetal interface. However, it did not influence the apoptosis and cell cycles of splenocytes in pregnant CBA/J mice. On the whole, these findings indicated that Ad-CTLA4Ig therapy could ameliorate the outcome of spontaneous abortion by inhibiting proliferation of maternal spleen lymphocytes and regulating apoptosis in the feto-placental unit.
    Journal of Reproductive Immunology 02/2013; · 2.34 Impact Factor