No abstract

Trophoblast rejection, which is characterized by increased apoptosis, is mediated by T helper (Th)-1, or proinflammatory, cytokines, whereas Th-2, or anti-inflammatory, cytokines confer immune protection and facilitate implantation. We investigated the role of both types of cytokines on the expression and function of the Fas/Fas ligand (FasL) apoptotic pathway in trophoblast cells. First-trimester human trophoblast primary-culture cells as well as A3 and HTR/8 trophoblast cell lines were treated with proinflammatory cytokines such as interferon-gamma (IFN-gamma) and tumor necrosis factor alpha (TNFalpha) and with the anti-inflammatory cytokines interleukin (IL)-6 and IL-10. Sensitivity to Fas-mediated apoptosis was measured using an activating anti-Fas monoclonal antibody. Cell viability was evaluated using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) and CellTiter 96 assay. Fas/FasL mRNA and protein expression levels were determined using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. Trophoblast cells normally express FasL, but low levels of Fas, and they are resistant to Fas-mediated apoptosis. IFN-gamma and TNFalpha promote Fas expression and sensitivity, whereas IL-6 and IL-10 increase the resistance of trophoblast cells to Fas-mediated apoptosis. Furthermore, IL-10 treatment activates FLICE-like inhibitory protein (FLIP), a downstream inhibitor of Fas apoptotic signaling. Although trophoblast cells express Fas, susceptibility to Fas does not necessarily correlate with its expression. In this study, we demonstrate that Th-2 cytokines increase the resistance of trophoblast cells to Fas-mediated apoptosis either by inhibiting Fas expression or by inducing FLIP activation. This "trophoblast-cytokine-Fas/FasL triad" determines the ability of the Fas/FasL system to regulate trophoblast viability and, consequently, the success or failure of pregnancy.

No abstract

Introduction A previous study demonstrated that women seeking treatment for advanced pelvic organ prolapsed (POP) reported decreased self-perceived body image and decreased quality of life. Aims To determine the relationship between: (i) sexual function and POP, (ii) self-perceived body image and POP; and (iii) sexual function and self-perceived body image in women with prolapse. Methods After IRB approval, consecutive women with POP stage II or greater presenting for urogynecologic care at one of eight academic medical centers in the United States were invited to participate. In addition to routine urogynecologic history and physical examination, including pelvic organ prolapse quantification (POPQ), consenting participants completed three validated questionnaires: Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) to assess sexual function; Modified Body Image Perception Scale (MBIS) to assess self-perceived body image; Prolapse subscale of Pelvic Floor Distress Inventory (POPDI-6) to assess condition specific bother from POP. Pearson’s correlations were used to investigate the relationship between independent variables. Main Outcome Measures Sexual function and modified body image score and its correlation with symptoms of POP. Results Three hundred eighty-four participants with a mean age of 62 ± 12 years were enrolled. Median POPQ stage was 3 (range 2–4). 62% (N = 241) were sexually active and 77% (N = 304) were post-menopausal. Mean PISQ-12, MBIS, and POPDI scores were (33 ± 7, 6 ± 5, 39 ± 23, respectively). PISQ-12 scores were not related to stage or compartment (anterior, apical, or posterior) of POP (P > 0.5). Worse sexual function (lower PSIQ-12 scores) correlated with lower body image perception (higher MBIS scores) (rho = −0.39, P < 0001) and more bothersome POP (higher POPDI scores) (rho = −0.34, P < 0001). Conclusions Sexual function is related to a woman’s self-perceived body image and degree of bother from POP regardless of vaginal topography. Sexual function may be more related to a woman’s perception of her body image than to actual topographical changes from POP.