Dexamethasone attenuates the embryotoxic effect of endometriotic peritoneal fluid in a murine model.

PURPOSE: The in vitro fertilization (IVF) pregnancy rate of women with advanced stage endometriosis is nearly half that of the general population, suggesting incomplete targeting of the pathophysiology underlying endometriosis-associated infertility. Compelling evidence highlights inflammation as the etiologic link between endometriosis and infertility and a potential target for adjunctive treatment. The objective of this study was to examine the effect of dexamethasone on murine embryos exposed to human endometriotic peritoneal fluid (PF) using the established murine embryo assay model. METHODS: PF was obtained from women with and without severe endometriosis. Murine embryos were harvested and randomly allocated to five groups of culture media conditions: (1) human tubal fluid (HTF), (2) HTF and 10 % PF from women without endometriosis, (3) HTF and 10 % PF from women with endometriosis (PF-E), (4) HTF with PF-E and 0.01 mcg/mL dexamethasone, and (5) HTF with PF-E and 0.1 mcg/mL dexamethasone. Embryos were cultured in standard conditions and evaluated for blastocyst development. RESULTS: A total of 266 mouse embryos were cultured. Baseline blastulation rates were 63.6 %. The addition of peritoneal fluid from women with endometriosis decreased the blastocyst development rate to 38.9 % (P = 0.008). The addition of 0.1 mcg/mL of dexamethasone to the culture media restored the blastulation rate to near baseline levels (61.2 %; P = 0.019). CONCLUSIONS: The results of our in vitro study demonstrate the capacity of dexamethasone to mitigate the deleterious impact of endometriotic PF on embryo development. If confirmed in vivo, dexamethasone may prove a useful adjunct for the treatment of endometriosis-associated infertility.

Effect of cigarette smoking on human oviductal ciliation and ciliogenesis.

OBJECTIVE: To investigate the effect of cigarette smoke exposure on ciliation and ciliogenesis in human oviductal epithelium. DESIGN: Molecular analysis using human tubal segments. SETTING: Academic medical center. PATIENT(S): Twenty women undergoing elective tubal sterilization procedure. INTERVENTION(S): Expression of ciliated cell-specific markers was compared in tubal segments from smokers and nonsmokers using quantitative immunohistochemistry and Western blot analysis. The expression of transcription factors in the motile ciliogenesis program was compared using quantitative polymerase chain reaction and quantitative immunohistochemistry. MAIN OUTCOME MEASURE(S): Oviductal ciliation and expression of transcription factors involved in ciliogenesis. RESULT(S): No significant differences were detected in density of ciliation between groups. Neither number of years of smoking nor pack-year history correlated with density of ciliation. Expression of ciliogenic transcription factors FOXJ1, RFX2, and RFX3 was consistent between groups. CONCLUSION(S): Few studies have evaluated the relationship between smoking and ciliated epithelium in human oviducts. Cigarette smoking does not seem to result in quantitative differences in the density of ciliation nor expression of ciliogenesis factors. Our findings suggest that pathophysiologic mechanisms other than ciliation account for the increased risk of ectopic pregnancy in women who smoke.

Frequency of epitope-specific naive CD4(+) T cells correlates with immunodominance in the human memory repertoire.

The frequency of epitope-specific naive CD4(+) T cells in humans has not been extensively examined. In this study, a systematic approach was used to examine the frequency of CD4(+) T cells that recognize the protective Ag of Bacillus anthracis in both anthrax vaccine-adsorbed vaccinees and nonvaccinees with HLA-DRB1*01:01 haplotypes. Three epitopes were identified that had distinct degrees of immunodominance in subjects that had received the vaccine. Average naive precursor frequencies of T cells specific for these different epitopes in the human repertoire ranged from 0.2 to 10 per million naive CD4(+) T cells, which is comparable to precursor frequencies observed in the murine repertoire. Frequencies of protective Ag-specific T cells were two orders of magnitude higher in immunized subjects than in nonvaccinees. The frequencies of epitope-specific memory CD4(+) T cells in vaccinees were directly correlated with the frequencies of precursors in the naive repertoire. At the level of TCR usage, at least one preferred Vß in the naive repertoire was present in the memory repertoire. These findings implicate naive frequencies as a crucial factor in shaping the epitope specificity of memory CD4(+) T cell responses.