Normal expression of isoforms activating cyclic adenosine monophosphate responsive element modulator in patients with spermatid maturation arrest.

OBJECTIVE: To evaluate whether defective cyclic adenosine monophosphate responsive element modulator (CREM) expression is the causative factor of spermatid maturation arrest (SMA). DESIGN: Comparative evaluation of the testicular histology in patients with SMA or normal spermatogenesis. SETTING: University clinic of andrology. PATIENT(S): Azoospermic patients undergoing testicular biopsy. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Expression of CREMtau in quantitative immunohistochemistry analysis of testicular biopsy samples. RESULT(S): Regular CREM expression was observed in the tubules with round, but not elongated, spermatids of patients with SMA (n = 9). Quantitative analysis showed that round spermatids of patients with SMA had a staining intensity similar to that observed in controls (n = 7). CONCLUSION(S): Lack of spermatid elongation was not due to defective CREM expression. Therefore, CREM did not play a pathogenetic role in the onset of SMA in humans.

Expression of alpha(v)beta3 and alpha4beta1 integrins throughout the putative window of implantation in a cohort of healthy fertile women.

BACKGROUND: Blastocyst implantation is a dynamic process requiring a specific cascade of cellular interactions and endometrial changes. The aim of this prospective observational study was to investigate the endometrial expression of alpha(v)beta3 and alpha4beta1 integrins throughout the window of implantation in healthy fertile women. MATERIALS AND METHODS: Forty fertile women (mean age 29.7 +/- 6.2 years) were recruited for this study. All underwent two endometrial biopsies in a single menstrual cycle. The first biopsy was performed on postovulatory day 6, while the second was taken on postovulatory day 8. Histological dating and immunohistochemical assessments of alpha(v)beta3 and alpha4beta1 integrins were analyzed. Oestradiol and progesterone serum concentrations were also measured at the time of biopsy. RESULTS: Second endometrial biopsy could not be performed in two of the 40 women (5%) because their menses had started in advance. No inflammatory or reactive phenomena were observed after biopsy. All the samples showed an in-phase endometrium. alpha(v)beta3 integrin expression was found in 21 out of the 38 first biopsies and in all 38 second biopsies (55.2% vs. 100%, p < 0.001). alpha4beta1 integrin expression was not significantly different between first and second biopsies (68.4% and 76.3%, NS). Oestradiol and progesterone serum concentrations were similar throughout the implantation window. Twelve of the 38 women (31.6%) conceived within 12 months of completing the study. All these had significantly higher alpha(v)beta3 integrin expressions in mid-luteal phase biopsies compared with those who did not conceive. CONCLUSIONS: These immunohistochemical findings demonstrate that both alpha(v)beta3 and alpha4beta1 integrins have a spatial and temporal expression throughout the implantation window in the endometrium of fertile women. Moreover, the shortage of alpha(v)beta3 integrin expression during the mid-luteal phase results in a detrimental effect for blastocyst implantation.