Age-related expression of TGF beta family receptors in human cumulus oophorus cells.

PURPOSE: During ovarian follicle growth, local cellular interactions are essential for oocyte quality acquisition and successful fertilization. While cumulus cells (CCs) nurture oocytes, they also deliver oocyte-secreted factors (OSFs) that activate receptors on CCs. We hypothesized that disturbance of those interactions contributes to age-related lower reproductive success in women submitted to assisted reproductive technology treatments. METHODS: Women aged 27-48, without recognized personal reproductive disorder, were enrolled in the study and divided in <35- and ≥35-year-old groups. CCs collected upon follicle aspiration were processed for immunocytochemistry and RNA extraction. The expression patterns of OSF receptors BMPR2, ALK 4, ALK5, and activin receptor-like kinase (ALK6) were studied. RESULTS: Independently of age, receptors were found mostly in the cell periphery. The quantitative assay revealed that in older women, BMPR2, ALK 4, and ALK6 were all significantly decreased, whereas ALK5 was slightly increased. CONCLUSIONS: Female age imparts an effect on the expression of OSF receptors in CCs. The findings indicate that reproductive aging affects the local regulation of signaling pathways mediated by BMPR2, ALK6, and ALK4 receptor activation, suggesting their joint involvement.

Superoxide dismutase expression in human cumulus oophorus cells.

Success in assisted reproductive techniques (ART) is influenced by gamete and embryo quality but the assessment of these parameters has been thwarted by the lack of reliable biomarkers. Follicular fluid and cumulus oophorus cells may provide biomarkers due to their close relationship to the oocyte. These cells produce antioxidants and thus protect the oocyte from oxidative damage exerted by reactive oxygen species (ROS). ROS and antioxidants are known to intervene in reproductive physiology and pathology, but their roles are unclear. It is hypothesized that superoxide dismutase (SOD), a first line antioxidant enzyme, is associated with oocyte quality. Cells obtained in the course of ART for the treatment of infertility due to male factor or female pathology were processed for SOD intracellular isoforms (CuZnSOD and MnSOD) immunodetection, total SOD activity and isoforms content. Cells presented strong positive staining for CuZnSOD and MnSOD. SOD activity decreased with increasing female age but was increased in endometriosis and in ovulatory dysfunction. When male factor was the cause for infertility, successful ART was associated with higher SOD activity. Variations in SOD emphasize the relevance of oxidative stress in the oocyte maturation process. These variations also suggest that SOD is a potential biomarker for ART success.

Inter-observer agreement in analysis of basal body temperature graphs from infertile women.

In this study, we evaluated the reproducibility of analysis of basal body temperature graphs under optimized conditions for agreement. A total of 160 recordings were selected from spontaneous cycles of infertile women and analysed by three experienced clinicians using uniform criteria. Agreement at the various stages of analysis was assessed by the 'proportions of agreement' with 95% confidence intervals. Agreement in identification of the thermal nadir was clearly superior to that reported in previous publications. Reproducibility of 'ovulatory' graph features (i.e. biphasic graphs and adequate thermal shifts) was excellent. Agreement in classification of monophasic graphs and inadequate thermal shifts, although lower, was still good. Thus, with experienced observers and uniform criteria, a good agreement can be achieved in analysis of the most important parameters of the basal body temperature graph. We believe that an effort should be made to generalize the use of uniform analysis criteria, because only then can results from different institutions be compared and the remaining clinical evaluation of the method be performed.