A Ribeiro1,2,3, C Freitas4, L Matos5,6,7, A Gouveia5,6,7, F Gomes8,9, J L Silva Carvalho8,5,10,9, H Almeida5,6,9. 1. Centro de Estudo e Tratamento da Infertilidade (CETI), 4100-118, Porto, Portugal. angela.ribeiro@ceti.pt. 2. IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Instituto de Investigação e Inovação em Saúde - i3S, Universidade do Porto, 4200-135, Porto, Portugal. angela.ribeiro@ceti.pt. 3. Biomedicine Department, Faculty of Medicine, University of Porto, 4200-319, Porto, Portugal. angela.ribeiro@ceti.pt. 4. Reprodutive Medicine, Obstetrics and Gynecology, Hospital Dr. Nélio Mendonça, SESARAM, 9004-541 Funchal, Portugal; Obstetrics-Gynecology Department, University of Porto, Porto, Portugal. 5. IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Instituto de Investigação e Inovação em Saúde - i3S, Universidade do Porto, 4200-135, Porto, Portugal. 6. Biomedicine Department, Faculty of Medicine, University of Porto, 4200-319, Porto, Portugal. 7. Faculty of Nutrition and Food Sciences, University of Porto, 4200-465, Porto, Portugal. 8. Centro de Estudo e Tratamento da Infertilidade (CETI), 4100-118, Porto, Portugal. 9. Obstetrics-Gynecology, Hospital CUF Porto, 4100-180, Porto, Portugal. 10. Obstetrics-Gynecology Department, University of Porto, 4200-319, Porto, Portugal.
Abstract
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.
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.
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