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Revisiting germ cell dynamics and ovarian follicle assebly in the mouse model
Publication . Rodrigues, Patrícia Carla Coelho, 1973-; Santos, Carlos Eugénio Plancha dos, 1960-; Albertini, David F.
Development of the mammalian ovary is characterized by extensive germ cell loss and the retention of a subset of germ cells within the primordialm follicle reserve. Here we aimed to identify the mechanisms whereby some germ cells are retained while others are lost using novel imaging techniques and animal models. We observed that multiple mechanisms contributed to germ cell loss at birth. Our results confirmed germ cell loss around birth of approximately 44%, but our apoptotic numbers did not account to all that loss. Besides non-apoptotic germ cell loss through the ovarian surface, the use of serum cultured ovaries, and selective autophagy and apoptosis inhibitors, allowed us to suggest other cell death mechanism besides apoptosis may be involved in follicular reserve establishment around birth. To investigate germ-somatic cell interactions during ovarian follicle assembly, antibodies against cytoskeleton, extracellular matrix (ECM), and intercellular junctions were used to track expression patterns by immunofluorescence. We could confirm that a true ovarian epithelium is not formed until day 20 after birth. The persistence of gap junctions throughout ovary development implies that ovarian follicle reserve establishment requires an ongoing dialogue between somatic and germ cells. To better understand this cellular dialogue, we used four mouse models with specific gene deletion: GDF9 (growth differentiation factor 9), Nobox (newborn ovary homeobox gene), Sohlh1 (sperma-and oogenesis basic helix-loop-helix1), and FSHβ (follicle stimulating hormone). We found deficient gap junction communication between germ somatic cells in the FSHβ and GDF9 models, as well as specific cytoskeletal and ECM modifications in all models. In conclusion both oocyte-intrinsic (GDF9, Nobox, Sohlh1) and ovary extrinsic (FSHβ) factors differentially modulate germ-somatic cell interactions during ovarian development, influencing follicle assembly and ovarian follicle reserve establishment.

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Fundação para a Ciência e a Tecnologia

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SFRH

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SFRH/BD/6439/2001

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