Hippo signaling, actin polymerization, and follicle activation in fragmented human ovarian cortex

Stine A Lunding, Anders N Andersen, Lilja Hardardottir, Hanna Ø Olesen, Stine G Kristensen, Claus Y Andersen, Susanne E Pors

    24 Citations (Scopus)

    Abstract

    The Hippo pathway has been associated with regulation of early follicle growth. Studies of murine ovaries suggest that changes in the actin cytoskeleton, caused by fragmentation, result in inhibition of the Hippo pathway, and in turn, may activate follicle growth. In humans, the connections between fragmentation, the actin cytoskeleton, and follicle activation are yet to be confirmed. In this study, we investigated the impact in vitro fragmentation of a human ovarian cortex on (a) actin polymerization, (b) components of the Hippo pathway, and (c) follicle growth in vivo. The results showed that the ratio between globular and filamentous actin remained unchanged at all timepoints (0, 10, 30, 60, 120, and 240 min) following tissue fragmentation. Neither was the Hippo pathway effector protein YES-associated protein upregulated nor was gene expression of the downstream growth factors CCN2, CCN3, or CCN5 increased at any timepoint in the fragmented cortex. Furthermore, the number of growing follicles was similar in fragmented and intact cortex pieces after 6 weeks' xenotransplantation. However, the total number of surviving follicles was considerably lower in the fragmented cortex compared with intact tissue, suggesting detrimental effects of fragmentation on tissue grafting. These results indicate that fragmentation is likely to be ineffective to activate follicle growth in the human ovarian cortex.

    Original languageEnglish
    JournalMolecular Reproduction and Development
    Volume87
    Issue number6
    Pages (from-to)711-719
    Number of pages9
    ISSN1040-452X
    DOIs
    Publication statusPublished - Jun 2020

    Keywords

    • actin
    • female infertility
    • follicle activation
    • Hippo pathway
    • ovarian cortex

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