RHAMM deficiency disrupts folliculogenesis resulting in female hypofertility

Biology Open
Huaibiao LiAspasia Ploubidou

Abstract

The postnatal mammalian ovary contains the primary follicles, each comprising an immature oocyte surrounded by a layer of somatic granulosa cells. Oocytes reach meiotic and developmental competence via folliculogenesis. During this process, the granulosa cells proliferate massively around the oocyte, form an extensive extracellular matrix (ECM) and differentiate into cumulus cells. As the ECM component hyaluronic acid (HA) is thought to form the backbone of the oocyte-granulosa cell complex, we deleted the relevant domain of the Receptor for HA Mediated Motility (RHAMM) gene in the mouse. This resulted in folliculogenesis defects and female hypofertility, although HA-induced signalling was not affected. We report that wild-type RHAMM localises at the mitotic spindle of granulosa cells, surrounding the oocyte. Deletion of the RHAMM C-terminus in vivo abolishes its spindle association, resulting in impaired spindle orientation in the dividing granulosa cells, folliculogenesis defects and subsequent female hypofertility. These data reveal the first identified physiological function for RHAMM, during oogenesis, and the importance of this spindle-associated function for female fertility.

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Citations

Jun 25, 2015·Frontiers in Immunology·Kathryn L SchwertfegerJames B McCarthy
Nov 2, 2016·Reproduction : the Official Journal of the Society for the Study of Fertility·Ali A Fouladi-NashtaGeraldine M Hartshorne
Dec 26, 2018·Molecular Carcinogenesis·Huaibiao LiAspasia Ploubidou
Dec 18, 2018·Frontiers in Immunology·Pauline JohnsonYifei Dong

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Methods Mentioned

BETA
X-ray
phosphotransferase
biopsies
genotyping

Software Mentioned

Cell
Adobe Photoshop
Metamorph
ImageJ

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