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RHAMM deficiency disrupts folliculogenesis resulting in female hypofertility.

Li H, Moll J, Winkler A, Frappart L, Brunet S, Hamann J, Kroll T, Verlhac MH, Heuer H, Herrlich P, Ploubidou A - Biol Open (2015)

Bottom Line: This resulted in folliculogenesis defects and female hypofertility, although HA-induced signalling was not affected.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.

View Article: PubMed Central - PubMed

Affiliation: Leibniz Institute for Age Research - Fritz Lipmann Institute, Beutenbergstrasse 11, D-07745 Jena, Germany.

No MeSH data available.


Related in: MedlinePlus

RHAMM mRNA expression and localization in the mouse ovary and uterus.(A) Representative section of the female reproductive organs, subjected to radioactive in situ hybridization, reveals strong expression of RHAMM along the (mitotic) epithelium of the uterus glands and in ovarian follicles of different maturation stages, visualised on an X-ray film autoradiogram. (B,C) RHAMM expression in the ovarian follicles is restricted to the proliferative granulosa cells (GCs) surrounding the oocyte, as illustrated by dark-field illumination of Cresyl-violet counterstained ovary sections. Consistent with this, the highest expression, as indicated by labelling intensity, is observed in secondary follicles containing highly proliferative GCs (arrow) and it is decreased in antral follicles (arrowhead) concomitantly with the decreased proliferation of GCs in these follicles. (D,E) Magnification showing the labelling along the epithelium of the uterus glands. Scale bars: 5 mm (A); 5 µm (B,D).
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f01: RHAMM mRNA expression and localization in the mouse ovary and uterus.(A) Representative section of the female reproductive organs, subjected to radioactive in situ hybridization, reveals strong expression of RHAMM along the (mitotic) epithelium of the uterus glands and in ovarian follicles of different maturation stages, visualised on an X-ray film autoradiogram. (B,C) RHAMM expression in the ovarian follicles is restricted to the proliferative granulosa cells (GCs) surrounding the oocyte, as illustrated by dark-field illumination of Cresyl-violet counterstained ovary sections. Consistent with this, the highest expression, as indicated by labelling intensity, is observed in secondary follicles containing highly proliferative GCs (arrow) and it is decreased in antral follicles (arrowhead) concomitantly with the decreased proliferation of GCs in these follicles. (D,E) Magnification showing the labelling along the epithelium of the uterus glands. Scale bars: 5 mm (A); 5 µm (B,D).

Mentions: RHAMM expression had been detected previously in mRNA extracted from cattle cumulus-oocyte complexes (Schoenfelder and Einspanier, 2003), but its cell specific expression and localization in the reproductive system was unknown. We therefore analyzed RHAMM mRNA expression in the ovary and uterus of wild type mice by radioactive in situ hybridization. RHAMM mRNA was highly expressed along the mitotic epithelium of the uterus, as well as in distinct foci within the ovary that correspond to the ovarian follicles (Fig. 1A). RHAMM expression in the follicles was restricted to the proliferative granulosa cells surrounding the oocyte (Fig. 1B,C). The highest transcript levels were observed in secondary follicles containing highly proliferative granulosa cells (Fig. 1C, arrow) whereas lower hybridization signal intensities were found in follicles with growing antrum (Fig. 1C, arrowhead), characterised by decreased granulosa cell proliferation.


RHAMM deficiency disrupts folliculogenesis resulting in female hypofertility.

Li H, Moll J, Winkler A, Frappart L, Brunet S, Hamann J, Kroll T, Verlhac MH, Heuer H, Herrlich P, Ploubidou A - Biol Open (2015)

RHAMM mRNA expression and localization in the mouse ovary and uterus.(A) Representative section of the female reproductive organs, subjected to radioactive in situ hybridization, reveals strong expression of RHAMM along the (mitotic) epithelium of the uterus glands and in ovarian follicles of different maturation stages, visualised on an X-ray film autoradiogram. (B,C) RHAMM expression in the ovarian follicles is restricted to the proliferative granulosa cells (GCs) surrounding the oocyte, as illustrated by dark-field illumination of Cresyl-violet counterstained ovary sections. Consistent with this, the highest expression, as indicated by labelling intensity, is observed in secondary follicles containing highly proliferative GCs (arrow) and it is decreased in antral follicles (arrowhead) concomitantly with the decreased proliferation of GCs in these follicles. (D,E) Magnification showing the labelling along the epithelium of the uterus glands. Scale bars: 5 mm (A); 5 µm (B,D).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4400598&req=5

f01: RHAMM mRNA expression and localization in the mouse ovary and uterus.(A) Representative section of the female reproductive organs, subjected to radioactive in situ hybridization, reveals strong expression of RHAMM along the (mitotic) epithelium of the uterus glands and in ovarian follicles of different maturation stages, visualised on an X-ray film autoradiogram. (B,C) RHAMM expression in the ovarian follicles is restricted to the proliferative granulosa cells (GCs) surrounding the oocyte, as illustrated by dark-field illumination of Cresyl-violet counterstained ovary sections. Consistent with this, the highest expression, as indicated by labelling intensity, is observed in secondary follicles containing highly proliferative GCs (arrow) and it is decreased in antral follicles (arrowhead) concomitantly with the decreased proliferation of GCs in these follicles. (D,E) Magnification showing the labelling along the epithelium of the uterus glands. Scale bars: 5 mm (A); 5 µm (B,D).
Mentions: RHAMM expression had been detected previously in mRNA extracted from cattle cumulus-oocyte complexes (Schoenfelder and Einspanier, 2003), but its cell specific expression and localization in the reproductive system was unknown. We therefore analyzed RHAMM mRNA expression in the ovary and uterus of wild type mice by radioactive in situ hybridization. RHAMM mRNA was highly expressed along the mitotic epithelium of the uterus, as well as in distinct foci within the ovary that correspond to the ovarian follicles (Fig. 1A). RHAMM expression in the follicles was restricted to the proliferative granulosa cells surrounding the oocyte (Fig. 1B,C). The highest transcript levels were observed in secondary follicles containing highly proliferative granulosa cells (Fig. 1C, arrow) whereas lower hybridization signal intensities were found in follicles with growing antrum (Fig. 1C, arrowhead), characterised by decreased granulosa cell proliferation.

Bottom Line: This resulted in folliculogenesis defects and female hypofertility, although HA-induced signalling was not affected.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.

View Article: PubMed Central - PubMed

Affiliation: Leibniz Institute for Age Research - Fritz Lipmann Institute, Beutenbergstrasse 11, D-07745 Jena, Germany.

No MeSH data available.


Related in: MedlinePlus