Biology of Reproduction, Vol 25, 599-608, Copyright © 1981 by Society for the Study of Reproduction

Regulation by Sulfated Glycosaminoglycans of the Expansion of Cumuli Oophori Isolated from Mice

¹ The Jackson Laboratory Bar Harbor, Maine 04609

Sulfated glycosaminoglycans (GAGs) inhibit the stimulatory effects of FSH on cumulus expansion and hyaluronic acid synthesis by oocyte-cumulus cell complexes isolated from mice. This paper reports experiments that begin an analysis of the mechanisms of this inhibition. The effects of sulfated GAGs on cumulus expansion and hyaluronic acid synthesis stimulated by cholera toxin, prostaglandin E₂ (PGE), and dibutyryl cyclic adenosine monophosphate (dbcAMP) were studied. The sulfated GAGs were very effective in inhibiting cumulus expansion and hyaluronic acid synthesis by cumuli oophori exposed to cholera toxin, PGE, and dbcAMP with relative potencies of heparin>heparan sulfate>chondroitin sulfate B (dermatan sulfate). Stimulation of expansion by cholera toxin or PGE was more readily inhibited by the sulfated GAGs than was stimulation by dbcAMP. Since the sulfated GAGs inhibited the effects of cholera toxin and PGE on cumulus expansion and hyaluronic acid synthesis, the action of the sulfated GAGs is not limited to, and may not entail, an interaction of FSH with its receptors. The finding that the sulfated GAGs inhibited stimulation by dbcAMP suggests that one target for the sulfated GAGs is some step after the generation of intracellular cAMP. Sulfated GAGs did not effect spontaneous oocyte meiotic maturation, the ultrastructural characteristics of the cumuli oophori, or the ability of the complexes to evolve ¹⁴C0₂ from [¹⁴ C] glucose. When oocyte-cumulus cell complexes were incubated in medium containing both dbcAMP, which blocked oocyte spontaneous maturation, and sulfated GAGs, which blocked dbcAMP-stimulated cumulus expansion, the resultant complexes resembled freshly isolated complexes morphologically. Although sulfated GAGs do not directly inhibit oocyte meiotic maturation, it is suggested that sulfated GAGs may play an indirect role in oocyte meiotic inhibition in vivo by preventing the cumulus oophorus from expanding in response to the FSH indigenous to the antral follicle prior to the LH surge.

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ACKNOWLEDGMENTS I thank Pat Ward, Rachel Snow, Avis Silva, and Lester Bunker for their assistance in this research. This project was supported by Grant PCM 79 10618 from the NSF. The Jackson Laboratory is fully accredited by the American Association for Accreditation of Laboratory Animal Care.