Estradiol Induces an Accumulation of Free Heparan Sulfate Glycosaminoglycan Chains in Uterine Epithelium*

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Abstract
Blastocyst implantation in the mouse uterus is triggered by an estrogen surge that induces a number of characteristic changes in biosynthetic activity of the endometrial stroma and epithelium, including a reduction in the thickness of the epithelial plasma membrane coat, immediately preceding attachment of the blastocyst. A brief exposure of the uterine luminal surface to 1% Nonidet-40 (NP-40) nonionic detergent extracted this surface coat along with membrane-associated and soluble [35S]sulfate-labeled proteoglycans specifically from the epithelium. Extraction from the underlying stroma appeared to have been prevented by the epithelial basal lamina, which was minimally affected by 1% NP-40, but was extracted by subsequent treatment with 1% NP-40 in 1 M KCl. About 70-80% of the [35S]sulfate in proteoglycans extracted from the uteri of ovariectomized mice with NP-40 was associated with heparan sulfate proteoglycans that eluted from Sepharose CL-4B in a peak at 0.55 Kd. All remaining radioactivity could be accounted for by dermatan sulfate/chondroitin sulfate proteoglycans. Specifically, in the NP-40 extract of uteri from ovariectomized mature mice and intact immature mice, but not in the culture medium or residual tissue, estradiol induced a pronounced increase in the relative amount of radioactivity in a 0.8 Kd peak, which appeared to contain only free heparan sulfate glycosaminoglycan chains. The same relative increase was seen in the NP-40 extract of uteri from intact 3.5-day pregnant mice. We conclude that estradiol induces cellular changes that result in an increased accumulation of epithelial heparan sulfate proteoglycan degradation product immediately preceding normal attachment of the blastocyst.