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This Article Full Text Full Text (PDF) [Supplemental Figure] All Versions of this Article: 78/1/134    most recent biolreprod.106.058347v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Gipson, I. K Articles by Gemzell, K. Search for Related Content PubMed PubMed Citation Articles by Gipson, I. K Articles by Gemzell, K. Agricola Articles by Gipson, I. K Articles by Gemzell, K.

MUC16 Is Lost from the Uterodome (Pinopode) Surface of the Receptive Human Endometrium: In Vitro Evidence That MUC16 Is a Barrier to Trophoblast Adherence¹

Schepens Eye Research Institute,⁴ Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114 Departments of Clinical Science, Intervention, and Technology⁵ and Woman and Child Health,⁶ Division of Obstetrics and Gynecology, Karolinska Institutet, Stockholm 171 77 Sweden

ABSTRACT

In order for the preimplantation embryo to implant into the uterus, the trophoblast cells must initially adhere to the uterine epithelial surface. In preparation, the luminal secretory cells of the epithelium lose their nonadhesive character and their surface microvilli and bulge into the lumen, forming uterodomes (pinopodes; uterodome is used instead of pinopode, since in humans the surface membrane exocytoses rather than endocytoses (Murphy, Hum Reprod 2000; 15:2451–2454). Previous research has led to the hypothesis that loss of the nonadhesive membrane-spanning mucin MUC1 from the uterodome surface allows trophoblast adherence. Immunofluorescence microscopic assay of luminal epithelia on human uterine biopsies taken from LH+0 to LH+13 show that another membrane-spanning mucin, MUC16, was lost from uterodome surfaces in all samples taken during the receptive phase, LH+6 to LH+8 (n = 12), and that MUC1 was present on uterodomes in 4 of 12 samples and on all ciliated cells of the epithelium in the receptive phase. Short interfering RNA (siRNA) knockdown of MUC16 in a uterine epithelial cell line ECC-1 that, like uterine epithelium, expresses MUC16 and MUC1 allowed increased adherence of cells of a trophoblast cell line. In parallel experiments, siRNA knockdown of MUC1 did not affect trophoblast cell adherence. These data indicate that MUC16 is a membrane component of the nonreceptive luminal uterine surface, which prevents cell adhesion, and that its removal during uterodome formation facilitates adhesion of the trophoblast.

female reproductive tract, implantation, trophoblast, uterus

³ These authors contributed equally to this work.

¹Supported by National Institutes of Health/National Eye Institute (NIH/NEI) R01 EY03306 to I.K.G., and NIH/NEI F32 EY016937 to T.B.

³These authors contributed equally to this work.

Correspondence: ²Ilene K. Gipson, Schepens Eye Research Institute, 20 Staniford St., Boston, MA 02114. FAX: 617 912 0126; e-mail: Ilene.Gipson{at}schepens.harvard.edu