Female Reproductive Tract

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

Abstract
In order for the pre-implantation 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 non-adhesive 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 CR. Hum Reprod 2000; 15:2451-2454)). Previous research has led to the hypothesis that loss of the non-adhesive 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. 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 non-receptive luminal uterine surface which prevents cell adhesion and that its removal during uterodome formation facilitates adhesion of the trophoblast.

Key words: Female Reproductive Tract • Implantation • Trophoblast • Uterus