Expression of human MUC1 during early pregnancy in the human MUC1 transgenic mouse model.
Embryo implantation involves direct interaction of the blastocyst with the luminal epithelium of the receptive uterus. MUC1, a transmembrane mucin expressed at the apical surface of uterine epithelia, acts as a barrier to microbial infection and enzymatic attack. Loss of MUC1 is believed to be a prerequisite for a functionally receptive uterus across many species. Human and murine MUC1 regulation by steroid hormones displays important differences. Estrogen (E2) stimulates MUC1 expression in mice, and progesterone (P4) antagonizes E2 action in this regard. MUC1 expression is severely reduced during the receptive uterine state in mice. In contrast, human MUC1 expression is maximal at the receptive or midluteal phase, when P4 levels are high. No information is available regarding regulation of human MUC1 in vivo at the site of embryo attachment. Our aim was to better understand regulation of human MUC1 during early pregnancy in vivo. For this purpose, we used a transgenic mouse carrying full-length human MUC1 gene (Tg(MUC1)79.24Gend) as well as endogenous MUC1 as a model system. Human MUC1 was detected by real-time RT-PCR, Western blotting, and immunohistochemistry during early pregnancy. Our data indicate that human MUC1 persists at reduced (20% relative to Day 1 postcoitum) levels in receptive-phase uteri, including the site of embryo attachment. In contrast, mouse MUC1 was much more severely (>98% relative to Day 1 postcoitum) reduced in the same context. These observations are consistent with distinct regulation between the human and mouse genes. Because these genes are expressed in the same transcriptional context (i.e., mouse uterine epithelia), structural differences between human and murine genes must account for these differences in MUC1 regulation.
Dharmaraj
Neeraja
N
Department of Biological Sciences, University of Delaware, Newark, Delaware, USA.
Gendler
Sandra J
SJ
Carson
Daniel D
DD
D000818:Animals; D015153:Blotting, Western; D010064:Embryo Implantation / Q000235:genetics*; D004717:Endometrium / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018396:Mucin-1 / Q000235:genetics* / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013045:Species Specificity
D018396:Mucin-1; D012333:RNA, Messenger
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