Pinopodes, Leukemia Inhibitory Factor, Integrin-β3, and Mucin-1 Expression in the Peri-implantation Endometrium of Women with Unexplained Recurrent Pregnancy Loss

Mucin-1 expression is lower in peri-implantation endometrium of women with recurrent pregnancy loss than in controls, but pinopode morphology and coverage, and leukemia inhibitory factor and integrin-b3 expression are similar.

Bufang Xu, Ph.D., Xiaoxi Sun, Ph.D., Lu Li, M.S., Ling Wu, M.S., Aijun Zhang, Ph.D., Yun Feng, M.D., Ph.D.

Volume 98, Issue 2 , Pages 389-395, August 2012


To compare pinopode morphology and coverage, and expression of leukemia inhibitory factor (LIF), integrin-β3, and mucin-1 (MUC1) in the peri-implantation endometrium of women with unexplained recurrent pregnancy loss (RPL) versus normal fertile women.

Exploratory clinical study.

University-affiliated assisted reproductive center.

Women undergoing assisted reproduction at centers of reproductive medicine in two university teaching hospitals.

Endometrial biopsy samples were obtained from women with RPL (test group, n = 30) and normal fertile women (control group, n = 26) 7 days after the day of luteinizing hormone peak. Pinopode morphology and coverage were assessed by use of scanning electron microscopy. Expression of LIF, integrin β3, and MUC1 were evaluated by immunohistochemical staining.

Main Outcome Measure(s):
Pinopode morphology and coverage, and the expression of LIF, integrin-β3, and MUC1 in both groups.

Pinopode morphology and coverage, and the expression of LIF and integrin-β3 showed no statistically significant differences between the two groups. The expression of MUC1 was statistically significantly reduced in the glandular epithelial cells and endometrial lumen of the RPL group compared with controls.

The morphology and the coverage of pinopodes and expression of LIF and integrin-β3 did not change, but MUC1 expression was statistically significantly reduced in women with RPL compared with normal women.

  • Bruce A. Lessey

    The study, while interesting, requires some clarification, since the antibodies used for these studies are not available in the US. The catalog numbers listed for beta 3 and LIF, respectively (BA0906 and BA1239) appear to be typographical errors according to the source (Boster Biological Technology, LTD), since all their polyclonals begin with “PA”, not “BA”. PA1239 is listed in their catalog as an antibody against GFAP, not LIF. The one antibody against LIF that is listed by Boster is recommended only for western blot (PA1562). Further, polyclonals against integrins are notoriously difficult to use in formalin fixed tissues and therefore the results may not be valid (see Lessey and Castelbaum Hum Reprod 13:3578).When they do work, they require antigen retrieval. Positive controls were reportedly used, but the actual types of tissues used for LIF and beta 3 are not listed nor results shown. Ideally, tissues negative and positive for the antigens in question should be employed. Finally, two studies have found poor association between pinopodes and endometrial window of implantation (Usadi et al., 2003, Fert Stert 79:970-4; Quinn and Casper, 2009 Human Reprod Update 15:229-236). This highly subjective measure (which is the only finding that was different between groups) is even more subjective when one tries to estimate whether the static images on SEM represent developing or regressing structures. Given the difficulties in authenticating what antibodies were actually used in these studies, the results should be, for the moment, taken with a very large grain of salt.

  • mmeseguer

    Congratulations for your work.
    I did my PhD work on MUC1 expression on epithelial cells, and an extensive work in an in vitro model analyzing the effect of the embryo on the expression on MUC1 on the implantation site. We found an exciting down regulation of this mucin by the embryo only in the place where the embryo implanted. I missed the citation of this paper in the discussion, Meseguer et al. 2001 Biology of Reproduction.

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