3 years ago

The endometrial polarity paradox: differential regulation of polarity within secretory phase human endometrium.

Salamonsen, Whitby, Evans
A major cause of infertility in normal and assisted reproduction cycles is failure of the endometrium to undergo appropriate changes during the secretory phase of the menstrual cycle as it acquires receptivity for an implanting blastocyst. Current dogma states that loss of epithelial polarity in the luminal epithelial cells, the point of first contact between maternal endometrium and blastocyst, may facilitate embryo implantation. Loss of polarity is likely an important change during the secretory phase to overcome mutual repulsion between otherwise polarised epithelial surfaces. While the 'plasma membrane transformation' describes morphological/molecular alterations associated with loss of polarity, direct measures of polarity have not been investigated. Transepithelial resistance, a proxy measure of polarity, was down-regulated in endometrial epithelial (ECC-1) cells by combined estrogen/progestin, mimicking the hormonal milieu of the secretory phase. Examination of defined polarity markers within human endometrium throughout the menstrual cycle, identified down-regulation of atypical-PKC, Stardust, Crumbs and Scribble within the luminal-epithelial layer, with up-regulation of Scribble within the stromal compartment as the menstrual cycle progressed from estrogen-dominated proliferative to progesterone-dominated secretory phase. Epithelial (ECC-1) Scribble expression was down-regulated in vitro by combined estrogen/progestin and estrogen/progestin/hCG treatment, while knockdown of Scribble in these cells enhanced 'embryo' (trophectodermal spheroid) adhesion. In contrast, Scribble was up-regulated within decidualized primary human endometrial stromal cells, with decidualization down-regulated upon Scribble knockdown. These data highlight an important contribution of polarity modulation within the human endometrium likely important for receptivity. Clinical investigations examining how polarity may be modulated in the infertile endometrium may facilitate fertility.

Publisher URL: http://doi.org/10.1210/en.2016-1877

DOI: 10.1210/en.2016-1877

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