Microtubules are reorganised and fragmented for uterine receptivity

Abstract

For the development of uterine receptivity, many morphological and molecular changes occur in the apical surface of luminal uterine epithelial cells (UECs) including an increase in vesicular activity. Vesicular movements for exocytosis and endocytosis are dependent on microtubules; however, changes in microtubules in UECs during early pregnancy have received little attention. β-tubulin, one of the main component of microtubules, is distributed throughout the cytoplasm of UECs on day 1 (non-receptive) of pregnancy in the rat. On day 5.5, β-tubulin is concentrated above the nuclei and by day 6 (receptive), β-tubulin is concentrated in a band-like fashion above the nucleus. Western blot analysis of isolated UECs found two bands (50 and 34 kDa) for β-tubulin in UECs during early pregnancy. The intensity of the 34 kDa band was significantly higher on day 6 compared to day 1. The increase in the 34 kDa band may be due to higher proteolytic activity associated with microtubule polymerisation during the receptive state. Transmission electron microscopy showed fragmented microtubules at the time of receptivity in UECs. This is the first study to show that microtubules are reorganised during uterine receptivity. This re-organisation likely facilitates vesicular movement and promotes the reorganisation of the apical plasma membrane for uterine receptivity.

Uterine Luminal Epithelium as the Transient Gateway for Embryo Implantation

“…For example, the replacement of thick and continuous terminal webs by thinner and irregular actin bands correlates with the progressive loss of LE apical microvilli; the individually distinguishable filaments connecting actin meshworks correspond with the remaining apical plasma membrane protrusions [47]. LE microtubules become fragmented, aligned perpendicular to the apical plasma membrane, and associated with large number of vesicles in LE apical cytoplasm of a receptive rat uterus [48].…”

Protein structure–based gene expression signatures

“…S3). Both tissues' sGES also retain tissue-specific domain differences, such as ovarian tissue having sGES-containing glutathione transferase domains, which is a biomarker of oocyte viability and quality (26), while uterine tissue is enriching for proteins containing structural domains, such as the tubulin/FtsZ domain (27).…”

“…Particularly, one common structural characteristic of proteins is the overall structural family or "fold" of the protein and/or its individual domains. The structural fold or folds of a protein capture evolutionary relationships between proteins (and cognate) genes as well as protein modularity; therefore, they have a direct association with gene evolution and physiological function (26)(27)(28). Incorporating structural information has enhanced the Significance Gene expression signatures (GES) are used to define phenotypes, such as cell and tissue state, or the effects of perturbagens.…”

GLUT4 in Mouse Endometrial Epithelium: Roles in Embryonic Development and Implantation

“…embryo development and subsequent implantation in the uterus. In this process, LE cells have to go through sequential changes during early pregnancy, e.g., proliferation and differentiation (Aplin and Ruane, 2017), cytoskeleton remodeling (Tung et al, 1988;Kalam et al, 2018), vesicle trafficking (Li et al, 2020;Rai et al, 2021), secretion and resorption of uterine fluid contents (Azkargorta et al, 2018;Exposito et al, 2018;Matorras et al, 2020), etc., to reach into a receptive state that supports embryo implantation. All these LE changes are energy-consuming processes, which undoubtedly depend on glucose uptake and metabolism.…”