Caveolins redistribute in uterine epithelial cells during early pregnancy in the rat: An epithelial polarisation strategy?

Abstract

At the time of implantation, uterine luminal epithelial cells undergo a dramatic change in all plasma membrane domains. Changes in the basolateral plasma membrane at the time of implantation include progression from smooth to highly tortuous, as well as a loss of integrin-based focal adhesions. Another aspect of the basolateral plasma membrane that has not been studied in uterine epithelial cells are caveolae, which are omega-shaped invaginations of the plasma membrane known to be involved in endocytosis and contribute to membrane curvature. The current study investigated caveolin, a major protein of caveolae, to explore the possible roles that they play in the remodelling of the basolateral plasma membrane of uterine epithelial cells during early pregnancy in the rat. Morphological caveolae were found at the time of implantation and were significantly increased compared to day 1 of pregnancy. Caveolins 1 and 2 were found to shift to the basolateral plasma membrane of uterine epithelial cells at the time of implantation as well as when treated with progesterone alone, and in combination with oestrogen. A statistically significant increase in the amount of caveolin-1 and a decrease in caveolin-2 protein in uterine epithelial cells was observed at the time of implantation. Caveolin-1 also co-immunoprecipitated with integrin β1 on day 1 of pregnancy, which is a protein that has been reported to be found in integrin-based focal adhesions at the basolateral membrane on day 1 of pregnancy. The localisation and expression of caveolin-1 at the time of implantation is consistent with the presence and increase of morphological caveolae seen at this time. The localisation and expression of caveolins 1 and 2 in luminal uterine epithelium at the time of implantation suggest a role in trafficking proteins and the maintenance of a polarised epithelium.

Non‐invasive placentation in the marsupials Macropus eugenii (Macropodidae) and Trichosurus vulpecula (Phalangeridae) involves redistribution of uterine Desmoglein‐2

“…The additional nuclear and lateral localization suggests a dual role for Desmoglein‐2 in both cell signaling and cell adhesion during and after implantation in T. vulpecula (Bonné et al, ; Schlegel et al, ). This conclusion is supported by localization of Desmoglein‐2 to the apical plasma membrane during pregnancy in T. vulpecula , as apical binding of desmogleins can trigger intracellular signaling pathways (Schlegel et al, ) that may relate to maintenance of epithelial cell polarity (Madawala, Dowland, Poon, Lindsay, & Murphy, ). Apical localization of Desmoglein‐2 can also stabilize epithelial cells against apoptosis (Nava et al, ; Singh & Aplin, ), as demonstrated in intestinal epithelia following inflammation by consequent loss of cell‐cell adhesion (Nava et al, ).…”

Prominin-2 Prevents the Formation of Caveolae in Normal and Ovarian Hyperstimulated Pregnancy

“…The loss of focal adhesions at the time of implantation is a key component of the plasma membrane transformation. [14][15][16] The internalization of these adhesive complexes is thought to be driven by caveolae in UECs 18 and allows these cells to be removed to facilitate blastocyst penetration. 26,27 This study has examined prominin-2 in UECs and the potential involvement of this protein in the regulation of caveolae and it demonstrates for the first time that prominin-2 is present in the rat uterus, where it is restricted to the luminal and glandular epithelium.…”

“…For each sample, at least 30 images were taken at 50 000Â magnification and caveolae were counted in a single-blind study, where images selected were counted by an individual who was blinded to treatment status, as previously described by Madawala et al 18 Basal plasma membranes from each treatment group were measured using ImageJ software (version 1.6.0_20), and morphological caveolae (50-100 nm) with a neck connecting them to the basal plasma membrane were counted. Smooth, uncoated vesicles within the same size range and within 100 nm of the basal plasma membrane were also counted.…”

“…7,17 Another aspect of the plasma membrane transformation is a significant increase in the number of morphological caveolae in the basal plasma membrane at the time of implantation. 18 Caveolae are specialized plasma membrane subdomains enriched in cholesterol, sphingolipids, and scaffolding proteins. 19,20 These O-shaped invaginations of the plasma membrane are 50 to 100 nm in diameter and are known to compartmentalize and organize signaling proteins and receptors.…”

“…19,21 Since the internalization of caveolae drives focal adhesion turnover in other cell types, 22,23 caveolae are thought to be involved in the removal of focal adhesion components from the basal plasma membrane of UECs at the time of implantation. 18 These membrane changes facilitate the reduction in adhesion of the UECs to the underlying basal lamina, 24,25 such that they can be removed and the blastocyst can invade the underlying stroma. 26,27 A novel type of cholesterol-rich membrane lipid raft has recently been discovered in epithelial cells and shown to be associated with the prominin family of proteins.…”