Blastocyst implantation is a finely tuned process under hormonal control which requires significant remodelling of the luminal uterine epithelial cells (UECs). This includes a reorganisation of the cytoskeleton and is collectively referred to as the plasma membrane transformation. The keratin cytoskeleton is increasingly being identified as having a role in maintenance of cell polarity, apoptosis signalling and vesicular trafficking. We hypothesised that individual keratins would undergo specific reorganisation in UECs under the influence of ovarian hormones.
Ovariectomised rats were treated with estrogen or progesterone, either separately or in combination. Immunofluorescence and Western blotting revealed the unique localisation and changes in abundance of K18 and 19 filaments in each condition.
Immunofluorescence and Western blotting studies on uteri from ovariectomised rats indicated that the simple keratins are influenced differently by estrogen and progesterone. Keratin 18 expression is increased at the time of fertilisation in normal pregnancy as well as when ovariectomised rats are treated with estrogen and progesterone in combination. K19 expression was most abundant in the estrogen treated rats and notably reduced in all other conditions. Interestingly, K19 abundance is reduced at the time of receptivity in normal pregnancy.
This study has identified that simple epithelial keratins of uterine epithelial cells are under hormonal control, and that specific keratins are influenced by different hormones. An increase in K18 abundance associated with the hormonal conditions required for uterine receptivity is correlated with that seen at the time of implantation in normal pregnancy. Due to its known interaction and potential modulation of the actin and microtubule cytoskeleton, the K18 network may be an important component of the cellular transformation required for uterine receptivity. These results support the hypothesis that there are specific functions associated with individual keratins in the uterine epithelial cells and that they are under ovarian hormonal control.