Grammarly Rectified Around 1 in 7 couples may have difficulty conceiving and this is roughly 3, 5 million in the UK. (NHS choice.www.nhs.uk).
Various hyperproliferative conditions of the uterus have been causally associated with infertility. This includes endometriosis, adenomyosis and endometrial cancer 2, 3.In 2014, 9324 new uterine cancers were diagnosed in the UK and death from uterine cancers were 2166, around 6 deaths a day. NHSThe rate is projected to rise by 19% between 2014 and 2035. (Endometrial cancer counting for 92%, BMJ 2011; 343:d3954) making it the fourth most common cancer in a female in the UK after breast, lung and colorectal cancers. The reputation of cancer stem cells theory is on the rise nowadays, this prompted researchers to explore the involvement of cancer stem cells in the genesis of endometrial cancer. From a primary human endometrial cancer, Hubbart et al 167 identified a cell population with regenerative, differentiating, clonogenic and oncogenic potentials in vitro and in vivo.
Since 80% of cancers are initially epithelial, it is believed that cancers use transition mechanism (EMT and MET) to metastasize and MET plays a crucial role in the development of endometriosis through retrogrademenstruation of mesenchymal cells 171.Deep understanding of the endometrial regeneration will provide us with more insight into how these mechanisms when disturbed contribute to the development of endometrial disease and hindering fertility Routine regeneration During the menstrual cycle that occurs in humans, the endometrium undergoes a series of remodelling, differentiation, degeneration, and regeneration of epithelial and stromal cells. During the proliferative phase of the menstrual cycle, the endometrium increases in size from 1 to 11 mm just before ovulation (7). During the secretory phase that occurs just after ovulation, the endometrium reaches the maximum of its size and goes up to 16 mm.
towards the end of the secretory phase, the stromal cells of the endometrium will be transformed into decidual cells to receive the embryo by a mechanism called “decidualization” in preparation for implantation. In case of absence of pregnancy, the menstruation takes place. And the functional layer called functionalis eliminates with menstrual blood. This process lasts 3 to 5 days. (8) At the same time, the endometrium begins to regenerate from its remaining basal layer. This phenomenon occurs at least 400 times in a woman’s reproductive life.
Current knowledge about the mechanism of regeneration of the endometrium is still limited, however, certain hypotheses have been evoked. 1. Re-epithelialization of luminal epithelium (LE) by proliferation and migration of residual glandular epithelium (GE) and LE (12-18) .
2 Transdifferentiation of stromal cells to repopulate Epithelial Endometrium (19) .3.Mesenchymal and Epithelial stem cells: differentiated lineage of cells from stem cells (25-28) .4.
The intervention of cells derived from the bone marrow (20-24).The examination of the phenomenon of re-epithelialization of the endometrium has been examined through Electron microscopy scanning/transmission technique (12,13,16,17), it is suggested that the residual glandular remnants that have resisted on the stripped surface of the endometrium during menstruation, as well as the luminal epithelium which persisted at the isthmus and cornea of the uterus, were responsible for the proliferation of epithelial cells that cover the luminal surface to thereby reform the Luminal Epithelium (LE) (13,18).Cellular Transdifferentiation is a conversion of cells from one state to another under Mesenchymal to Epithelial Transition (MET) or Epithelial-Mesenchymal Transition (EMT). This phenomenon has been described for several decades in Embryology after discovering that reproductive system and the renal system have undergone a common development (29).It is known that adult stem cells play a crucial role in the regeneration and repair of tissues of several organs.
Because of their ability to self-renew, repair, maintain homeostasis, restore functions and produce a lineage differentiating offspring, it is believed that they intervene in endometrial regeneration mechanismThe intervention of bone marrow-derived cells in the maintenance and regeneration of the endometrium is still doubtful (36 Cervello et al)Label retention technique is widely used to identify stem cells relying on the assumption that as stem cells don’t divide frequently, they will retain label for longer compared to other types of cells which can dilute or lose label through frequent course of division