Uterine epithelium
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The internal surface of the
uterus The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The ...
is lined by uterine
epithelial cells Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercell ...
which undergo dramatic changes during
pregnancy Pregnancy is the time during which one or more offspring develops (gestation, gestates) inside a woman, woman's uterus (womb). A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occur ...
. The role of the uterine epithelial cells is to selectively allow the blastocyst to implant at a specific time (the time of implantation). All other times of the cycle, these uterine epithelial cells are refractory to blastocyst implantation. Uterine epithelial cells have a similar structure in most species and the changes which occur in the uterine epithelial cells at the time of blastocyst implantation are also conserved among most species.


Structure

The cytoplasm of uterine epithelial cells contains typical organelles found in other cells, including a
nucleus Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to: *Atomic nucleus, the very dense central region of an atom * Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA Nucl ...
, which is located towards the bottom of the cell with one or more prominent
nucleoli The nucleolus (, plural: nucleoli ) is the largest structure in the nucleus of eukaryotic cells. It is best known as the site of ribosome biogenesis, which is the synthesis of ribosomes. The nucleolus also participates in the formation of s ...
, mitochondria,
golgi apparatus The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic cells. Part of the endomembrane system in the cytoplasm, it packages proteins into membrane-bound vesicles ...
, endoplasmic reticulum, free
ribosomes Ribosomes ( ) are macromolecular machines, found within all cells, that perform biological protein synthesis (mRNA translation). Ribosomes link amino acids together in the order specified by the codons of messenger RNA (mRNA) molecules to ...
,
lysosomes A lysosome () is a membrane-bound organelle found in many animal cells. They are spherical vesicles that contain hydrolytic enzymes that can break down many kinds of biomolecules. A lysosome has a specific composition, of both its membrane prote ...
, vesicle (biology and chemistry), vesicles and lipid droplets. Like all epithelial cells, the uterine epithelial cells lie on a basal lamina.


Apical plasma membrane

The apical plasma membrane displays compositional variations that change at the time of implantation. The apical domain is specialized for the initial interaction with the embryo as well as controlling secretory and absorptive processes including endocytosis and pinocytosis. The apical surface of the uterine epithelial cells is covered with microvilli that are under hormonal control and vary in length and number with the oestrous cycle and during pregnancy. A hormonally dependent glycocalyx is found outside the microvilli while the center of the microvilli consists of an actin filament core which is embedded into the terminal web. The terminal web is a meshwork of actin filaments, which lies immediately below the microvilli and is important in maintaining the structural integrity of the cell surface as well as acting as a barrier to movement of cellular organelles.


Lateral plasma membrane

The lateral plasma membrane domain is responsible for cell adhesion and is believed to control the paracellular transport of fluid and electrolytes, that is transport of fluid between the cells. A junctional complex characterises this domain and consists of three specialized areas; the Tight junction, zonula occludens (tight junction), Adherens junction, zonula adherens (adherens junction) and desmosome, macula adherens (desmosome). The zonula occludens and zonula adherens form a continuous belt around the cell that provides a barrier to paracellular transport and are thought to be important in cell-cell communication.Nicholson, M., Lindsay, L. A., & Murphy, C. R. (2010). Ovarian hormones control the changing expression of claudins and occludin in rat uterine epithelial cells during early pregnancy. Acta histochemica, 112(1), 42-52.


Basal plasma membrane

The basal domain is essential for adhesion between the epithelium and underlying stroma as well as possible communication between these two regions. The uterine epithelial cells produce the basal lamina on which they rest. The basal lamina is composed of two regions; the lamina lucida that is an electron lucent layer adjacent to the basal plasma membrane and the lamina densa that is a closely packed network of fibers.


Changes at implantation

There are dramatic changes in the morphology and biochemical characteristics of the uterine epithelial cells in preparation for Implantation (human embryo), blastocyst implantation. These features include a loss of apical microvilli such that the apical plasma membrane becomes flattened.SCHLAFKE, S., & ENDERS, A. C. (1975). Cellular basis of interaction between trophoblast and uterus at implantation. Biology of Reproduction, 12(1), 41-65.Enders, A. C., & Schlafke, S. (1967). A morphological analysis of the early implantation stages in the rat. American Journal of Anatomy, 120(2), 185-225. There is also a decrease in the amount of glycocalyx covering the apical surface which leads to a reduction in the negative charge of the uterine epithelial cells. Collectively, these plasma membrane changes have been termed the plasma membrane transformation. Changes in the lateral junctional complex are important in the regulation of fluid movement along the paracellular pathway, between the epithelial cells.


Tight junction changes during early pregnancy

During the early stages of pregnancy, prior to implantation, the Tight junction, tight junction complex, which is the main regulator of paracellular flow, extends 0.4 µm down the lateral plasma membrane with little cross-linking of the tight junctional strands.Murphy, C. R., Swift, J. G., Mukherjee, T. M., & Rogers, A. W. (1982). The structure of tight junctions between uterine luminal epithelial cells at different stages of pregnancy in the rat. Cell and Tissue Research, 223(2), 281-286. At this time, the tight junctions are quite 'leaky' allowing movement of fluid and solutes between the epithelial cells.Lindsay, L. A., & Murphy, C. R. (2004). Redistribution of aquaporins in uterine epithelial cells at the time of implantation in the rat. Acta histochemica, 106(4), 299-307. At the time of implantation the tight junctions extended further down the lateral plasma membrane (1 µm) and there was a significant increase in the cross-linking of the tight junctional strands. At the time of implantation the tight junctions are electrochemically 'tighter’ and prevent the movement of fluids and electrolytes between the cells. These changes were also found in ovariectomised rats treated with exogenous hormones. Animals treated with oestrogen displayed a picture of tight junctions similar to that seen on day 1 of pregnancy while rats treated with either progesterone alone or in combination with oestrogen had tight junctions with similar morphology to that seen at the time of implantation. Various components of the tight junctions regulate the selectivity of this paracellular pathway. For example, it has been shown that it is the claudin component of tight junctions regulates the charge selectivity of the tight junctions.


Fluid transport across cells

At the time of implantation in a number of species the uterine lumen closes down, which allows uterine epithelial cells to come into contact with each other and ‘fixes’ the blastocyst in place.Enders, A. C., & Nelson, D. M. (1973). Pinocytotic activity of the uterus of the rat. American Journal of Anatomy, 138(3), 277-299. Uterine closure involves mild generalised oedema and reabsorption of luminal fluid. Fluid absorption could occur through one or a combination of mechanisms; escape of uterine fluid through the cervix, which is unlikely, as this would have the potential to displace implanting blastocysts; endocytosis by pinopods, which develop at the time of attachment, or by transcellular means. This is influenced by the tight junction molecules and ion/water channels in the apical plasma membrane of uterine epithelial cells. Studies have found an increase in CLDN4, claudin-4 within the tight junctions of uterine epithelial cells at the time of implantation and an increase in ENaC in the apical membrane of uterine epithelial cells. The increase in claudin-4 prevents the movement of Na+ ions between the cells, and the appearance of ENaC in the apical membrane allows movement of Na+ ions through the cell, from the lumen into the underlying stroma.Orchard, M. D., & Murphy, C. R. (2002). Alterations in tight junction molecules of uterine epithelial cells during early pregnancy in the rat. Acta histochemica, 104(2), 149-155. There is also an increase in AQP5 in the apical plasma membrane of uterine epithelial cells at time of implantation.Lindsay, L. A., & Murphy, C. R. (2006). Redistribution of aquaporins 1 and 5 in the rat uterus is dependent on progesterone: a study with light and electron microscopy. Reproduction, 131(2), 369-378. The osmotic gradient created by the reabsorption of Na+ ions leads to reabsorption of water through AQP5, AQP5 channels in the apical plasma membrane, which causes the uterine epithelial cells to come into contact with each other and the blastocyst.


References

{{Epithelial types Human pregnancy