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 Vesicle may refer to: ; In cellular biology or chemistry * Vesicle (biology and chemistry) In cell biology, a vesicle is a structure within or outside a cell, consisting of liquid or cytoplasm enclosed by a lipid bilayer. Vesicles form nat ...

s 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 In cellular biology, pinocytosis, otherwise known as fluid endocytosis and bulk-phase pinocytosis, is a mode of endocytosis in which small molecules dissolved in extracellular fluid are brought into the cell through an invagination of the cell ...

. 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 The glycocalyx, also known as the pericellular matrix, is a glycoprotein and glycolipid covering that surrounds the cell membranes of bacteria, epithelial cells, and other cells. In 1970, Martinez-Palomo discovered the cell coating in animal c ...

is found outside the microvilli while the center of the microvilli consists of an

actin filament Microfilaments, also called actin filaments, are protein filaments in the cytoplasm of eukaryotic cells that form part of the cytoskeleton. They are primarily composed of polymers of actin, but are modified by and interact with numerous other pro ...

core which is embedded into the

terminal web The terminal web is a filamentous structure found at the apical surface of epithelial cells that possess microvilli. It is composed primarily of actin filaments stabilized by spectrin, which also anchors the terminal web to the apical cell membra ...

. 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 Paracellular transport refers to the transfer of substances across an epithelium by passing through the intercellular space ''between'' the cells. It is in contrast to transcellular transport, where the substances travel ''through'' the cell, pass ...

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 zonula occludens (tight junction), zonula adherens (adherens junction) and macula adherens (desmosome). The zonula occludens and zonula adherens form a continuous belt around the cell that provides a barrier to

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 The lamina lucida is a component of the basement membrane which is found between the epithelium and underlying connective tissue (e.g., epidermis and dermis of the skin). It is a roughly 40 nanometre wide electron-lucent zone between the plasma ...

that is an electron lucent layer adjacent to the basal plasma membrane and the

lamina densa The lamina densa is a component of the basement membrane zone between the epidermis and dermis of the skin, and is an electron-dense zone between the lamina lucida and dermis, synthesized by the basal cells of the epidermis, and composed of (1) ...

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 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

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 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 Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...

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 Claudins are a family of proteins which, along with occludin, are the most important components of the tight junctions ( zonulae occludentes). Tight junctions establish the paracellular barrier that controls the flow of molecules in the interce ...

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 Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels tight, the area ma ...

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 The blastocyst is a structure formed in the early embryonic development of mammals. It possesses an inner cell mass (ICM) also known as the ''embryoblast'' which subsequently forms the embryo, and an outer layer of trophoblast cells called the t ...

; endocytosis by pinopods, which develop at the time of attachment, or by

transcellular Transcellular transport involves the transportation of solutes by a cell ''through'' a cell. Transcellular transport can occur in three different ways active transport, passive transport, and transcytosis. Active Transport Main article: Active ...

means. This is influenced by the

tight junction Tight junctions, also known as occluding junctions or ''zonulae occludentes'' (singular, ''zonula occludens''), are multiprotein junctional complexes whose canonical function is to prevent leakage of solutes and water and seals between the epith ...

molecules and ion/water channels in the apical plasma membrane of uterine epithelial cells. Studies have found an increase in claudin-4 within the

tight junctions Tight junctions, also known as occluding junctions or ''zonulae occludentes'' (singular, ''zonula occludens''), are multiprotein junctional complexes whose canonical function is to prevent leakage of solutes and water and seals between the epith ...

of uterine epithelial cells at the time of implantation and an increase in

ENaC The epithelial sodium channel (ENaC), (also known as amiloride-sensitive sodium channel) is a membrane-bound ion channel that is selectively permeable to sodium ions (). It is assembled as a heterotrimer composed of three homologous subunits α ...

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 Osmosis (, ) is the spontaneous net movement or diffusion of solvent molecules through a selectively-permeable membrane from a region of high water potential (region of lower solute concentration) to a region of low water potential (region of ...

created by the reabsorption of Na+ ions leads to reabsorption of water through 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