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The vaginal epithelium is the inner lining of the
vagina In mammals, the vagina is the elastic, muscular part of the female genital tract. In humans, it extends from the vestibule to the cervix. The outer vaginal opening is normally partly covered by a thin layer of mucosal tissue called the hymen ...
consisting of multiple layers of (
squamous 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 intercellula ...
) cells. The basal membrane provides the support for the first layer of the epithelium-the basal layer. The intermediate layers lie upon the basal layer, and the superficial layer is the outermost layer of the epithelium. Anatomists have described the epithelium as consisting of as many as 40 distinct layers. The mucus found on the epithelium is secreted by the cervix and uterus. The rugae of the epithelium create an involuted surface and result in a large surface area that covers 360 cm2. This large surface area allows the trans-epithelial absorption of some medications via the vaginal route. In the course of the reproductive cycle, the vaginal epithelium is subject to normal, cyclic changes, that are influenced by
estrogen 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 ac ...
: with increasing circulating levels of the
hormone A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...
, there is proliferation of epithelial cells along with an increase in the number of cell layers. As cells proliferate and mature, they undergo partial cornification. Although hormone induced changes occur in the other tissues and organs of the female reproductive system, the vaginal epithelium is more sensitive and its structure is an indicator of estrogen levels. Some
Langerhans cell A Langerhans cell (LC) is a tissue-resident macrophage of the skin. These cells contain organelles called Birbeck granules. They are present in all layers of the epidermis and are most prominent in the stratum spinosum. They also occur in the ...
s and
melanocyte Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea), the inner ear, vaginal epithelium, meninges, bones, and hear ...
s are also present in the epithelium. The epithelium of the
ectocervix The cervix or cervix uteri (Latin, 'neck of the uterus') is the lower part of the uterus (womb) in the human female reproductive system. The cervix is usually 2 to 3 cm long (~1 inch) and roughly cylindrical in shape, which changes during ...
is contiguous with that of the vagina, possessing the same properties and function. The vaginal epithelium is divided into layers of cells, including the basal cells, the parabasal cells, the superficial squamous flat cells, and the intermediate cells. The superficial cells exfoliate continuously, and basal cells replace the superficial cells that die and slough off from the
stratum corneum The stratum corneum (Latin for 'horny layer') is the outermost layer of the epidermis. The human stratum corneum comprises several levels of flattened corneocytes that are divided into two layers: the ''stratum disjunctum'' and ''stratum compa ...
. Under the stratus corneum is the
stratum granulosum The stratum granulosum (or granular layer) is a thin layer of cells in the epidermis lying above the stratum spinosum and below the stratum corneum ( stratum lucidum on the soles and palms).James, William; Berger, Timothy; Elston, Dirk (2005) '' ...
and
stratum spinosum The stratum spinosum (or spinous layer/prickle cell layer) is a layer of the epidermis found between the stratum granulosum and stratum basale. This layer is composed of polyhedral keratinocytes. These are joined with desmosomes. Their spiny (La ...
. The cells of the vaginal epithelium retain a usually high level of glycogen compared to other epithelial tissue in the body. The surface patterns on the cells themselves are circular and arranged in longitudinal rows. The epithelial cells of the uterus possess some of the same characteristics of the vaginal epithelium.


Structure

Vaginal epithelium forms transverse ridges or
rugae In anatomy, rugae are a series of ridges produced by folding of the wall of an organ. Most commonly rugae refers to the gastric rugae of the internal surface of the stomach. Function A purpose of the gastric rugae is to allow for expansion o ...
that are most prominent in the lower third of the vagina. This structure of the epithelium results in an increased surface area that allows for stretching. This layer of epithelium is protective, and its uppermost surface of cornified (dead) cells are unique in that they are permeable to microorganisms that are part of the vaginal flora. The lamina propria of
connective tissue Connective tissue is one of the four primary types of animal tissue, along with epithelial tissue, muscle tissue, and nervous tissue. It develops from the mesenchyme derived from the mesoderm the middle embryonic germ layer. Connective tiss ...
is under the epithelium.


Cells


Basal cells

The basal layer of the epithelium is the most mitotically active and reproduces new cells. This layer is composed of one layer of cuboidal cells lying on top of the basal membrane.


Parabasal cells

The parabasal cells include the stratum granulosum and the stratum spinosum. In these two layers, cells from the lower basal layer transition from active metabolic activity to death (apoptosis). In these mid-layers of the epithelia, the cells begin to lose their
mitochondria A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used ...
and other cell organelles. The multiple layers of parabasal cells are polyhedral in shape with prominent nuclei.


Intermediate cells

Intermediate cells make abundant glycogen and store it.
Estrogen 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 ac ...
induces the intermediate and superficial cells to fill with
glycogen Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy storage in animals, fungi, and bacteria. The polysaccharide structure represents the main storage form of glucose in the body. Glycogen functions as one of ...
. The intermediate cells contain nuclei and are larger than the parabasal cells and more flattened. Some have identified a transitional layer of cells above the intermediate layer.


Superficial cells

Estrogen 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 ac ...
induces the intermediate and superficial cells to fill with
glycogen Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy storage in animals, fungi, and bacteria. The polysaccharide structure represents the main storage form of glucose in the body. Glycogen functions as one of ...
. Several layers of superficial cells exist that consist of large, flattened cells with indistinct nuclei. The superficial cells are exfoliated continuously.


Cell junctions

The junctions between epithelial cells regulate the passage of molecules, bacteria and viruses by functioning as a physical barrier. The three types of structural adhesions between epithelial cells are: tight junctions,
adherens junction Adherens junctions (or zonula adherens, intermediate junction, or "belt desmosome") are protein complexes that occur at cell–cell junctions, cell–matrix junctions in epithelial and endothelial tissues, usually more basal than tight junctions. ...
s, and
desmosome A desmosome (; "binding body"), also known as a macula adherens (plural: maculae adherentes) (Latin for ''adhering spot''), is a cell structure specialized for cell-to-cell adhesion. A type of junctional complex, they are localized spot-like adh ...
s. "Tight junctions (
zonula occludens 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 ...
) are composed of
transmembrane protein A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequent ...
s that make contact across the intercellular space and create a seal to restrict
transmembrane proteins A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequentl ...
difusion. of molecules across the epithelial sheet. Tight junctions also have an organizing role in epithelial polarization by limiting the mobility of membrane-bound molecules between the apical and basolateral domains of the plasma membrane of each epithelial cell. Adherens junctions (zonula adherens) connect bundles of
actin filaments 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 p ...
from cell to cell to form a continuous adhesion belt, usually just below the microfilaments." Junction integrity changes as the cells move to the upper layers of the epidermis.


Mucus

The vagina itself does not contain mucous glands. Though
mucus Mucus ( ) is a slippery aqueous secretion produced by, and covering, mucous membranes. It is typically produced from cells found in mucous glands, although it may also originate from mixed glands, which contain both serous and mucous cells. It ...
is not produced by the vaginal epithelium, mucus originates from the cervix. The cervical mucus that is located inside the vagina can be used to assess fertility in ovulating women. The
Bartholin's glands The Bartholin's glands (named after Caspar Bartholin the Younger; also called Bartholin glands or greater vestibular glands) are two pea sized compound alveolar glandsManual of Obstetrics. (3rd ed.). Elsevier. pp. 1-16. . located slightly posteri ...
and
Skene's gland In female human anatomy, Skene's glands or the Skene glands ( , also known as the lesser vestibular glands, paraurethral glands) are glands located around the lower end of the urethra. The glands are surrounded by tissue that swells with blood ...
s located at the entrance of the vagina do produce mucus.


Development

The epithelium of the vagina originates from three different precursors during embryonic and
fetal development Prenatal development () includes the development of the embryo and of the fetus during a viviparous animal's gestation. Prenatal development starts with fertilization, in the germinal stage of embryonic development, and continues in fetal devel ...
. These are the vaginal squamous epithelium of the lower vagina, the columnar epithelium of the endocervix, and the squamous epithelium of the upper vagina. The distinct origins of vaginal epithelium may impact the understanding of
vaginal anomalies Vaginal anomalies are abnormal structures that are formed (or not formed) during the prenatal development of the female reproductive system and are rare congenital defects that result in an abnormal or absent vagina. When present, they are often f ...
.
Vaginal adenosis Vaginal adenosis is a benign abnormality in the vagina, commonly thought to be caused by intrauterine and neonatal exposure of diethylstilbestrol and other progestogens and nonsteroidal estrogens, however it has also been observed in otherwise h ...
is a vaginal anomaly traced to displacement of normal vaginal tissue by other reproductive tissue within the muscular layer and epithelium of the vaginal wall. This displaced tissue often contains glandular tissue and appears as a raised, red surface.


Cyclic variations

During the luteal and follicular phases of the estrous cycle the structure of the vaginal epithelium varies. The number of cell layers vary during the days of the estrous cycle: Day 10, 22 layers Days 12-14, 46 layers Day 19, 32 layers Day 24, 24 layers The glycogen levels in the cells is at its highest immediately before ovulation.


Lytic cells

Without estrogen, the vaginal epithelium is only a few layers thick. Only small round cells are seen that originate directly from the basal layer ( basal cells) or the cell layers (parabasal cells) above it. The parabasal cells, which are slightly larger than the basal cells, form a five- to ten-layer cell layer. The parabasal cells can also differentiate into
histiocyte A histiocyte is a vertebrate cell that is part of the mononuclear phagocyte system (also known as the reticuloendothelial system or lymphoreticular system). The mononuclear phagocytic system is part of the organism's immune system. The histiocyt ...
s or glandular cells. Estrogen also influences the changing ratios of nuclear constituents to cytoplasm. As a result of cell aging, cells with shrunken, seemingly foamy cell nuclei (intermediate cells) develop from the parabasal cells. These can be categorized by means of the nuclear-plasma relation into "upper" and "deep" intermediate cells. Intermediate cells make abundant glycogen and store it. The further nuclear shrinkage and formation of
mucopolysaccharides Glycosaminoglycans (GAGs) or mucopolysaccharides are long, linear polysaccharides consisting of repeating disaccharide units (i.e. two-sugar units). The repeating two-sugar unit consists of a uronic sugar and an amino sugar, except in the case o ...
are distinct characteristics of superficial cells. The mucopolysaccharides form a
keratin Keratin () is one of a family of structural fibrous proteins also known as ''scleroproteins''. Alpha-keratin (α-keratin) is a type of keratin found in vertebrates. It is the key structural material making up Scale (anatomy), scales, hair, Nail ...
-like cell scaffold. Fully keratinized cells without a nucleus are called "floes". Intermediate and superficial cells are constantly exfoliated from the epithelium. The glycogen from these cells is converted to sugars and then fermented by the bacteria of the vaginal flora to lactic acid. The cells progress through the cell cycle and then decompose (cytolysis) within a week's time. Cytolysis occurs only in the presence of glycogen-containing cells, that is, when the epithelium is degraded to the upper intermediate cells and superficial cells. In this way, the cytoplasm is dissolved, while the cell nuclei remain.


Epithelial microbiota

Low pH is necessary to control vaginal microbiota. Vaginal epithelial cells have a relatively high concentration of glycogen compared to other epithelial cells of the human body. The metabolism of this complex sugar by the lactobacillus dominated microbiome is responsible for vaginal acidity.


Function

The cellular junctions of the vaginal epithelium help prevent pathogenic microorganisms from entering the body though some are still able to penetrate this barrier. Cells of the cervix and vaginal epithelium generate a mucous barrier (glycocalyx) in which immune cells reside. In addition,
white blood cell White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...
s provide additional immunity and are able to infiltrate and move through the vaginal epithelium. The epithelium is permeable to antibodies, other immune system cells, and
macromolecule A macromolecule is a very large molecule important to biophysical processes, such as a protein or nucleic acid. It is composed of thousands of covalently bonded atoms. Many macromolecules are polymers of smaller molecules called monomers. The ...
s. The permeability of epithelium thus provides access for these immune system components to prevent the passage of invading pathogens into deeper vaginal tissue. The epithelium further provides a barrier to microbes by the synthesis of antimicrobial peptides ( beta-defensins and
cathelicidin Cathelicidin antimicrobial peptide (CAMP) is a polypeptide that is primarily stored in the lysosomes of macrophages and polymorphonuclear leukocytes (PMNs); in humans, the ''CAMP'' gene encodes the peptide precursor CAP-18 (18 kDa), which is proce ...
s) and immunoglobulins. Terminally differentiated, superficial keratinocytes extrude the contents of lamellar bodies out of the cell to form a specialized, intercellular
lipid Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids in ...
envelope that encases the cells of the epidermis and provides a physical barrier to microorganisms.


Clinical significance


Disease transmission

Sexually transmitted infections, including HIV are rarely transmitted across intact and healthy epithelium. These protective mechanisms are due to frequent exfoliation of the superficial cells, low pH, and innate and acquired immunity in the tissue. Research into the protective nature of the vaginal epithelium has been recommended as it would help in the design of
topical medication A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes ...
and microbicides.


Cancer

There are very rare malignant growths that can originate in the vaginal epithelium. Some are only known through case studies. They are more common in older women. *
Vaginal squamous-cell carcinoma Squamous-cell carcinoma of the vagina is a potentially invasive type of cancer that forms in the tissues of the vagina. Though uncommon, squamous-cell cancer of the vagina (SCCV) is the most common type of vaginal cancer. It is further subdivid ...
arises from the
squamous cell 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 intercellula ...
s of the epithelium. *
Vaginal adenocarcinoma In mammals, the vagina is the elastic, muscular part of the female genital tract. In humans, it extends from the Vulval vestibule, vestibule to the cervix. The outer vaginal opening is normally partly covered by a thin layer of mucous membrane ...
arises from secretory cells in the epithelium *
Clear cell adenocarcinoma of the vagina Clear-cell adenocarcinoma (CCA) of the vagina In mammals, the vagina is the elastic, muscular part of the female genital tract. In humans, it extends from the vestibule to the cervix. The outer vaginal opening is normally partly covered by ...
arises in response to prenatal exposure to
diethylstilbestrol Diethylstilbestrol (DES), also known as stilbestrol or stilboestrol, is a nonsteroidal estrogen medication, which is presently rarely used. In the past, it was widely used for a variety of indications, including pregnancy support for those with ...
*
Vaginal melanoma Vaginal melanoma is a rare malignancy that originates from melanocytes in the vaginal epithelium. It is also known as a melanocytic tumor or as a malignant melanoma. It is aggressive and infrequently cured. The median overall survival is 16 months. ...
arises from melanocytes in the epithelium


Inflammation

* Candida vaginitis is a fungal infection; the discharge is irritating to the vagina and the surrounding skin. *
Bacterial vaginosis Bacterial vaginosis (BV) is a disease of the vagina caused by excessive growth of bacteria. Common symptoms include increased vaginal discharge that often smells like fish. The discharge is usually white or gray in color. Burning with urinati ...
''
Gardnerella ''Gardnerella'' is a genus of Gram-variable In microbiology and bacteriology, Gram stain (Gram staining or Gram's method), is a method of staining used to classify bacterial species into two large groups: gram-positive bacteria and gram-negat ...
'' usually causes a discharge, itching, and irritation. *
Aerobic vaginitis Aerobic vaginitis (AV) is a form of vaginitis first described by Donders et al. in 2002. It is characterized by a more or less severe disruption of the lactobacillary flora, along with inflammation, atrophy, and the presence of a predominantly a ...
thinned reddish vaginal epithelium, sometimes with erosions or ulcerations and abundant yellowish discharge


Atrophy

The vaginal epithelium changes significantly when estrogen levels decrease at menopause. Atrophic vaginitis usually causes scant odorless discharge


History

The vaginal epithelium has been studied since 1910 by a number of histologists.


Research

The use of nanoparticles that can penetrate the cervical mucus (present in the vagina) and vaginal epithelium has been investigated to determine if medication can be administered in this manner to provide protection from infection of the Herpes simplex virus. Nanoparticle drug administration into and through the vaginal epithelium to treat HIV infection is also being investigated.


See also

*
Vaginal cysts Vaginal cysts are uncommon benign cysts that develop in the vaginal wall. The type of epithelial tissue lining a cyst is used to classify these growths. They can be congenital. They can present in childhood and adulthood. The most common type is ...
*
Vaginal tumors Vaginal tumors are neoplasms (tumors) found in the vagina. They can be benign or malignant. A neoplasm is an abnormal growth of tissue that usually forms a tissue mass. Vaginal neoplasms may be solid, cystic or of mixed type. Vaginal cancers ari ...


References


External links

* {{Epithelial types Human female reproductive system Women and sexuality Women's health Anatomy Gynaecology Epithelium