Cervical mucus plug

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A cervical mucus plug (operculum) is a plug that fills and seals the cervical canal during pregnancy. It is formed by a small amount of cervical mucus that condenses to form a cervical mucus plug during pregnancy. [1]

Contents

The cervical mucus plug (CMP) acts as a protective barrier by deterring the passage of bacteria into the uterus, and contains a variety of antimicrobial agents, including immunoglobulins, and similar antimicrobial peptides to those found in nasal mucus.The CMP inhibits the migration of vaginal bacteria towards the uterus, protecting against opportunistic infections that can lead to pelvic inflammatory disease and the onset of preterm labor. Ensuring the presence and proper function of the CMP is essential in reducing severe infections and promoting overall reproductive health. [1]

During pregnancy, the mucus has viscoelastic properties and can be described as cloudy, clear, thick, salty and sticky. It holds innate and adaptive immunity properties allowing for protection of the cervical epithelium during pregnancy. Toward the end of the pregnancy, when the cervix thins, some blood is released into the cervix which causes the mucus to become bloody. As the pregnancy progresses into labor, the cervix begins to dilate and the mucus plug is discharged. The plug may come out as a plug, a lump, or simply as increased vaginal discharge over several days. Loss of the mucus plug does not necessarily mean that delivery or labor is imminent. [2]

Having intercourse or a vaginal examination can also disturb the mucus plug and cause a pregnant individuals to see some blood-tinged discharge, even when labor does not begin over the next few days. [1]

A cervical mucus plug can allow for identification of an individual's ovulation cycle and serve as fertility indicator. The cervical mucus plug proteome changes throughout an individual's menstrual cycle and allows for identification of specific proteins that may represent different stages of ovulation. [3]

Some proteins found within the cervical mucus of patients with endometriosis could serve as potential biomarkers for the disease. [3]

Components

Cervicovaginal mucus is composed of water, gel-forming-mucins (GFMS), and vaginal flora. GMFS are a combination of proteins and other molecules that are responsible for the viscoelastic properties of the mucus. [1] Cervical mucus is formed by secretory cells within the cervical crypts. [3]

Mucus glycoproteins (mucins) provide structural framework for a CMP, they determine the elasticity and fluid mechanics of a cervical mucus plug. [2]

Function

Mucus within the genital tract serves numerous biological functions such as maintaining mucosa moisture, providing lubrication during intercourse, supporting fertility, and restricting ascending sperm cells during ovulation. [1]

The mucus glycoproteins (mucins) mentioned previously have five major components. The first is their ligand function for lectins, adhesion molecules, growth factors, cytokines, and chemokines. Second, they are responsible for binding water in CMPs and determines its hydration state. Third, mucins exclude lager molecules and bacteria which prevents bacterial infections in the lower genital tract. Mucins inhibit diffusion of these large molecules, while smaller molecules can diffuse through the CMP more freely. Fourth, mucins are responsible for the retention of positively charged molecules, while negative charged molecules are repelled and pass through the CMP. This is due to the negatively charged oligosaccharide chains in the mucins, which promote retention of the positively charged molecules. Lastly, mucins inhibit viral replication of poxvirus and human immunodeficiency virus (HIV) in vitro. In addition, mucins can also create a communication between the CMP and cervical epithelium. [2]

Antimicrobial properties

The cervical mucus plug (CMP) has a viscoelastic structure which is a gel like. The CMP occupies the cervical canal during pregnancy. It displays potent antimicrobial properties against bacteria such as Staphylococcus saprophyticus, S. aureus, Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecium, Streptococcus pyogenes, and S. agalactiae.

Naturally occurring Lactobacillus species within the cervicovaginal mucus flora offer protection from harmful microbes by producing lactic acid, bacteriocins, and other molecules that lower the pH level and increase mucus viscosity. These changes reduce the adherence of harmful bacteria to the epithelial tissue. [5]

Menstrual cycle

Throughout the menstrual cycle, the cervical mucus undergoes distinct changes. During the follicular phase, increasing levels of estrogen result in greater mucus volume and gradual reduction in thickness. Ovulation triggers significant surges in mucus levels due to high expression of MUC5B which creates a watery consistency that aids sperm mobility into the reproductive tract. In the luteal phase, progesterone leads to a decrease in MUC5B expression, resulting in the thickening of cervical mucus. Immune factors and antimicrobial peptides vary a different stages of the menstrual cycle. [6]

Pregnancy

Healthy pregnancy results in a dense CMP which protects the uterine cavity from infection. [1] Elevated progesterone plasma levels induce cervical mucus to form a more viscous plug called the CMP. [7]

One of the most common causes of preterm birth is inflammation induced by the changes in vaginal bacterial flora. [8] Lactobacillus plays an important role in maintaining the vaginal PH by producing lactic acids that protects against infections. Lactobacillus bacteria reduction in the vaginal bacterial flora leads other anaerobic bacteria to grow more easily. It also lead to increased cervical mucus IL-8 and increased preterm birth. [8] Dysbiosis occurs when the presence of naturally occurring bacteria such as lactobacilli declines resulting in an increase of harmful bacteria within the vagina. These changes result a CMP that is thin and porous which can leave the uterine compartment susceptible to infection. [1]

Infections of the placenta and amniotic fluid by bacteria found in the vagina have been closely correlated to preterm labor. [7] The CMP of pregnant women is in direct contact with the supracervical region of the chorioamniotic membranes which contain amniotic fluid. This allows direct protection of the fetus. [7]

Complications

Impairment of a CMP may be caused by cervical effacement, resulting in loss of the CMP. [2] The CMP's most important task is to protect reproductive organs against infection by microorganisms coming from the vagina. It does so with a variety of polypeptides that have activity against microorganisms and immunoglobulins. [9] Without protection by the CMP, infection can occur leading to a number of complications. [10]

Preterm birth

Cervical mucus plug in women at high risk Vs low risk of preterm birth. Pone.0069528.g006.png
Cervical mucus plug in women at high risk Vs low risk of preterm birth.

A common complication in pregnancy is preterm birth, as mentioned before. Preterm birth is birth prior to 37 weeks of gestation. In individuals with a higher risk for preterm birth, the CMP is found to be more translucent, extensible, and permeable compared to those at low risk for preterm birth. These individuals also may display shorter cervix which can result in increased risk of intra-amniotic infection. [7] The permeability of the CMP is the most important factor as it can allow for a higher risk for the entrance of foreign particles that are harmful. It seems that those at a higher risk for preterm birth develop a less thick and impermeable CMP during the pregnancy, which in turn allows for the entrance of more foreign particles such as bacteria, which is a known cause of preterm birth.

HPV infections

Dysbiosis in the cervicovaginal microbiota has been closely associated with increased HPV infections. Human papillomaviruses are a type of double-stranded DNA viruses categorized within the Papillomaviridae family. HPV infections are primarily transmitted through sexual contact. A healthy vaginal microbiota plays a crucial role in preventing various urogenital infections including sexually transmitted diseases. However, HPV infection occurs when it inhibits the production of cytokines, leading to changes in the microbial interactions within the cervical microenvironment. [11] [12] Lactobacillus bacteria plays an important role in maintaining the PH of the vagina by producing lactic acid. The lactate generated by lactobacilli elevates the thickness of cervical mucus, creating a barrier that entangles viral particles and hinders papillomavirus from reaching basal keratinocytes, which plays an important role in protection. When lactobacillus bacterias decline, the vaginal microbiota is dominated by non lactobacillus species. This increases the risk of HPV infections. [11]

Related Research Articles

<span class="mw-page-title-main">Bacterial vaginosis</span> Excessive growth of bacteria in the vagina

Bacterial vaginosis (BV) is an infection 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 urination may occur. Itching is uncommon. Occasionally, there may be no symptoms. Having BV approximately doubles the risk of infection by a number of sexually transmitted infections, including HIV/AIDS. It also increases the risk of early delivery among pregnant women.

<span class="mw-page-title-main">Cervix</span> Lower part of the uterus in the female reproductive system

The cervix or cervix uteri is a dynamic fibromuscular organ of the female reproductive system that connects the vagina with the uterine cavity. The human cervix has been documented anatomically since at least the time of Hippocrates, over 2,000 years ago[citation needed]. The cervix is approximately 4 cm long with a diameter of approximately 3 cm and tends to be described as a cylindrical shape, although the front and back walls of the cervix are contiguous. The size of the cervix changes throughout a women's life cycle. For example, during their fertile years of the reproductive cycle, females tend to have a larger cervix vis á vis postmenopausal females; likewise, females who have produced offspring have a larger sized cervix than females who have not produced offspring.

Cervical dilation is the opening of the cervix, the entrance to the uterus, during childbirth, miscarriage, induced abortion, or gynecological surgery. Cervical dilation may occur naturally, or may be induced surgically or medically.

Bloody show or show is the passage of a small amount of blood or blood-tinged mucus through the vagina near the end of pregnancy. It is caused by thinning and dilation of the cervix, leading to detachment of the cervical mucus plug that seals the cervix during pregnancy and tearing of small cervical blood vessels, and is one of the signs that labor may be imminent. The bloody show may be expelled from the vagina in pieces or altogether and often appears as a jelly-like piece of mucus stained with blood. Although the bloody show may be alarming at first, it is not a concern of patient health after 37 weeks gestation.

<span class="mw-page-title-main">Prelabor rupture of membranes</span> Medical condition

Prelabor rupture of membranes (PROM), previously known as premature rupture of membranes, is breakage of the amniotic sac before the onset of labor. Women usually experience a painless gush or a steady leakage of fluid from the vagina. Complications in the baby may include premature birth, cord compression, and infection. Complications in the mother may include placental abruption and postpartum endometritis.

<span class="mw-page-title-main">Cervical effacement</span>

Cervical effacement or cervical ripening refers to the thinning and shortening of the cervix. This process occurs during labor to prepare the cervix for dilation to allow the fetus to pass through the vagina. While this a normal, physiological process that occurs at the later end of pregnancy, it can also be induced through medications and procedures.

<span class="mw-page-title-main">Cervical cerclage</span> Obstetrics medical procedure

Cervical cerclage, also known as a cervical stitch, is a treatment for cervical weakness, when the cervix starts to shorten and open too early during a pregnancy causing either a late miscarriage or preterm birth. In women with a prior spontaneous preterm birth and who are pregnant with one baby, and have shortening of the cervical length less than 25 mm, a cerclage prevents a preterm birth and reduces death and illness in the baby.

<span class="mw-page-title-main">Cervical intraepithelial neoplasia</span> Medical condition

Cervical intraepithelial neoplasia (CIN), also known as cervical dysplasia, is the abnormal growth of cells on the surface of the cervix that could potentially lead to cervical cancer. More specifically, CIN refers to the potentially precancerous transformation of cells of the cervix.

<span class="mw-page-title-main">Salpingitis</span> Medical condition

Salpingitis is an infection causing inflammation in the fallopian tubes. It is often included in the umbrella term of pelvic inflammatory disease (PID), along with endometritis, oophoritis, myometritis, parametritis, and peritonitis.

<span class="mw-page-title-main">Vaginal discharge</span> Medical condition

Vaginal discharge is a mixture of liquid, cells, and bacteria that lubricate and protect the vagina. This mixture is constantly produced by the cells of the vagina and cervix, and it exits the body through the vaginal opening. The composition, amount, and quality of discharge varies between individuals and can vary throughout the menstrual cycle and throughout the stages of sexual and reproductive development. Normal vaginal discharge may have a thin, watery consistency or a thick, sticky consistency, and it may be clear or white in color. Normal vaginal discharge may be large in volume but typically does not have a strong odor, nor is it typically associated with itching or pain. While most discharge is considered physiologic or represents normal functioning of the body, some changes in discharge can reflect infection or other pathological processes. Infections that may cause changes in vaginal discharge include vaginal yeast infections, bacterial vaginosis, and sexually transmitted infections. The characteristics of abnormal vaginal discharge vary depending on the cause, but common features include a change in color, a foul odor, and associated symptoms such as itching, burning, pelvic pain, or pain during sexual intercourse.

<span class="mw-page-title-main">Vaginal flora</span> Microorganisms present in the vagina

Vaginal flora, vaginal microbiota or vaginal microbiome are the microorganisms that colonize the vagina. They were discovered by the German gynecologist Albert Döderlein in 1892 and are part of the overall human flora. The amount and type of bacteria present have significant implications for an individual's overall health. The primary colonizing bacteria of a healthy individual are of the genus Lactobacillus, such as L. crispatus, and the lactic acid they produce is thought to protect against infection by pathogenic species.

<span class="mw-page-title-main">Vaginal delivery</span> Delivery through the vagina

A vaginal delivery is the birth of offspring in mammals through the vagina. It is the most common method of childbirth worldwide. It is considered the preferred method of delivery, with lower morbidity and mortality than caesarean sections (C-sections).

Prevotella is a genus of Gram-negative bacteria.

The vaginal flora in pregnancy, or vaginal microbiota in pregnancy, is different from the vaginal flora before sexual maturity, during reproductive years, and after menopause. A description of the vaginal flora of pregnant women who are immunocompromised is not covered in this article. The composition of the vaginal flora significantly differs in pregnancy. Bacteria or viruses that are infectious most often have no symptoms.

The Human Microbiome Project (HMP), completed in 2012, laid the foundation for further investigation into the role the microbiome plays in overall health and disease. One area of particular interest is the role which delivery mode plays in the development of the infant/neonate microbiome and what potential implications this may have long term. It has been found that infants born via vaginal delivery have microbiomes closely mirroring that of the mother's vaginal microbiome, whereas those born via cesarean section tend to resemble that of the mother's skin. One notable study from 2010 illustrated an abundance of Lactobacillus and other typical vaginal genera in stool samples of infants born via vaginal delivery and an abundance of Staphylococcus and Corynebacterium, commonly found on the skin surfaces, in stool samples of infants born via cesarean section. From these discoveries came the concept of vaginal seeding, also known as microbirthing, which is a procedure whereby vaginal fluids are applied to a new-born child delivered by caesarean section. The idea of vaginal seeding was explored in 2015 after Maria Gloria Dominguez-Bello discovered that birth by caesarean section significantly altered the newborn child's microbiome compared to that of natural birth. The purpose of the technique is to recreate the natural transfer of bacteria that the baby gets during a vaginal birth. It involves placing swabs in the mother's vagina, and then wiping them onto the baby's face, mouth, eyes and skin. Due to the long-drawn nature of studying the impact of vaginal seeding, there are a limited number of studies available that support or refute its use. The evidence suggests that applying microbes from the mother's vaginal canal to the baby after cesarean section may aid in the partial restoration of the infant's natural gut microbiome with an increased likelihood of pathogenic infection to the child via vertical transmission.

<span class="mw-page-title-main">Uterine microbiome</span>

The uterine microbiome is the commensal, nonpathogenic, bacteria, viruses, yeasts/fungi present in a healthy uterus, amniotic fluid and endometrium and the specific environment which they inhabit. It has been only recently confirmed that the uterus and its tissues are not sterile. Due to improved 16S rRNA gene sequencing techniques, detection of bacteria that are present in low numbers is possible. Using this procedure that allows the detection of bacteria that cannot be cultured outside the body, studies of microbiota present in the uterus are expected to increase.

<span class="mw-page-title-main">Vaginal epithelium</span> Inner lining of the vagina

The vaginal epithelium is the inner lining of the vagina consisting of multiple layers of (squamous) 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 of cells. 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.

<span class="mw-page-title-main">Lactobacillus vaccine</span> Vaccine using an inactivated strain of Lactobacillus

Lactobacillus vaccines are used in the therapy and prophylaxis of non-specific bacterial vaginitis and trichomoniasis. The vaccines consist of specific inactivated strains of Lactobacilli, called "aberrant" strains in the relevant literature dating from the 1980s. These strains were isolated from the vaginal secretions of patients with acute colpitis. The lactobacilli in question are polymorphic, often shortened or coccoid in shape and do not produce an acidic, anti-pathogenic vaginal environment. A colonization with aberrant lactobacilli has been associated with an increased susceptibility to vaginal infections and a high rate of relapse following antimicrobial treatment. Intramuscular administration of inactivated aberrant lactobacilli provokes a humoral immune response. The production of specific antibodies both in serum and in the vaginal secretion has been demonstrated. As a result of the immune stimulation, the abnormal lactobacilli are inhibited, the population of normal, rod-shaped lactobacilli can grow and exert its defense functions against pathogenic microorganisms.

<span class="mw-page-title-main">Cervical drug delivery</span> Drug delivery methodology

Cervical drug delivery is a route of carrying drugs into the body through the vagina and cervix. This is a form of localized drug delivery that prevents the drugs from impacting unintended areas of the body, which can lower side effects of toxic drugs such as chemotherapeutics. Cervical drug delivery has specific applications for a variety of female health issues: treatment of cervical cancer, pregnancy prevention, STD prevention, and STD treatment. 

References

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  3. 1 2 3 Fernandez-Hermida Y, Grande G, Menarguez M, Astorri AL, Azagra R (2018). "Proteomic Markers in Cervical Mucus". Protein and Peptide Letters. 25 (5): 463–471. doi:10.2174/0929866525666180418122705. PMID   29667544. S2CID   4956453.
  4. ↑ Hansen LK, Becher N, Bastholm S, Glavind J, Ramsing M, Kim CJ, et al. (January 2014). "The cervical mucus plug inhibits, but does not block, the passage of ascending bacteria from the vagina during pregnancy". Acta Obstetricia et Gynecologica Scandinavica. 93 (1): 102–108. doi:10.1111/aogs.12296. PMC   5987199 . PMID   24266587.
  5. ↑ Frąszczak K, Barczyński B, Kondracka A (October 2022). "Does Lactobacillus Exert a Protective Effect on the Development of Cervical and Endometrial Cancer in Women?". Cancers. 14 (19): 4909. doi: 10.3390/cancers14194909 . PMC   9564280 . PMID   36230832.
  6. ↑ Dong M, Dong Y, Bai J, Li H, Ma X, Li B, et al. (2023). "Interactions between microbiota and cervical epithelial, immune, and mucus barrier". Frontiers in Cellular and Infection Microbiology. 13: 1124591. doi: 10.3389/fcimb.2023.1124591 . PMC   9998931 . PMID   36909729.
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  9. ↑ Hein M, Petersen AC, Helmig RB, Uldbjerg N, Reinholdt J (August 2005). "Immunoglobulin levels and phagocytes in the cervical mucus plug at term of pregnancy". Acta Obstetricia et Gynecologica Scandinavica. 84 (8): 734–742. doi: 10.1111/j.0001-6349.2005.00525.x . PMID   16026397. S2CID   20962823.
  10. ↑ Critchfield AS, Yao G, Jaishankar A, Friedlander RS, Lieleg O, Doyle PS, et al. (2013-08-01). "Cervical mucus properties stratify risk for preterm birth". PLOS ONE. 8 (8): e69528. Bibcode:2013PLoSO...869528C. doi: 10.1371/journal.pone.0069528 . PMC   3731331 . PMID   23936335.
  11. 1 2 Santella, Biagio; Schettino, Maria T.; Franci, Gianluigi; De Franciscis, Pasquale; Colacurci, Nicola; Schiattarella, Antonio; Galdiero, Massimiliano (2022). "Microbiota and HPV: The role of viral infection on vaginal microbiota". Journal of Medical Virology. 94 (9): 4478–4484. doi:10.1002/jmv.27837. ISSN   0146-6615. PMC   9544303 . PMID   35527233.
  12. ↑ Norenhag, J; Du, J; Olovsson, M; Verstraelen, H; Engstrand, L; Brusselaers, N (2019). "The vaginal microbiota, human papillomavirus and cervical dysplasia: a systematic review and network meta-analysis". BJOG: An International Journal of Obstetrics & Gynaecology. 127 (2): 171–180. doi:10.1111/1471-0528.15854. ISSN   1470-0328. PMID   31237400. S2CID   195357045.
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