The development of the female reproductive system requires an elaborate process. In females, reproductive organs divide into three main groups: gonads, reproductive ducts, and external genitalia. The female reproductive system derives from four origins: mesoderm, primordial germ cells, coelomic epithelium, and mesenchyme. The uterus forms during Mullerian organogenesis accompanied by the development of the upper third of the vagina, the cervix, and both fallopian tubes. Knowledge of the embryology of the female reproductive tract provides insight into congenital pathologies that are related to these organs. The objective of this activity is to review uterine embryology and its clinical significance.
Up to the fifth and sixth week of fetal life, the genital system remains indifferent. Two pairs of genital ducts are present at this time: the mesonephric (Wolffian duct) and paramesonephric (Mullerian duct). In females, the absence of anti-Mullerian hormone (AMH) and SRY gene conditions the regression of Wolff ducts and further differentiation of Mullerian ducts. The upper third of the vagina, the cervix, both fallopian tubes, and the uterus derive from the paramesonephric ducts.[3] During the seventh week, paired paramesonephric ducts arise from focal invaginations of the coelomic epithelium that is found on the upper pole of each mesonephros, shortly after this the Mullerian ducts grow caudally and laterally to the urogenital ridges.
In the eighth week, a vertical fusion of paramesonephric ducts occurs. The fused cranial end gives origin to the left and right parts of what will ultimately become the uterus. This structure contains mesoderm that will form the endometrium and myometrium. The unfused cranial ends of the Mullerian ducts will develop into the fallopian tubes, the fimbrial portion of the fallopian tubes derives from the tip of this structure that remains open and acquires a funnel shape. The caudal end of the fused ducts will form the upper third of the vagina.[5] At this stage, a midline septum is present along these structures, and within the uterine cavity, this septum usually reabsorbs completely around 20 weeks, but it can persist and produce a septate uterus.[3] Regarding uterine ligaments, both the round ligament and the ovarian ligament develop from the gubernaculum, and undifferentiated mesenchymal tissue is attached to the ovary in the female fetus. The round ligament must attach to both the ovary and uterus for the ovary to be in place.[6] By the end of the first trimester development of the uterus and the other structures derived from the Mullerian ducts is complete.
For the first 10 weeks, the human fetus has the potential to become either female or male. The final phenotype depends on genetic information that influences differentiation in the embryonic structures. A female fetus will classically develop if there is the presence of a XX genotype. For a male fetus to develop there must be the presence of a Y chromosome that codes for SRY protein that enables testicular, epididymis, ductus deferens, ejaculatory duct, and seminal vesicles differentiation and secretion of anti- Mullerian hormone (AMH) from the Sertoli cells which will inhibit the further differentiation of paramesonephric ducts and condition their regression. In cases where this characteristic does not occur, an immature female fetus, or an intersex fetus will develop.
The primary function of the uterus is reproductive. The principal elements of uterine physiology are the endometrium and myometrium. The uterus accepts the ovum after fertilization, holds and provides nutrients and oxygen for the fetus and during birth, and it contracts to cause delivery. The uterus is a hormone-sensitive organ: differentiation, proliferation, exfoliation of the endometrium, and contraction during childbirth get regulated by the interaction between itself and the hypothalamus, pituitary gland, and ovaries.
Bilateral Müllerian ducts form during early human fetal life. In males, anti-müllerian hormone (AMH) secreted from the testes leads to the ducts' regression. In females, these ducts give rise to the Fallopian tubes and the uterus. In humans, the lower segments of the two ducts fuse to form a single uterus; in cases of uterine malformations this fusion may be disturbed. The different uterine morphologies among the mammals are due to varying degrees of fusion of the Müllerian ducts.
Congenital absence of uterus is also called as Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a disorder that mainly affects the female reproductive system. This condition causes the vagina and uterus to be underdeveloped or absent, although external genitalia are normal. Affected individuals usually do not have menstrual periods due to the absence of a uterus. Often, the first noticeable sign of MRKH syndrome is that menstruation does not begin by age 16 (primary amenorrhea). People with MRKH syndrome have a female chromosome pattern (46,XX) and normally functioning ovaries. They also have normal breast and pubic hair development. Although people with this condition are usually unable to carry a pregnancy, they may be able to have children through assisted reproduction.
When only reproductive organs are affected, the condition is classified as MRKH syndrome type 1. Some individuals with MRKH syndrome also have abnormalities in other parts of the body; in these cases, the condition is classified as MRKH syndrome type 2. In this form of the condition, the kidneys may be abnormally formed or positioned, or one kidney may fail to develop (unilateral renal agenesis). Affected individuals commonly develop skeletal abnormalities, particularly of the spinal bones (vertebrae). People with MRKH syndrome type 2 may also have hearing loss or heart defects.
The cause of MRKH syndrome is unknown. Changes in several genes that are involved in development before birth have been identified in people with MRKH syndrome. However, each has been found in only a few affected individuals, and it is unclear whether these changes cause MRKH syndrome. Researchers are working to determine how genetic changes might lead to problems with development of the female reproductive system.
The reproductive abnormalities of MRKH syndrome are due to incomplete development of the Müllerian duct. This structure in the embryo develops into the uterus, fallopian tubes, cervix, and the upper part of the vagina. The cause of the abnormal development of the Müllerian duct in affected individuals is unknown. Originally, researchers suspected that MRKH syndrome was caused by environmental factors during pregnancy, such as medication or maternal illness. However, subsequent studies have not identified an association with any specific maternal drug use, illness, or other factor. Researchers now suggest that in combination, genetic and environmental factors contribute to the development of MRKH syndrome, although the specific factors are often unknown.
It is also unclear why some affected individuals have abnormalities in parts of the body other than the reproductive system. Certain tissues and organs, such as the kidneys, develop from the same embryonic tissue as the Müllerian duct, and researchers suspect that problems during development could affect these organs as well
Most cases of MRKH syndrome occur in people with no history of the disorder in their family. Less often, MRKH syndrome is passed through generations in families. Its inheritance pattern is usually unclear because the signs and symptoms of the condition frequently vary among affected individuals in the same family. However, in some families, the condition appears to have an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means that one copy of the altered gene in each cell is typically sufficient to cause the disorder, although the gene involved is usually unknown.
The Müllerian structures are the structures found in the female fetus that eventually develop into a woman's reproductive organs. These structures were named after German physiologist Johannes Petrus Müller.
During typical fetal development, two tube-like structures called the Müllerian ducts fuse together to create the uterus, fallopian tubes and majority of the vagina. When one of these structures does not fully develop, a malformation of the uterus or vagina occurs, and this is referred to as a Müllerian anomaly. An anomaly that affects the uterus is called a uterine anomaly.
The various malformations are categorized based on the portion of the uterus or vagina that does not form properly, known as:
· Septate uterus: The external shape of the uterus is normal, but the cavity is divided by an extra wall of tissue called a septum, which runs down the middle of the cavity. If the septum completely divides the cavity, it is known as a septate uterus; if it partially divides the cavity, it is known as a sub-septate uterus.
· Bicornuate uterus: The external shape of the uterus is abnormal with a large indentation in the fundus (the top of the uterus), which causes the upper cavity to further divide into two cavities. This is a result of the two Müllerian ducts only partially fusing together.
· Unicornuate uterus: Only half of the uterus develops, which is the result of only one Müllerian duct developing.
· Uterine didelphys: The entire uterus and cervix is duplicated (also called a didelphic uterus), which creates two uteri and two cervices. The patient still has the standard two fallopian tubes and two ovaries. This condition is the result of the two Müllerian ducts developing, but not fusing together at all.
Doctors don't completely understand the cause of Müllerian anomalies. They are considered multifactorial, meaning they are likely caused by defects in multiple genes, with some influence from factors in our environment. The reproductive organs begin to develop when the mother is about six weeks pregnant, while an early fetus is developing inside the mother's womb, or uterus.
The reproductive organs begin to develop when the two Müllerian ducts start to migrate toward each other and begin to fuse in the middle of the fetus. Typically, some of the tissue migrates upwards to form the uterus and fallopian tubes, and the remaining tissue migrates downwards to form the vagina. Any disruption in this process may result in a malformation of the uterus, vagina, or both, which leads to a Müllerian anomaly.
Oftentimes, a patient does not have any symptoms, particularly if the uterus and vagina are patent, meaning there is no obstruction to the normal flow of menstrual blood. However, if a septum (extra wall of tissue) is present and blocks menstrual flow, patients can have symptoms of abdominal pain in the absence of menstrual bleeding, at an age when we would expect a girl to be having her monthly period.
Certain uterine anomalies, including a septate uterus, can cause recurrent miscarriages, so a miscarriage may be the first indication that a problem exists with the uterus. Finally, some malformations of the uterus, including bicornuate uterus, unicornuate uterus and uterine didelphys, may not be discovered until pregnancy, when a routine ultrasound shows a malformation. These conditions can also lead to the premature delivery of a baby, in which case the early delivery may be the first sign of the uterine malformation.
A Doctor use a 3-dimensional ultrasound, magnetic resonant imaging (MRI) or both to take images of the pelvis and evaluate the size and shape of the uterus. An MRI uses magnets to produce detailed images of the body's organs and structures, while a 3-dimensional ultrasound uses sound waves to produce images of internal organs. For the ultrasound, we move a probe along the outside of the abdomen or pelvis to see the internal images. For the MRI, the patient simply needs to lay still as the machine scans the body.
In cases where the Müllerian anomaly is associated with malformations of the skeletal system or the urinary tract, sometimes doctor use X-rays and additional imaging of the kidneys to diagnose the extent of the anomaly. An X-ray uses radiation to show images of solid structures inside the body.
In many cases, the condition can be left untreated, in particular when it does not significantly affect reproduction. Müllerian anomalies that prevent menstruation or cause significant pain are usually surgically treated. Surgical intervention depends on the extent of the individual problem.
Müllerian anomalies that affect fertility such as a septated uterus (a partitioned uterus) can be corrected, thus improving chances of having a successful pregnancy. Women with a congenital reproductive anomaly who have not been able to achieve pregnancy within six months of trying should see a fertility specialist skilled in reproductive surgery. Surgery can repair the defect, eliminate discomfort during menses or sexual relations and improve fertility and pregnancy outcomes.
A retroverted uterus means your uterus is tilted or tipped backward so it curves toward your spine instead of forward toward your abdomen. Your uterus is the organ where a baby grows during pregnancy. It’s shaped like an upside- down pear and sits in your pelvis between your bladder and your rectum. Its exact position in your pelvis varies among people and can change, especially during pregnancy
To get a better idea of how a retroverted uterus lies in your pelvis, think of your uterus like the letter U. In a retroverted uterus, the curved part of the U is aimed at your low back. The opening of the U is your cervix (the opening to the uterus from the vagina). If your uterus is retroverted, your cervix is aimed toward your belly. It’s more typical for the curved part of the U to be aimed toward your belly and your cervix to be pointed toward your rectum (this is called an anteverted uterus).
A retroverted uterus is also called a tipped uterus or tilted uterus. You can be born with a retroverted uterus or it can develop later in life. Some people never know they have a retroverted uterus because they don’t have symptoms. In some cases, you will have symptoms that may require treatment by your healthcare provider. This condition rarely causes health complications and is not a cause for worry.
A retroverted uterus is fairly common. Approximately 25% of people have a uterus that tilts backward at their cervix. An anteverted uterus means your uterus tilts forward at your cervix and points toward your abdomen. This is the more common position of the uterus. In this position, your uterus is on top of your bladder. In a retroverted uterus, your uterus is usually pressing against your rectum.
Some people don’t experience any symptoms of a retroverted uterus. For those that do have symptoms, the most common are:
· Pain during menstruation.
· Pain during sexual intercourse, especially in certain positions.
· Trouble using tampons during menstruation.
· Urinary problems like urinary tract infections (UTIs) or urinary incontinence.
Some people are born with a retroverted uterus — it’s present at birth and not caused by any health conditions. In some cases, it happens later in life.
Some reasons you can develop a tilted uterus are:
· Scarring or adhesions: Scar-like tissues from prior pelvic surgeries (including cesarean deliveries), pelvic inflammatory disease (PID) or other infections can cause the tissues in your uterus to stick to other organs. This can pull your uterus backward.
· Fibroids: Uterine fibroids or other growths on your uterus can change its shape and position.
· Endometriosis: With this condition, tissues like your uterine lining form outside your uterus. These cells can attach to other organs in your pelvis and cause your uterus to become retroverted.
· Menopause: People who are in menopause will have weakened pelvic muscles due to a decrease in the hormone estrogen. The ligaments that hold your uterus can’t support it and cause it to tip backward.
· Childbirth: Once you give birth, your pelvic floor muscles and ligaments are stretched and weaken, which can cause your uterus to tilt backward.
A doctor can tell if you have a retroverted uterus by doing a pelvic exam. During this exam, the doctor can feel the location of your cervix and uterus to determine which way it tilts. Sometimes an ultrasound is used to confirm a retroverted uterus and rule out more serious causes like uterine fibroids or endometriosis.
· Treating the underlying condition: If you have an underlying cause of a retroverted uterus, treating that condition could help improve your symptoms.
· Exercises: Some healthcare providers have experience manually shifting the uterus into a forward position. If this happens, performing exercises to strengthen your pelvic muscles can help keep your uterus in that position. Ask your healthcare provider if performing exercises like Kegels can help you improve your condition. To do Kegel exercises, tighten your pelvic muscles as if you are trying to hold back urine. Hold the muscles tight for a few seconds and then release. Exercises won’t help if your retroverted uterus is caused by scarring and it may move back to its retroverted position.
· Pessary: A pessary is a small, plastic donut-shaped device that’s inserted into your vagina. It acts as a support structure, helping to hold things in place in your vagina. It can help prop your uterus up to an anteverted position. There are some risks to pessaries, like infection and inflammation, so healthcare providers may recommend it as a short-term solution.
· Surgery: Your healthcare provider can surgically reposition your uterus to a forward-facing position. This surgery is called uterine suspension or uterine repositioning. This can permanently fix a tilted uterus and provide pain relief. In severe cases, a hysterectomy (removal of your uterus entirely) can be considered.