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Development of the reproductive system
Sexual differentiation and determination of the organs of the reproductive system is guided by the presence of a Y or X chromosome. In other words, upon fertilization, we are genetically destined to develop as either a male or a female embryo.
However, the fetal gonads and the external genitalia first develop through an indifferent stage, during which neither male or female characteristics are apparent. It is only as of the seventh week of gestation during which sexual differentiation of the organs begins. Note that an ultrasound of an embryo taken at this time will still not be able to distinguish the gender! That is because more time spanning weeks is required for the reproductive organs to further differentiate.
This article will help you understand the second chapter of the development of the urogenital system, as well as the different types of congenital anomalies that can occur when embryonic development does not go accordingly.
Overview
The development of the reproductive system includes the gonads, the genital ducts, the external genitalia, and the descent of the gonads.
- First, the gonads develop through an indifferent stage before differentiating into the testes and the ovaries.
- Second, the sexual differentiation of the genital ducts is dependent on the presence or absence of testosterone and Anti-Müllerian Hormone, which both influence the outcome of the mesonephric ducts and the paramesonephric ducts.
- Third, the sexual differentiation of the external genitalia is also dependent on hormonal secretions or lack of.
- Last, the descent of the gonads is mainly directed by the shortening of the gubernaculum.
Importantly, the development of the reproductive system is closely integrated with that of the urinary system. Both systems develop from a common mesodermal ridge along the posterior abdominal wall, while the excretory ducts of both systems terminate at a common cavity, the cloaca.
Gonads
The development of the human gonads is quite unique. For instance, the rudimentary lung can only differentiate into a lung and the rudimentary liver can only differentiate into a liver. However, the rudimentary gonads can differentiate into either the testes or the ovaries. Although the sexual differentiation of the gonads is genetically determined, the rudimentary gonads first develop through an indifferent stage, during which neither male or female characteristics are apparent. The formation of the indifferent gonads is only induced upon the arrival of the primordial germ cells.
During the fifth week of gestation, primordial germ cells migrate from the walls of the yolk sac (near the allantois) via the dorsal mesentery into each side of the posterior body wall. The primordial germ cells stimulate the coelomic epithelium to thicken, forming a pair of longitudinal ridges known as the genital ridges. These genital ridges, located ventromedial to the developing mesonephric kidneys, are the first physical appearance of both the male and female gonads.
During the sixth week of gestation, the surface epithelium of the genital ridge proliferates and gives rise to the primitive sex cords. These primitive sex cords, which are made up of somatic support cells, surround individual primordial germ cells. Note that the primitive sex cords remain connected to the surface epithelium. From this point on, the presence of a Y or X chromosome will dictate the subsequent sexual differentiation of the gonads. Thus, the undifferentiated gonads consist of a pair of genital ridges which contain primordial germ cells that are enveloped by the primitive sex cords.
Male
At the seventh week of gestation, the primitive sex cords continue to proliferate, extending deeper into the surrounding connective tissue. These cords then fuse to form a network of medullary sex cords known as the testis cords. These testis cords will eventually form a network of seminiferous tubules, which will only become canalized at puberty.
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Conversely, the extremities of the testis cords follow a slightly different path; they differentiate into thin-walled ducts known as the rete testis. Subsequently, the rete testis will connect with the mesonephric tubules, which will form the future efferent ductules. As the embryonic testes continue to develop, the surface epithelium becomes separated from the testis cords by a dense layer of fibrous connective tissue known as the tunica albuginea.
Female
In the absence of a Y chromosome (XX), the primitive sex cords do not continue to proliferate. Instead, they degenerate into irregular cell clusters. Concurrently, the primordial germ cells differentiate into oogonia, which proliferate and enter their first meiotic division to form primary oocytes. These meiotic oocytes stimulate the surface epithelium to give rise to a second generation of cords, the cortical sex cords. These cortical sex cords proliferate and split into clusters of follicle cells (or granulosa cells). Each oocyte then becomes surrounded by follicle cells and together, they form the primordial follicles of the ovary.
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Genital ducts
At the sixth week of gestation, both male and female embryos begin with two pairs of ducts: the mesonephric ducts and the paramesonephric ducts (or Müllerian ducts). The paramesonephric ducts are a second pair of ducts that appear lateral to the mesonephric ducts, concurrent with the arrival and differentiation of the primordial germ cells.
Similar to the mesonephric ducts, the paramesonephric ducts form in a cranial-to-caudal sequence. The caudal ends eventually adhere to each other and connect with the developing pelvic urethra of the urogenital sinus, just medial to the openings of both mesonephric ducts. The cranial ends open into the abdominal cavity as a funnel-like structure. From this point on, the presence or the absence of specific hormones will dictate the sexual differentiation of the genital ducts.
Male
At the seventh week of gestation, the differentiation of the male genital ducts is largely attributed by the presence of sertoli cells and Leydig cells. Sertoli cells secrete Anti-Müllerian Hormone (AMH) that stimulates the degeneration of the paramesonephric ducts. Leydig cells secrete testosterone to stimulate the further differentiation of the mesonephric duct and the mesonephric tubules.
The cranial mesonephric tubules connect with the rete testis and form the future efferent ductules, whereas the caudal ones degenerate. The mesonephric duct will eventually develop into the epididymis, the ductus deferens, the seminal vesicles, and the ejaculatory duct.
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Female
The differentiation of the female genital ducts is largely attributed by the absence of sertoli cells and Leydig cells. The mesonephric ducts and mesonephric tubules rapidly degenerate due to the absence of testosterone, whereas the development of the paramesonephric ducts remains uninhibited due to the absence of AMH. Additionally, the presence of estrogen further stimulates the development of the paramesonephric ducts. The cranial half forms the fallopian tubes and the funnel-like openings form the fimbriae. The caudal half that is connected to the urogenital sinus forms the uterus and the upper vagina.
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Conversely, the lower vagina develops from a different origin: the urogenital sinus. Specifically, shortly after the caudal ends of the paramesonephric ducts reaches the urogenital sinus, two solid evaginations known as the sinovaginal bulbs grow out of the sinus. Cells of the sinovaginal bulbs proliferate and form a solid vaginal plate. While the uterus and the upper vagina develop, the vaginal plate forms the lower vagina. Further cellular proliferation increases the length of the vagina and by the fifth month of gestation, it becomes completely canalized. The vagina thus has a dual origin, with the upper portion as well as the vaginal fornices derived from the paramesonephric ducts, and the lower portion derived from the urogenital sinus.
External genitalia
Similar to the gonads, the external genitalia also develop through an indifferent stage, during which neither male or female characteristics are apparent. Recall that the urorectal septum separates the urogenital sinus from the anorectal canal. While this occurs, the mesodermal layer surrounding the cloacal membrane expands and forms a pair of elevated cloacal folds.
Cranially, the cloacal folds unite and form the genital tubercle. Caudally, the cloacal folds become subdivided into the urethral folds anteriorly and the anal folds posteriorly. Surrounding the cloacal folds is another pair of elevations known as the genital swellings. Therefore, at its indifferent stage, the fetal external genitalia is made up of the genital tubercle, the urethral folds, and the genital swellings.
Male
Under the influence of the fetal testes, the genital tubercle becomes rapidly elongated, forming the phallus, whereas the urethral folds are pulled by the phallus to form the lateral walls of the urethral groove. The urethral folds start dorsally, grow toward each other, and connect ventrally to each other at the midline of the shaft. Upon closure, the urethral groove becomes converted into the tubular penile urethra. While both the genital tubercle and the urethral folds elongate, the genital swellings expand and fuse to form the scrotal swellings, the future scrotum.
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Female
In the absence of the fetal testes and their hormonal secretions, the genital tubercle does not lengthen and the urethral folds and the genital swellings do not fuse. Instead, the genital tubercle regresses and bends inferiorly to form the clitoris, whereas the phallic segment of the urogenital sinus forms the vestibule of the vagina. The urethral folds form the labia minora, while the genital swellings form the labia majora.
Descent of gonads
By the end of the second month of gestation, the gonads and the mesonephros are anchored to the posterior abdominal wall. With the degeneration of the mesonephros, the remaining mesentery forms the cranial suspensory ligament and the gubernaculum. The cranial suspensory ligament anchors the gonads to the diaphragm and the gubernaculum drives their descent towards the scrotum or the labia majora, the derivatives of the genital swellings.
Male
During the seventh week of gestation, the gubernaculum shortens and pulls the testes down to the vicinity of the deep inguinal ring, whereas the cranial suspensory ligament degenerates. The testes remain in this location between the third and seventh months before being further pulled by a shortening gubernaculum.
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Concurrently, the peritoneum of the abdominal cavity forms an evagination on each side of the midline into the ventral abdominal wall. This evagination known as the processus vaginalis, follows the course of the gubernaculum into the scrotum. Accompanied by the muscular and fascial layers of the anterior abdominal wall, the processus vaginalis forms the inguinal canal. The testes then become covered by the terminal and reflected fold of the processus vaginalis, forming the tunica vaginalis. Shortly after birth, the narrow canal connecting the tunica vaginalis to the peritoneal cavity becomes obliterated, while the gubernaculum becomes a small ligamentous band attaching the caudal pole of the testes to the scrotal floor.
Female
At seventh week of gestation, the gubernaculum becomes attached to the paramesonephric ducts. As the paramesonephric ducts migrate caudally to form the uterus and the upper vagina, they pull the ovaries into the peritoneal folds, which form the broad ligaments. In the absence of male hormones, the gubernaculum does not continue to shorten and instead persists as important anchoring ligamentous bands.
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The cranial half of the gubernaculum forms the round ligament of the ovary (or ovarian ligament), connecting the uterus to the ovary. The caudal half of the gubernaculum forms the round ligament of the uterus, connecting the uterus to the labia majora. In females, the cranial suspensory ligament persists and forms the suspensory ligament of the ovary.
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Clinical aspects
Uterus anomalies
Anomalies related to the development of the uterus are caused by abnormal fusion or regression of the caudal paramesonephric ducts. Recall that the caudal segments of the paramesonephric ducts fuse with each other to form the uterus and the upper vagina. Incomplete fusion of these caudal segments leads to the development of duplicated uterus with or without duplicated vagina.
Also, the uterine septum, being the transient structure that results from the fusion of these caudal segments, normally regresses. Failure of the uterine septum to regress leads to the development of bicornuate uterus (two uterine bodies and one cervix), a septated uterus (septum present in the uterine body), or a cervical atresia.
In instances when one paramesonephric duct completely regresses or fails to elongate during embryonic development, this leads to a unicornuate uterus (half a uterus). Although women with paramesonephric duct anomalies can conceive, they have higher rates of spontaneous abortion, premature delivery, and dystocia.
Male genitalia anomalies
Male genitalia anomalies such as hypospadias and epispadias are caused by incomplete fusion of the urethral folds. This results in an abnormal opening of the penile urethra that occurs along the ventral or inferior aspect of the penis; it could be located near the glans, along the shaft, near the base of the penis, or even along the scrotal raphe. This condition is known as hypospadias.
In instances in which the urethral opening is found on the dorsal or superior aspect of the penis, it is known as epispadias. Although epispadias can occur independently, it is usually associated with exstrophy of the bladder and an abnormal closure of the anterior abdominal wall.
Cryptorchidism
The failure of a single testis or both testes to descend into the scrotum is known as cryptorchidism. Although many infants may be cryptorchid at birth, the testes may spontaneously descend by three months of age. If the testes have not descended by four to six months of age, they are brought down surgically (orchiopexy).
Individuals with cryptorchidism have a higher risk of developing testicular cancer and can become irreversibly sterile. Testes located in the abdomen are usually three to five degrees warmer than if they were in the scrotum. This can reduce the number of adult type A spermatogonia available for spermatogenesis while increasing the likelihood of promoting germ cells into carcinoma cells.
Inguinal hernia and hydrocele
Recall that the connection between the abdominal cavity and the processus vaginalis in the scrotum normally becomes obliterated. If it remains open, intestines may descend into the scrotum and cause congenital indirect inguinal hernia.
In instances when the obliteration is incomplete, small fluid-secreting cysts may persist between the parietal and visceral layers of the tunica vaginalis, forming hydrocele of the testis and/or spermatic cord.
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