SEM_15_Reproductive system_PARTE1.docx

Reproductive system Learning objectives Describe the first indifferent stage of the reproductive system. Discuss how sex is determined in domestic animals. Describe the switch from the first bi-potential stage to the appearance of sex-specific organs in males and females; highlight which organs...

Reproductive system Learning objectives Describe the first indifferent stage of the reproductive system. Discuss how sex is determined in domestic animals. Describe the switch from the first bi-potential stage to the appearance of sex-specific organs in males and females; highlight which organs are homologous to each other. Describe the descent of the gonads and explain why it is important. Describe the development of the mammary gland. Consider briefly some abnormalities in the development of the reproductive system. Stages in sex differentiation https://sway.office.com/OqCVVhptwDvRDrvO#content=zA5Rmr64tCseww - Origin of the genital tract. The reproductive and urinary organs share a common origin from the intermediate mesoderm. The development of the sex-specific organs of the genital system is preceded by the formation of a set of temporary undifferentiated structures in the embryo. Sex differentiation is a complex process that includes the following distinct sequential stages: genetic, gonadal, hormonal, phenotypic and psychological. In mammals, genetic sex is established at fertilisation in which XY indicates male and XX denotes female. During the first period of development (two months of human gestation), the primordial genital structures are identical in the two sexes; this period is referred to as the indifferent stage. During this stage, the reproductive organs (gonads, internal and external genitalia) begin to develop as bipotential structures capable of forming either female or male sexual organs. At this indifferent stage, all embryos are potentially bisexual. In mammals, the sex-specific features start to develop at the end of the embryonic stage. In chromosomally male embryos (XY) the indifferent gonad will turn into a testis because a specific gene in the Y chromone called SRY gene (sex-determining region of the Y chromosome) is activated at a certain stage of development. This expression results in a cascade of events leading to the differentiation of specific male features: the indifferent gonad turns into a testis. In chromosomally female embryos (XX), the absence of the Y chromosome and SRY causes the indifferent gonad to complete its development according to a female pattern: the indifferent gonad turns into an ovary. When the indifferent gonads develop into either ovaries or testes, the gonad sex is established. It is the hormonal scenario determined by the type of gonad (testis or ovary), and thereby the presence or absence of androgens, what drives the sex-specific differentiation of the internal and external genital organs (phenotypic sex ). In other words, although genetic sex is inherited, the phenotypic sex is a consequence of the hormones released during embryonic development by the gonad. - Sex determination is a complex process influenced by genetic and environmental factors. The gonad The indifferent gonad is composed of two different cell populations: Supporting somatic cells arise from the coelomic epithelium that coats the gonadal ridge which proliferates and penetrates the underlying mesenchyme. Soon, the invading mesothelium and the disintegrating mesonephric tubules form the finger-like epithelial structures called gonadal cords. Primordial Germ cells (PGCs) differentiate at a very early stage of development (gastrula stage) when they can first be found among the epiblast. During gastrulation, they migrate through the primitive streak, and by the 3rd week, they reside in the endodermal wall of the yolk sac near the origin of the allantois. Then, they migrate along the wall of the allantoic stalk, gut and mesentery to finally reach the gonadal ridge where their arrival induces further gonadal development. In the gonadal ridge, the germ cells proliferate and migrate inside gonadal cords, where they become surrounded by supporting cells. Germ cells that fail to enter gonadal cords or are not surrounded by supporting cells suffer degeneration. In further development, these primordial germ cells differentiate either into male primordial germ cells (spermatogonia) or female primordial germinal cells (oogonia). https://sway.office.com/OqCVVhptwDvRDrvO#content=JhbQs6GSXNqySi - In the first indifferent stage of sex development, it is impossible to distinguish between male and female gonad. Male differentiated gonad: the testis If the embryo is genetically male (contains both sex chromosomes, X and Y chromosome), the signal for testis development is mediated by the SRY gene on the Y chromosome. Under the influence of this gene, the primordial sex cords continue to grow, proliferate and penetrate deeper and deeper into the medullary region. In male embryos, these enlarged gonadal cords are specifically referred to as seminiferous cords. Primordial germinal cells within seminiferous cords differentiate into spermatogonia which become dormant until puberty. At puberty, the immature seminiferous cords become canalised, forming the seminiferous tubules, which wall contains spermatogonia and supporting cells. Deep cords that lack germ cells become tubules of the rete testis, located centrally in the testis. In males, somatic cells differentiate specifically into supporting (Sertoli) cells. They secrete an inhibitory factor, the Anti-Müllerian hormone (AMH), also known as Müllerian-inhibiting hormone (MIH), that thwart the development of female ducts (Müllerian or paramesonephric ducts) and suppress spermatogenesis in immature testes. Under the influence of the seminiferous cords, mesodermal cells of mesonephric origin located between the cords differentiate into the interstitial (Leydig) cells, which produce androgen hormone: testosterone. In male embryos, the increased rate of testosterone secretion is responsible for the complete differentiation of the male genital ducts (Mesonephric or Wolffian ducts) and sex- specific external genitalia. Therefore, the embryonic differentiation of the male reproductive structures requires the secretion of testicular hormones. Müllerian-inhibiting substance (MIS), also named Müllerian-inhibiting factor (MIF) or anti-Müllerian hormone (AMH), produced by foetal Sertoli cells induces regression of the Müllerian ducts. Testosterone, produced by Leydig cells, promotes the development of Wolffian duct derivatives and masculinisation of the external male genitalia. Once the prenatal sex differentiation has been completed, testosterone production decreases until the onset of puberty. At this stage, a second activation of the Leydig cells population causes an increase in testosterone production, which is needed to complete the secondary sex maturation in males. The development of the testes includes the covering coelomic mesothelium which becomes the outermost layer or tunica vaginalis (an out-pocketing of the peritoneum); also, mesenchyme deep to the coelomic mesothelium becomes the tunica albuginea, a fibrous connective layer surrounding the testicular tissue. https://sway.office.com/OqCVVhptwDvRDrvO#content=i5avnfSu2oGyMR - Testicular development requires a cascade of gene activation and differentiation into different cell types. The first discernible event in testis development is the appearance of primordial Sertoli cells, which differentiate from somatic cells of the coelomic epithelium. Sertoli cells proliferate, aggregate around the primitive germ cells, and align into cordlike structures that subsequently become the seminiferous tubules. Another key event in testis development is the differentiation of steroidogenic Leydig cells differentiated from primitive interstitial cells of mesonephric origin. Female differentiated gonad: the ovary In the absence of Y chromosome (female embryos with two X chromosomes), the primordial gonadal cords stop growing and become irregular and disorganised at the end of the embryonic stage when the ovary starts to differentiate. In the central region of the ovary, the sex cords disappear completely and are replaced by a vascular stroma that forms the ovarian medulla. In the cortical region, the gonadal cords that remain close to the surface are dismantled and their constituents (primordial germinal cells and supporting cells) are reorganised to form the primordial follicles. In female embryos, the primordial germinal cells differentiate into oogonia, which undergo a prenatal period of enhancing mitotic activity. The female supporting cells differentiate into the follicular cells, also called granular cells, which surround each oogonium as a single-layered cuboid epithelium. Each oogonium with the associated layer of cuboid follicular cells constitutes a primordial follicle. In developing ovaries, the entire population of oogonia enters the first meiotic division, but this division stops at the prophase stage. In the second third of gestation, the entire population of oogonia is already contained in primordial follicles (with a single layer of cuboid follicular cells). In mammals, a high percentage of oogonia and primary oocytes undergo degenerative changes referred to as atresia, during prenatal and postnatal life. At birth, the ovaries of mammals already have a reserve of primordial follicles, the number of primordial follicles (follicular reserve) is a determining factor in the reproductive life of females, as well as their fertile life. Beginning in publerty, in each estrous cycle, a number of ovarian follicles develop, secrete hormones, and then end up either stressing or ovulating. In contrast to the embryonic development in males, female differentiation does not require specific hormone exposure: female differentiation just happens in the absence of testicular hormones and is irrespective of the genetic sex. At puberty, when ovulation starts to happen, the female reproductive organs are exposed for the first time to an increased level of oestrogen produced by the growing follicles. This oestrogen exposure is required to complete the female secondary characteristic. https://sway.office.com/OqCVVhptwDvRDrvO#content=WZ4iD1QIyKYo6I - Ovarian development is the default pathway, while testicular development is dependent on the expression of the SRY gene. In the ovary, the gonadal cords dissolve - also in the cortex - due to blood vessels that are sprouting from the medulla and the oogonia become surrounded by a monolayer of cells that have differentiated out of the gonadal cord cells and now are now called follicular cells or granulosa cells. The primary oocytes that are enveloped by follicle cells are now designated primordial follicles. The undifferentiated genital ducts At the indifferent stage, embryos are potentially bisexual: both sexes have the primordia of male and female genital ducts. On one hand, the embryo has the mesonephric (Wolffian) ducts which persist for some time after the mesonephros disintegrated. On the other hand, a pair of paramesonephric (Müllerian) ducts develop along the ventrolateral coelomic surface of the mesonephros. They begin as a groove, then become a core of cells, and subsequently, they canalise and elongate. The development of the male’s genital tract and external genitalia is dependent on the testicular hormones. In contrast, the development of the female’s genital tract and external genitalia is predetermined in the absence of testicular influence. Although some recent evidence indicates that female genital development is not a completely passive process. - In the undifferentiated stage, two precursor organs exist in the embryo: the Wolffian ducts (mesonephric ducts), which differentiates into the structures of the male genital tract, and the Müllerian ducts (paramesonephric ducts), the source of the female reproductive organs. The female genital ducts It is generally accepted that the female differentiation is the pattern by default: it just happens in the absence of testicular hormones irrespectively of the genetic sex. In other words, the paramesonephric (Müllerian) ducts develop into the female genital ducts without any hormonal requirement at the same time that the mesonephric (Wolffian) ducts degenerate if testosterone is not produced by the gonad (embryo female scenario). The cranial part of the paramesonephric ducts gives rise to the uterine tubes which open to the coelomic cavity next to the ovaries. The middle portion of the paramesonephric ducts becomes the uterine horns. Further caudally, the bilateral paramesonephric ducts shift medially and fuse into a single tube that ends blindly in contact with the urogenital sinus. The single fused duct become the uterine body, uterine cervix, and the cranial third of the vagina. The length of the paramesonephric ducts that become fused is species-dependent. Among domestic mammals, fusion is greater in horses (short uterine horns) than in carnivores (large uterine horns). In primates, human included, fusion normally produces a uterine body without horns. In contrast, rodents and rabbits have a double uterus with two cervices entering a single vagina. Monotremes and many marsupials have a double vagina with no fusion at all. Occasionally, remnants of the embryonic mesonephric ducts can be found in the wall of the vaginal vestibule in females (Gartner's duct). Occasionally, these remnants may give rise to the formation of Gartner's duct cysts. https://sway.office.com/OqCVVhptwDvRDrvO#content=4qqI3FSGsYVEIP - In females, in the absence of MIS, the Müllerian ducts become the uterus, cervix, upper third of the vagina, and the Fallopian tubes. Because testosterone is required for the development of the Wolffian ducts, in its absence they atrophy. The male genital ducts The sexually bipotent embryo turns into the male pattern only if the indifferent structures are exposed to testicular hormones: testosterone produced by the testicular interstitial cells (Leydig cells) makes the mesonephric ducts to thrive, while paramesonephric ducts (potential embryonic female ducts) are suppressed by the Müllerian inhibiting hormone released by sustentacular cells (Sertoli cells). Occasionally, remnants of the female embryonic ducts may persist after birth, giving rise to the development of congenital Mullerian cysts. Under the influence of testosterone, the mesonephric tubules included inside the gonad become efferent ducts. They connect the rete testis with the cranial part of the mesonephric duct, which becomes the epididymis. The middle and caudal portions of the mesonephric ducts become the ductus deferens, which conveys sperm to the part of the urogenital sinus that becomes the pelvic urethra. Development of secondary sexual glands is also testosterone-dependent. They arise as an endodermal outgrowth from the wall of the urethra (prostate and bulbourethral glands) or from the final part of the mesonephric ducts (vesicular glands, a.k.a seminal vesicles). Like in other organs, supportive tissues and smooth muscle are contributed from the surrounding mesenchyme. Some species-specific differences in the development of secondary sexual glands are: cats lack seminal vesicles, and dogs only develop prostate gland. https://sway.office.com/OqCVVhptwDvRDrvO#content=htDSgLxX5AaQCp - In males, the newly formed testes produce testosterone, which stimulates the differentiation of the Wolffian ducts into the epididymides, vas deferens, and the seminal vesicles while MIS, also known as an anti-Müllerian hormone, is secreted by the fetal Sertoli cells and ablates the Müllerian ducts The descent of the testes In most mammals, testes migrate from their site of development in the roof of the abdominal cavity to an external sac in the inguinal region (scrotum). This extra-abdominal position ensures a temperature of 2-4 Cº below the core body temperature, which is required for normal spermatogenesis. Alternatively, in aquatic mammals, elephants and other vertebrate animals, testes remain within the abdominal cavity. In some extent, ovaries may undergo a similar displacement, but ovaries must always remain in an intra-abdominal position; the extent in which ovaries move from their original position is species- dependent (e.g., a slight caudal displacement in bitches vs. a wide descent toward the pelvic floor in cows). Gonads are attached to the abdominal wall by ligaments. One of them is the gubernaculum testis, a condensation of mesenchyme that runs along the lateral wall of the body, linking the gonad to the inguinal region. The gubernaculum testis results in an essential structure to accomplish successfully the descent of the testes. In males, under the influence of the testosterone, the gubernaculum accumulates fluid and becomes a jelly-like cord as large in diameter as the testis. The swollen gubernaculum keeps a canal open on the floor of the body wall (inguinal region) where the scrotum, a sack of skin, bulges on the ventral surface. Through this inguinal canal, an evagination from the coelom, called vaginal process, is pushed into the scrotum. Under the guidance of the gubernaculum testis, subsequent growth and elongation of the body move the testes down, toward the inner opening of the inguinal canal. A sudden increase in the intra-abdominal pressure pops the testis through the inguinal canal into the scrotum. Whether the testis is actively pulled by the gubernaculum into the scrotum or the gubernaculum is just a guiding structure, is still a matter of discussion. In humans, pigs, ruminants and cats, testis descent should be completed before birth. In horses, the testes descend into the scrotum between 30 days before and 10 days after birth; when examining a neonate foal, it should be considered that the gubernaculum testis remains quite large at birth in this species and it can be easily mistaken for the testis. In dogs, testes descend postnatally; dog testes usually descend by ten days of age and individuals are considered cryptorchids if the testicles are not descended by the age of eight weeks. https://sway.office.com/OqCVVhptwDvRDrvO#content=2Ol1D1L3cTQ9eT - The appropriate differentiation of the gubernaculum testis is an essential requirement to accomplish successfully the descent of the testes. Failure of normal testicular descent is referred to as cryptorchidism. Cryptorchidism is a failure of one or both testicles to descend into the scrotum. It is seen in all domestic animals; it is common in stallions and boars and is the most common disorder of sexual development in dogs (13%). Cryptorchidism is caused by a combination of genetic, epigenetic, and environmental factors. Bilateral cryptorchidism results in sterility. Unilateral cryptorchidism is more common, and the male is usually fertile because of sperm production from the normally descended testicle. The undescended testicle may be located anywhere from just caudal of the kidney to within the inguinal canal and can be identified by trans-rectal or trans-abdominal ultrasonography. Abdominal testicles produce male hormones, and cryptorchid animals have normal secondary sex characteristics and mating behaviour. Cryptorchid testicles are more prone to problems such as torsion and cancer. Neutering, which is surgically removing the testicles, can prevent these problems from occurring. - Cryptorchidism is the medical term that refers to the failure of one or both testes (testicles) to descend into the scrotum. External genitalia Undifferentiated stage External genitalia is derived from three different perineal swellings found in both sexes around the external opening of the urogenital sinus: Urogenital folds. These bilateral folds border the urogenital orifice. Genital tubercle. It develops ventrally where the urogenital folds meet. Genital or labioscrotal swellings. They are located lateral to the urogenital swellings. https://sway.office.com/OqCVVhptwDvRDrvO#content=yfYvrFEcgETZK9 - External genitalia is initially identical and undergoes male and female differentiation under the influence or absence of steroid sex hormones. Male external genitalia Under the influence of testosterone (male scenario), the genital tubercle keeps growing to generate an elongated phallus or penis. Mesenchyme inside the genital tubercle gives rise to the specific components of the phallus, such as the erectile tissue, connective tissue, smooth muscle, and bone (carnivores). The urogenital orifice and urogenital folds elongate ventrally along the phallus forming a urogenital groove. Soon after, the urogenital groove closes in proximal to distal sequence to form the penile urethra. The penile urethra opens into an ectodermal invagination at the distal end of the original genital tubercle which forms the glans of the penis. The genital swellings turn into the scrotum, which too has a midline fusion, the raphe. The scrotal sac is initially empty until the descent of the testes begins. https://sway.office.com/OqCVVhptwDvRDrvO#content=pxEztQ3XhQ9nH4 - In males, the urogenital folds beneath the genital tubercle begin to fuse in the midline to form the penile urethra.The genital swellings give rise to the scrotum. Female external genitalia In the absence of testosterone (female scenario), the genital tubercle involutes and becomes the clitoris. The urogenital orifice becomes the opening of the vulva (vulvar cleft), which is in direct communication with the vaginal vestibule (derived from the urogenital sinus). The urogenital folds elongate, overgrow the genital tubercle and become the labia of the vulva, equivalent to the labia minora in primates. In most domestic mammals, the genital swellings become flat and disappear. Only in some species (primates and horses), the genital swellings persist to form the labia majora of the vulva. https://sway.office.com/OqCVVhptwDvRDrvO#content=Ng1uxU5E64lUnP - In females, the urogenital folds beneath the genital tubercle remain separate (unfused), forming the inner labia minora and second outer skin folds form the larger labia majora either side of the developing vestibule of the vagina. The genital tubercle changes in size as it forms the glans of the clitoris.