Session 1: Origin of the Sexes Flashcards
Introduction
- Human reproduction is sexual. New diploid individuals arise from the fusion of 2 haploid gametes – one from a female (the ovum) and one from a male (the sperm).
- The conceptus develops into an embryo and then fetus within the female reproductive tract nurtured via a placenta.
- Birth (parturition) occurs at a relatively advanced stage of development, and adults then care for the offspring for a long period until puberty, when sexual maturity is achieved.
- Most human pregnancies yield only one neonate, and the number of young produced in a female’s (relatively long) reproductive life span is generally small. Sophisticated mechanisms involving most systems of the body have evolved to maximise the chance of reproductive success.
Describe the formation of the gametes
[*] Gametes form from diploid germ cells.
[*] Germ cells separate off from the other cells of the body – somatic cells – very early in development and find their way to the primordial gonads, which develop into the female and the testes in the male.
[*] In a complex interaction with somatic cells of gonad, the germ cells first multiply by mitosis then undergo meiosis to form haploid gametes. Then the germ cells cyto-differeniate into mature gametes.
[*] (The primordial germ cells are formed in the epiblast during the second embryonic week).
[*] The germ cells are a special population; “seed” for the next generation
[*] Germ cells are identifiable in the embryo from 3-4 weeks post-conception. They arise in the epithelium of the yolk sac near the base of the developing allantois migrate into the retroperitoneum, along the dorsal mesentery as the embryo folds.
What determines genetic sex?
[*] The chromosomes of their germ cells determine the genetic sex of an individual (females have XX, male XY).
[*] Male germ cells make sperm, female germ cells make ova.
[*] The rest of the embryo can be male or female. In normal development, the genetic sex of the germ cells determines phenotypic sex.
What has happened by six weeks post-conception?
By six weeks post conception germ cells have migrated to the primordial gonads (somatic mesenchymal tissue), which are superficial and medial to the mesonephric tissue. Columns of cells from the mesonephros and coelomic epithelium form the primitive medullary cords and sex cords, respectively.
What happens if the germ cells are male?
[*] If the germ cells are male (the primordial germ cells carry the Y chromosome), there is vigorous growth (colonisation) of the sex cords into the medullary region of the gonad to meet the mesonephric cords, and so form the definitive testis cords.
- The germ cells enter these cords, which will in the adult give rise to seminiferous tubules within which sperm will be formed. The mesodermal cells give rise to Sertoli cells. Sertoli cells express a gene – the SRY gene – which is expressed only in males.
Expression of SRY genes drives development of male
- Gonad (testis)
- Internal genitalia (duct system)
- External genitalia
What happens if the germ cells are female?
[*] If the germ cells are female (the primordial germ cells do not carry Y chromosome), the medullary cords do not develop (due to absence of the Y chromosome – no expression of the SRY genes).
- The cortical region of the gonad develops. Germ cells colonise the gonadal cortex after migrating through the developing embryo to the primordial gonad.
- The germ cells become surrounded by mesenchymal cells to form primordial follicles. The germ cells – now oogonia – are surrounded by a single layer of granulosa cells. Absence of Y chromosome leads to development of female
- Gonad (ovary)
- Internal genitalia (duct system – i.e. tubes and uterus)
- External genitalia
What happens if no germ cells arrive?
[*] If no germ cells arrive the development of primitive sex cords is not initiated, therefore no gonadal ridges form and consequently mature gonads do not develop.
Describe the necessity of the female internal and external genitalia
The female: the necessity to nurture the embryo and fetus limits the number of female gametes that can be produced. Unless pregnant, a woman of reproductive age will produce 12-14 ova per year, a total of about 400 over a reproductive life-span of nearly 40 years from puberty to the menopause.
[*] Ova are capable of fertilisation by sperm for about 36 hours after they are released from the gonad (‘ovulation’), so in practice a woman is fertile for only a few days a year. To maximise the chance of conception and the survival of the conceptus, each ovulation is embedded in a reproductive cycle of events in the gonads, reproductive tract and the rest of the body.
[*] The female external genitalia provides a means of introducing sperm to the female reproductive tract and the formation of a birth canal through which the foetus may be delivered.
[*] Secondary sexual characteristics develop at puberty to facilitate sexual interaction.
- Female Internal Genitalia:
[*] Ovaries
[*] Uterine tubes/Fallopian tubes
[*] Uterus
[*] Cervix
[*] Vagina
- Female External Genitalia
[*] Vagina
[*] Vestibule
[*] Labia majora
[*] Labia minora
[*] Clitoris
Describe the male internal and external genitalia
The male: to exploit intermittent female fertility the male must be continuously fertile. Only a tiny proportion of male gametes will survive the journey through the female tract, so very large numbers must be produced. A young man will produce about 7000 sperm a second.
[*] Male internal genitalia collect and mature this continuous sperm production and produce the other components of semen, which is the vehicle in which sperm are introduced to the female tract.
[*] Male external genitalia deliver the semen, which is ejaculated into the vagina during coitus.
- Male Internal Genitalia
[*] Testis
[*] Epididymis
[*] Ductus deferens
[*] (Urethra)
[*] Seminal glands
[*] Ejaculatory ducts
[*] Prostate
[*] Bulbourethral glands
- Male External Genitalia
[*] Glans penis
[*] Shaft of Penis
[*] Scrotum
What is meant by the indifferent state?
The production of gametes and the mechanisms of gestation and parturition are co-ordinated by hormones. The hypothalamus, anterior and posterior pituitary gland, the gonads, and the placenta produce hormones that are involved in reproductive processes. Many other hormones are involved to a lesser degree in reproductive processes as they affect virtually every body system.
- At six weeks post conception, the embryo has primordia for both male and female internal genitalia. “Indifferent state” which then leads to the development of the gonad and duct system. Developmental “cross-roads”, regulated by genetic sex.
- Mesonephric ducts develop in both male and female embryos. Paramesonephric ducts develop in both male and female embryos (appear near to the mesonephric ducts). Both the mesonephric and paramesonephric ducts ends at the cloaca.
[*] Mesonephric tubules have a primitive renal function (stimulates the development of the true kidney).
[*] Mesonephric tubules + mesonephric duct = embryonic kidney
[*] Mesonephric duct runs caudally to make contact with the cloaca
[*] The urogenital sinus is created from hindgut by urorectal septum and it is continuous with the umbilicus
Describe the mesonpehric and paramesonephric ducts
- Male internal genitalia form from the Wolffian or mesonephric ducts. Expression of the SRY genes serves to maintain the mesonephric ducts after it has made a separate opening along with the ureteric buds into the urogenital sinus, even though the mesonephric ducts are no longer needed by the embryonic kidney. The prostate and prostatic urethra form under the influence of testis-derived Androgen hormones.
- The paramesonephric ducts (aka Müllerian ducts) appear as invaginations of the epithelium of the urogenital ridge. They run along the entire embryonic trunk, parallel to the mesonephric ducts. It caudally makes contact with the cloaca (urogenital sinus) and its cranial end opens into the abdominal cavity (‘open-duct system’)
[*] The paramesonephric ducts grow and extend into the peritoneal cavity, dragging the peritoneum and gonads. They move towards each other in the midline – fuse together.
[*] 2 discrete ducts fuse together to form a patent structure with a lumen where future uterus and fallopian tubes will develop.
How do the male and female internal genitalia develop?
- Structural development occurs in utero. Functional development and maturation continues after birth – through puberty (sexual maturation, secondary sexual characteristics develop)
- In the female, the Wolffian ducts regress spontaneously (due to the tiny amounts of Androgens which are insufficient to maintain the ducts) The Müllerian duct develops into oviducts (fallopian tubes), uterus, cervix and upper third of the vagina. If there are no gonads at all, the Müllerian ducts develop.
- In the male, the Sertoli cells secrete Müllerian Inhibitory Hormone (MIH) and interstitial cells secrete testosterone. As a result the Müllerian ducts regress and the Wolffian ducts develop. The seminiferous cords join the mesonephric (Wolffian ducts) at the rete testis, and the reminder of each duct forms the epididymis, vas deferens and seminal vesicles.
Is the vagina mesoderm or endoderm derived?
[*] The vagina has a contribution from both mesoderm and endoderm due to the interaction between the paramesonephric ducts.
The prostate develops from the urogenital sinus in the male under the influence of testosterone but the pelvic part of the urogeital sinus forms the inferior two thirds of the vagina in females.
Describe the development of the male and female external genitalia. What are the basic components? What do they go on to develop in each sex?
[*] Like the gonads, the primordial of the external genitalia are bi-potential
[*] Basic components:
- Genital tubercle (GT)
- Genital folds – surround the exit of the urogenital sinus
- Genital swellings
[*] In the female, the urethral folds and genital swellings form the labia minora and majora, and the genital tubercle forms the clitoris. This pattern of development occurs without hormonal stimulation. No fusion occurs – the urethra opens into the vestibule. No elongation of the genital tubercle.
[*] In the male, Androgens secreted by the testis cause the urethral folds to close, forming the shaft of the penis including spongy urethra; the genital swellings fuse to form the scrotum, and the genital tubercle to expand (elongates) to form the glans penis.
Dihydrotestosterone is very potent!
Describe the descent of the testis. What is the gubernaculum?
[*] the testis arises in the upper lumbar regions. It is tethered to labioscrotal folds (future scrotum) by the gubernaculum. The gubernaculum is attaches to the caudal end of the testis. As the body grows, the relative position of the testis becomes more caudal as the gubernaculum ligament effectively shortens as the trunk elongates. The testis is retroperitoneal and descends behind the peritoneum.
A musculo-fascial layer evaginates into the scrotum as it develops, together with peritoneal membrane to form the processus vaginalis.
Between 25 and 28 weeks of gestation, the testis migrates over the pubic bone behind the processus vaginalis (normally loses patency)
It reaches the scrotum by 34-40 weeks and is surrounded by the processus vaginalis which is itself within the gubernaculum.
Above the testis the fascia and peritoneum becomes closely apposed.
The fascial layers, obliterated stem of the processus vaginalis, vas deferens, testicular vessels and nerves, form the spermatic cord which occupies the inguinal canal in males.
The scrotal ligament is the vestigial remnant of the gubernaculum in the male (lower part only). The scrotal ligament secures the testis to the most inferior portion of the scrotum, tethering it in place and limiting the degree to which the testis can move within the scrotum.
Describe the descent of the ovaries?
[*] the ovaries also undergo an albeit less dramatic caudal shift in position from their origin on the posterior abdominal wall. The ovary descends to the pelvis. Doesn’t descend as far because it encounters mechanical obstruction (by the uterus)
- The gubernaculum attaching the ovary inferiorly to the labioscrotal folds becomes the ovarian ligament (connecting ovary to uterus) and the round ligament of the uterus (connecting the uterus to the labia).
- Therefore, the round ligament is the only structure occupying the inguinal canal in females.
What are the male secondary sexual characteristics?
[*] Increased body size (relative to females) including increased laryngeal size
[*] Deepening of voice
[*] Changes in body composition and fat distribution – increased bone mass, increased skeletal muscle strength and mass
[*] Changes in hair and skin – thickened skin, increased and thickened hair on the trunk, pubis, axillae and face
[*] Facial hair, male pattern baldness
[*] Central nervous effects (underpin behavioural changes)
[*] Smell
[*] All due to the presence of male sex hormones
What are the female secondary sexual characteristics?
[*] Decreased body size (relative to male)
[*] Subcutaneous fat distribution in thighs and hips (preparing female – to support foetus during gestation and lactation)
[*] Hair and skin changes
[*] Breast development
[*] Central nervous effects
[*] Uterine enlargement, enlargement of the labia minora and majora, pubic hair, cornification (keratinization) of the vaginal mucosa
[*] All due to the absence of male sex hormones
What are some examples of structural defects? What is Cryptorchidism?
Structural defects
[*] Cloacal portioning defects
[*] Hypospadias
[*] Uterine structural defects
Cryptorchidism: an undescended testis is the most common genital abnormality seen in male newborns. Either one or both testes may be involved.
[*] Occurs when the gubernaculum either fails to develop or fails to pull the testes into the scrotum.
[*] Androgen activity directs gubernacular development and function, thus gubernacular dysfunction reflects androgen abnormalities.
[*] Cryptorchid testes may remain in the inguinal canal (70%), the abdomen or retroperitoneum (25%) or other ectopic locations.
[*] Testes remaining in the abdomen or inguinal canal will be exposed to comparatively higher temperatures than those of the scrotum and will cease spermatogenesis in response. They are also prone to neoplastic change. Medical therapy for cryptorchidism involves administration of hCG or androgens. Surgical therapy is called orchiopexy.
Describe how the testes drain to the epididymis
The testes (testicles) are paired ovoid reproductive glands suspended in the scrotum, by the spermatic cords. Surrounded by a capsule, each testis consists of a number of seminiferous tubules (ST) which drain via the straight tubules into the rete testis (R) (‘collecting vessels’). From here, the efferent ductules (DE) lead to the epididymis which is highly coiled. Plastered onto the posterior aspect of the testis (sngl.), the epididymis is described as having a head (H), body (B) and tail (T)
Describe the outer layer of the testis
A section through the edge of the testis shows it to be covered by a tough fibrous, connective tissue covering called the tunica albuginea. The tunica albuginea thickens into a ridge on its internal, posterior aspect as the mediastinum of the testis. From this internal ridge, fibrous septae (walls) extend inward between lobules of long and highly coiled seminiferous tubules, in which sperms are produced.
Beneath the outer tunica and the seminiferous tubules (ST) a vascular layer, the tunica vasculosa, is found.
Describe the 2 layers of the tunica vaginalis
The surface of each testis is covered by the visceral layer of the tunica vaginalis, except where the testis attach to the epididymis and spermatic cord. The parietal layer of the tunica vaginalis is adjacent to the internal spermatic fascia, is more extensive than the visceral layer and extends superiorly for a short distance onto the distal part of the spermatic cord. There is a small amount of fluid between the two layers, in the cavity of the tunica vaginalis, allowing the testis to move freely in the scrotum.
- Sertoli cells are located within the epithelium of seminiferous tubules and involve in spermatozoa development
- Leydig cells are in the interstitial tissue and secrete testosterone.
- The tubules are separated from the surrounding interstitial tissue by the blood testis barrier.
Describe the pre-antral follicle stage
Primordial to pre-antral: the primary oocyte grows dramatically but does not re-start meiosis. Development occurs independent of hormones.
[*] The follicular cells change from flat to cuboidal cells, before proliferating to form multi-layered epithelium called the granulosa cells.
[*] Granulosa cells secrete glycoprotein to surround the primary oocyte with a zona pellucida.
[*] Surrounding stromal (connective tissue) cells form a theca folliculi with 2 parts: an inner theca interna that is vascular and endocrine, and an outer theca externa which is a fibrous capsule.
[*] Theca and granulosa cells collaborate to secrete oestrogens.
Describe the formation of a secondary follicle
The antral transition to form an antral, or secondary follicle
[*] Granulosa cells continue to proliferate, and a fluid appears between them, eventually forming the antrum (fluid-filled space).
[*] As more fluid forms, this secondary or Graafian follicle expands dramatically. In humans, antral follicles expand to 2mm diameter without stimulation by reproductive hormones, but continued development depends upon follicle stimulating hormone which binds only to granulosa cells, and luteinizing hormone which binds only to thecal cells.
[*] In each cycle, only one follicle normally becomes dominant and develops further – grows to 20 mm.
[*] Under the influence of luteinizing hormone, thecal cells secrete androgens. Androgens are converted to oestrogens by the granulosa cells under the influence of FSH.
Describe the formation of a pre-ovulatory follicle
[*] This phase begins 37 hours before ovulation.
[*] Under the influence of oestrogen, receptors for LH appear on the outer granulosa cells. These are stimulated by an LH surge leading to rapid changes in the follicle – LH surge triggers rupture of the follicle
[*] Within 3 hours of the LH surge, the oocyte re-starts meiosis and the first meiotic division is completed. This division is asymmetric; cytoplasm remains with one daughter, the other forms a condensed polar body.
[*] The secondary follicle enters meiosis II and then arrests again, 3 hours prior to ovulation. So first division is completed before ovulation but not second.
[*] Follicle size increases dramatically by increase in antral fluid volume (full size being 25mm) and the structure begins to weaken. LH stimulates collagenase activity leading to follicle rupture.
[*] The ovum is carried out in the fluid and gathered up into the fallopian tube by fimbria.
[*] Meiosis is not completed (second division is not completed) until the ovum is fertilised
[*] Unfertilised cells degenerate 24 hours after ovulation)
What is meant by ovulation and when does it occur?
- Ovulation involves expulsion of the egg through a thinned-out area known as the stigma.
- Once the oocyte is released, the follicle collapses and the granulosa cells proliferate to fill the space left by the oocyte and its associated follicular fluid.
- They undergo transformation into plump, endocrinologically active cells known as lutein cells. The lutein cells produce a yellow pigment and the structure containing these cells is appropriately called the corpus luteum (yellow body).
- During corpus luteum formation, blood vessels penetrate the follicular basement membrane.
- Ovulation occurs about midway through the menstrual cycle, after the follicular phase, and is followed by the luteal phase. Ovulation is characterised by a sharp spike in levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), resulting from the peak of oestrogen levels during the follicular phase.
Give a summary of spermatogenesis
The process whereby spermatogonia are converted into mature sperms is divided into three phases:
SPERMATOCYTOGENESIS (or spermatogenesis)
MEIOSIS
SPERMIOGENESIS
The fact that the Type A(d) spermatogonia divide into both dark and pale spermatogonia during mitosis ensures that there is always a supply of stem cells to form new spermatocytes.
Each primary spermatocyte contains 22 pairs of chromosomes and two sex chromosomes. In the first part of the first meiotic division (S phase) there is synthesis of DNA to produce a cell containing the normal number of chromosomes but double the amount of DNA. At the end of the division this cell divides producing a secondary spermatocyte containing 22 chromosomes plus one sex chromosome and the normal amount of DNA.
[*] The second meiotic division has no S phase and hence the spermatid that is produced at the end of the division contains only half the normal complement of DNA and chromosomes
