Sex differentiation and gametogenesis Flashcards

1
Q

Sex differentiation and gametogeneis

What defines sex?

A
  • Sex
    -Gender
    -Sexuality
  • Genotypic sex
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2
Q

What is genotypic sex?

A
  • Established at fertilisation
    -determined by Y chromosome
  • Female genotypic sex = default sex unless chromosome dictates a male trajectory
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3
Q

What are some examples of altered chromosome dosages (non-disjunction during gametogenesis)?

A

XO - Turner syndrome: Female, sterile, poorly developed breasts and mimature sexual organs
XXY - Klinefelter syndrome : Male, above average height, underdeveloped testes, occasional breast development

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4
Q

What is gastrulation?

A
  • An early developmental process in which an embryo transforms from a one-dimensional layer of epithelial cells, a blastula, and reorganizes into a multi layered and multidimensional structure called the gastrula
  • Ectoderm - outermost layer and differentiates into skin, brain, spinal cord and nerves
  • Endoderm- forms the innermost layer and gives rise to the digestive and respiratory systems, Urinary bladder and middle part of the ear.
  • Mesoderm - forms the middle layer and differentiates into a notochord, muscles, heart, blood vessels, kidneys, gonads etc.
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5
Q

What are Primordial Germ Cells (PGCs)

A
  • the primary undifferentiated stem cell type that will differentiate towards gametes: spermatozoa or oocytes.
  • characterised by high electron cytoplasm density and have a very irregular outline
  • Ectoderm - forms the outermost layer and differentiates into skin, brain, spinal cord and nerves
  • Endoderm-forms the innermost layer and gives rise to the digestive and respiratory systems, urinary bladder and middle part of the ear
  • Mesoderm - forms the middle layer and differentiates into a notochord, muscles, heart, blood vessels, kidneys, gonads etc.
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6
Q

How are PGCs identified?

A
  • according to their structural (morphological) properties; round, oval shapes, large sizes, large nucleus , marked nuclear membrane and the typical electron dense structures
  • high electron cytoplasm density and irregular outline
  • Have a diameter of 10-20 micrometres depending on species, stage and shape,
  • peripheral cytoplasm = high alkaline phosphate activity (indicator enzyme)
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7
Q

Outline the development of PGCs.

A
  • Around week 4 - differentiation of PGCs occurs from epiblast-derived cells present in the yolk sac near the base of the allantois
  • By 5 weeks, PGCs migrate along the dorsal mesentery of the hind gut to the gonadal ridges and establish the bipotential/undifferentiated gonad
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8
Q

How do the testis and the ovaries develop from the PGCs?

A

Testis - develops from the medulla of the indifferent gonad; the cortex regresses
Ovary - develops from the cortex of the indifferent gonad; the medulla regresses

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9
Q

What is the sex determing region on the Y Chromosome ?

What does it determine and where is not expressed?

A

Not expressed - Female (default sex?)
- pre-setoli - SRY - Sox-9 (+FGF-9) – Testicular differentiation (AMH) and/or ovarain factor block (FOXL2?; WNT4)

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10
Q

sex differentiation and gametogenesis

What is Gondal differentiation?

What does the gonad develop into? What is this in response to? When does this happen? What happens when this is not present? What develops instead?

A
  • Indifferent gonad develops into a testis in response to Testis Differentiation Factor (TDF) before week 9 of developmeny?
  • An ovary will develop instead if TDF is not present
  • -
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11
Q

Which hormones is male-pattern sexual differentiation dependent on?

3 different types

A
  • Testosterone
  • DHT (dihydrotestosterone)
  • Anti-mullarian hormone (AMH)
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12
Q

What hormones do testis directly produces both testosterone and AMH.

A
  • Produces both testosterone and AMH. Peripheral tissues convert testosterone to DHT.
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13
Q

What is the different in having AMH and no AMH?

A
  • AMH (Testes — PreSertoIi = Male)
  • Müllerian — involution
  • T4 — development Wolffian (eyaculatory
    tubular system)
  • Rete testis, efferent tubules, epididymis,
    vas deferens, accessory glands.
  • No AMH (Ovary = Female)
  • Müllerian — elongation = Oviduct;
    Uterus (fusion); Cranial vagina (BMP-4)
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14
Q

What is Testicular differentiation?

A
  • Cord formation at week 7:
  • PGC within tubular structures (spermatic cords)
  • Sertoli cells - within cords
  • support for spermatogenesis (puberty)
  • Number increases: infancyy (FSH)
  • After formation - arrested until peri-puberty - onset of spermatogenesis in response to rising testosterone
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15
Q

What do PGCs induce in male embryos/

A
  • induce maturation of primitive sex cord structures, whichbecome hollowed out and develop into the seminiferous tubules
  • give rise to spermatogonia, the first cells in the pathway to sperm.
  • form the rete testis, a system of interconnected tubules creating an outlet for sperm.
  • The cortex regresses to form a thin epithelial layer.
  • Mesenchymal cells take up residence among the sex cords and eventually become the Leydig cells testis.
    At around the 10th week of development, the Leydig cells respond to fetal pituitary and placental hormones (mainly human chorionic gonadotropin) by producing testosterone, which influences the differentiation of the external genitalia.
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16
Q

What is the process of ovarian differentiation?

A
  • The medulla of the gonad regresses while the cortex becomes greatly thickened, due to mitotically dividing PGCs, which give rise to oogonia.
    -By week 8 the developing ovaries contain around 600,000 oogonia, increasing to 6 to 7 million by week 20.
  • While a large number of oogonia die and become resorbed, the remainder become surrounded by a single layer of granulosa cells to form primordial follicles.
  • By week 20 , all the oocytes are arrested at prophase I of meiosis and remain in
    that state until the follicle is selected for maturation or death later in life.
  • At birth, each ovary holds around 1 million primordial follicles. This is all that will be available for reproduction for the rest of the female’s life.
17
Q

What is the concept of ovarian reserve?

A

As age increases from birth, the NGF population increases and begins to them decrease as age progresses until thwew is no longer a NGF population.

18
Q

How is external genitalia formed?

What does the genital tubercle begin to form in male and females (think genitals)?

A
  • Early in week 4 of development—in
    both sexes—the genital tubercle begins to
    enlarge to form the phallus.
    In males, the genital tubercle becomes the
    glans penis. The urogenital folds fuse to form
    the shaft of the penis. The labioscrotal
    swellings become the scrotum.
  • In females, the genital tubercle becomes the
    clitoris. The urogenital folds remain separate
    as the labia minora. The labioscrotal swellings
    become the labia majora where they remain
    unfused. Ventrally, the labioscrotal swellings
    fuse to form the mons pubis.
19
Q

What two physiological processes does puberty involve?

A
  • Gonadarche and Andrenarche
  • They produce gametes and sex steroids
  • Puberty and Gametogenesis
  • Gonadarche = the physical and
    functional maturation of the gonads, such that they produce gametes and sex steroids.
    – induced by increased production of the gonadotropic hormones follicle-
    stimulating hormone (FSH) and luteinizing hormone (LH) by the anterior pituitary.
    LH and FSH production by the anterior pituitary are under the control of gonadotropin-
    releasing hormone (GnRH), produced by neurons in the hypothalamus.
    = adrenarche, the increased production of the androgenic steroids by the adrenal
    cortex.

In males, gonadarche leads to the initiation of sperm production by the testes, and in
females it leads to folliculogenesis and menarche.

20
Q

What is the process of spermatogenesis?

A
  • Takes 64-72 days in humans
  • Mature sperm = 23 chromosomes (1N)
  • Gametogenesis= accomplished by meiosis

Key stages:

(i) Spermatocytogenesis - The generation of primary spermatocytes
- Mitotic division of spermatogonia
(ii) Spermatogenesis - Meiotic generation of round spermatids from spermatocytes
(iii) Spermiogenesis - Maturation of spermatid to spermatozoon
(iv) Spermiation - Release from Sertoli cell to tubule lumen

21
Q

What is the seminiferous tubule?

A
  • contains spermatognic cells and sertoli cells
  • Spermatogeic cells - stem cells ( Spermatocytes; Spermatids; Spermatoza (mature)) - always in contact with sertoli cells
  • Sertoli cells - support the development of the spermatids
  • Extend from the basement membrane to the lumen
  • Provide structural and metabolic support
  • Stimulated by FSH and testosterone
  • Promote cell division
22
Q

What is the role/function of Leydig (Interstitial cells)?

A
  • synthesis and secretion of testosterone in response to stimulation by LH
  • LH controls :
    • LH receptor availability (-ve feedback)
    • Leydig cell growth and differentiation
23
Q

What does testosterone produced by the Leydig cells do?

A
  • can act locally on the seminiferous tubules ro promote spermatogenesis
  • Can diffuse into the general circulation
24
Q

What is spermiogenesis (Cellular reorganisation)?

A
  • Transition from spermatid to spermatozoon
  • Sperm loose vast majority of their cytoplasm (taken up by sertoli cells)
  • centriole produces a flagellum
  • Golgi apparatus forms the acrosome vesicle
  • Gene machinery is shut down - becomes quiescent
  • Mitochondria migrate to the flagellum
25
Q

What are the 4 phases of spermatogenesis?

A
  • Spermatocytogenesis (proliferative) :Generation of primary spermatocytes and the replenishing of spermatogonial reserve
  • Spermatogenesis (Meiosis)
  • Meiotic generation of round spermatids from spermatocytes
  • Spermiogenesis ( Differentiation) - Maturation of spermatid into spermatozoon
  • Spermiation - Release of spermatozoon from sertoli cells
26
Q

What are the different stages of Meiosis in spermatogenesis?

A
  • Meiosis I — Primary Spermatocyte
  • Chromosomes replicate (from 2n to 4n)
  • Chromosomes condense and homologous pair
  • Chromosome crossover (chiasmata) — Genetic
    exchange
  • Homologous chromosomes separate
  • Longer period in this stage - N 24 days in men!
  • Meiosis Il — Secondary spermatocyte
  • Iry to 2ry spermatocytes (meiosis Il)
  • Chromosome do not replicate and remain
    condensed
  • Centromeres divide and separate chromatids
  • Generate haploid cells (In)
  • Short duration in men: hours!
27
Q

What is the hormonal control of spermatogenesis?

A
  • Secretion of LH and FSH from the anterior pituitary - stimylated by GNRH
  • LH acts on Leydig cells to regulate testosterone secretion (steroid hormones)
  • FSH acts on sertoli cells of the seminiferous tubules to enhance spermatogenesis
  • Feedback control regulates testicular function. Sertoli cells of the seminiferous tubules secrete inhibin (growth factor) which negatively regulates pituitary function
28
Q

What is Oogenesis and Folliculogenesis ?

A
  • Initiate during foetal life and run as
    parallel processes
  • Ooogenesis
  • Oocyte number determined at birth
  • Neo-oogenesis (mice, human, sheep?) —
  • Folliculogenesis
  • Oocytes within — arrested prophase I
  • Growth from primordial (activation) to
    pre-ovulatory allows maturational
    changes to improve meiotic and
    developmental competence
29
Q

What are the stages of follliculogenesis?

A
  • Takes 290 days for a recruited primordial follicle to grow to a fully- grown secondary follicle.
  • From cavitation or beginning antrum formation :
  • Takes 60 days to pass through the small , medium and large preovulatory Graafian follicle stages. Dominant follicle is then selected from a chohort of follicles. Once selected, 20 days are required for a dominant follicle too reach the ovulatory stage.