Lecture 1

Question 1

What are chromosomes?

What is a human karyotype?

Answer 1

Nuclear tiny structures containing a linear thread of DNA which transmit genetic information among other functions
Not normally visible but become visible during certain points in cell life

Human karyotype is full set of chromosomes in human
Single pair of sex chromosomes and 22 autosomes

Females have 2 X chromosomes and males have one X and one Y

Slides 1-2

Question 2

What is mitosis vs meiosis?

Answer 2

Mitosis- occurs in somatic cells for growth
Results in formation of 2 identical daughter cells with same number of chromosomes (46 in humans) and same DNA content as original cell

Meiosis- occurs in germ cells (spermatogonia in males and oogonia in females) for production of male and female gametes
Results in 4 haploid daughter cells
Continuum of 2 divisions in which homologous chromosomes separate during meiosis-1 and the chromatids separate during meiosis-2

Slides 3-7

Question 3

What’s the difference between meiosis in males (spermatogenesis) and meiosis in females (oogenesis)?

Answer 3

Males- one spermatogonium gives rise to 4 spermatids
Make meiosis gets halted from fertilization to puberty when FSH is produced and spermatogenesis finishes first cycle

Females- oogonium yields one mature oocyte and 2 polar bodies
Females meiosis depends on when they get pregnant, it starts when they become pregnant
Meiosis will never be completed in a females life if they don’t get pregnant

Slides 6-7

Question 4

How is the sex determined in offspring?

Answer 4

The genetic sex if a zygote is established at fertilization, when X or Y bearing sperm fertilizes an oocyte
The sex chromosomes from parents contribute to determining the genotypic sex
The genotypic sex determines the gonadal sex, which in turn determines the phenotypic sex that becomes fully established at puberty

Question 5

What are epigenetics?

Answer 5

An epigenetic modification isn’t a change in phenotype without a change in genotype
Cause cells with identical DNA to develop, appear, and function very different
Cellular characteristics heritable by daughter cells that don’t involve changes to underlying DNA sequence
DNA methylation and histone modification are involved
Environment, age, lifestyle, diseases can cause epigenetic changes

Slides 9-10

Question 6

What is DNA methylation?

Answer 6

Epigenetic mechanism
Methyl groups attach directly to DNA stands

Equilibrium between methylation and de-methylation directs healthy cell growth and differentiation
Imbalance in DNA methylation has been found in diseases like cancer

Question 7

What is the difference in gonadal sex changes for males and females?

Answer 7

Males- the testis develops from the medulla, while the cortex regresses
Y chronometer exerts powerful testis determining effect on the indifferent or developing gonad

Females- the ovary develops from the cortex, while the medulla regresses
In absence of Y chromosome, the indifferent gonad develops into an ovary

Slides 12-15

Question 8

How is the male sex established during embryogenesis?

Answer 8

The male sex is established when the primary sex chords differentiate into seminiferous tubules under the influence of the Y chromosome

Question 9

What is the testis determining gene? (TDF)

Answer 9

The testis determining factor (TDF) is a single gene located on the short arm of the Y chromosome
Also know as SRY (sex determining region Y)
TDF is necessary for testicular development
SRY gene triggers development of testis, which then makes androgens like testosterone and a glycoprotein like anti-Müllerian hormone necessary for male pattern of sex difference

Rarely TDF may be found translocated on other chromosomes (like in an XX male, whose sex chromosomes are XX but phenotype is male)

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Question 10

What is gonadal dysgenesis?

Answer 10

It is an abnormal gonadal differentiation

Ex: loss of one of the X chromosomes of the XX pair results in an individual with an XO sex chromosome constitution and ovarian dysgenesis

Ex: Turner syndrome, disorder of female sex characterized by short stature, primary amenorrhea, sexual infantilism, other congenital abnormalities

Slide 17

Question 11

What is the transformation of the genital ducts for males and females?

Answer 11

Males- the paramesonephric or Müllerian duct degenerates and the mesonephric or wolffian duct develops into the vas deferens, seminiferous tubules, and ejaculatory duct
This requires testosterone and anti-Müllerian hormone (AMH)

Females- mesonephric or wolffian duct degenerates and the paramesonephric or Müllerian ducts develops into the oviducts (Fallopian tubes), uterus, and upper third of the vagina

Slide 19-22

Question 12

What does absence of anti-Müllerian hormone (AMH) cause?

What produces AMH?

What about absence of testosterone?

Answer 12

Causes Müllerian ducts to develop in a female pattern

Sertoli cells produce AMH, shortly after, fetal leydig cells start to produce testosterone

Absence of testosterone causes the wolffian ducts to degenerate

Slide 22

Question 13

Is the ovary required for female duct development?

Answer 13

No, after bilateral removal of the ovaries, Müllerian development continues along normal female lines indicating that the ovary is not required for female duct development

Slide 23

Question 14

What does unilateral removal of the testis result in?

Answer 14

Unilateral removal of testis results in female duct (Müllerian) development in the same (ipsilateral) side as castration
The duct develops in a male pattern in the side with the remaining testis and virilization of the external genitalia proceeds normally

Slide 24

Question 15

What happens in the absence of both testes, while administering testosterone?

Answer 15

In the absence of both testes, administering testosterone preserves development of the wolffian ducts
However because of the absence of AMH, no Müllerian regression occurs

Slide 25

Question 16

What happens when you treat a female with testosterone?

Answer 16

In the presence of both ovaries, testosterone promotes development of the wolffian ducts
Without testes, no AMH is present and so the Müllerian ducts develop normally

Slide 26

Question 17

What are the 2 major roles that androgens (testosterone) play in sexual differentiation?

Answer 17

1. They trigger conversion of the wolffian ducts to the male ejaculatory system
2. They direct the differentiation of the urogenital sinus and external genitalia

Question 18

What phase of male sexual differentiation requires testosterone?
What phase requires conversion of testosterone to DHT?

Answer 18

The wolffian phase of male sex differentiation is regulated by testosterone

Virilization of the urogenital sinus, the prostate, penile urethra, and external genitalia during embryogenesis requires DHT, as does sexual maturation at puberty

Question 19

What is androgen binding protein (ABP)?

Answer 19

The Sertoli cells also produce ABP to bind and maintains a high concentration of testosterone locally for the stimulation of growth and differentiation of the wolffian ducts into the epididymis, the vas deferens, and the seminal vesicles, and the ejaculatory duct

Question 20

How is testosterone converted to DHT?

Answer 20

The cells of the external genitalia contain 5α-reductase and convert testosterone to DHT

The conversion of testosterone to DHT is required for normal male development of the external genitalia

Congenital absence of 5α-reductase is associated with normal development of the wolffian duct system but impaired virilization of the external genitalia

Question 21

How are adrenal steroids biosynthesized?

Answer 21

Pregnenolone -> aldosterone

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Question 22

What is congenital adrenal hyperplasia?

Answer 22

Ambiguous genitalia in genotypic females may result from disorders of adrenal function
Several forms of congenital adrenal hyperplasia have been described
Deficiencies in 21α-hydroxyl was, 11β-hydroxylase, and 3β-hydroxylsteroid hydrogenase all lead to virilization in females and thus ambiguous genitalia as a result of hypersecretion of adrenal androgens

Slides 34-36

Question 23

What is malepseudohermaphroditism?

Answer 23

Any defect in the mechanisms by which androgens act on target tissues in genotypic males may lead to a syndrome of male pseudo…
Affected ppl have normal male karyotype and unambiguous male gonads but ambiguous external genitalia or may phenotypically appear as females

Question 24

Which binds better to androgen receptor: dihydrotestosterone or testosterone?

Answer 24

DHT binds to the androgen receptor with an affinity that is about 100 fold greater than the binding of testosterone to androgen receptor

Question 25

How do steroid hormones work?

Answer 25

Steroid hormones enter target cell by simple diffusion across plasma membrane, bind with high affinity to receptors on cytosol or nucleus, this changes receptor conformation so that the active receptor-hormone complex now binds with high affinity to specific DNA sequences called steroid response elements (SREs), this stimulating transcription of appropriate genes

Slide 40

Question 26

What is endocrine, paracrine, and autocrine?

Answer 26

Endocrine- acts on distant tissues

Paracrine- acts on a neighbouring cell in same tissue

Autocrine- acts in the same cell that released the signalling molecule

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