Genetics of Sex Determination

Question 1

Give a brief outline of gametogenesis

Answer 1

Gametogenesis is the development of eggs (ova) or sperm from primordial germ cells that originate in the endoderm of the yolk sac at the 4th week of embryonic life. During the 6th week, they migrate to the genital ridge and associate with somatic cells to form the primitive gonad. Gonads then differentiates into ovary or testes in accordance to sex-determining genetic guidance

Question 2

What is the SRY?

Answer 2

This is the sex determining region found on the Y chromosome, whose presence indicates that indifferent gonads will become testes

NOTE: In the absence of SRY, indifferent goands default to ovary (kind of)

Question 3

What do the leydig and sertoli cells produce in the presence of SRY?

Answer 3

• Sertoli Cells produce Anti-Mullerian Inhibiting Hormone (AMH)
• Leydig cells produce Testosterone

SALT

Question 4

Describe how spermatogenesis occurs

Answer 4

Prior to puberty, Spermatogonia (2N) develop into primary spermatocytes (2N) via mitosis and line the periphery of the seminiferous tubules under the care of Sertoli cells. The onset of sexual maturity (testosterone driven) drives:

• Meiosis 1 division into 2 secondary spermatocytes (N)
• Meiosis II division into 2 spermatids (N) because homologues separate
• Spermatids (N) then develop into mature sperm and are stored in the epididymis

Question 5

What is Capacitation?

Answer 5

Capacitation involves the destabilisation of the acrosomal sperm head membrane allowing greater binding between sperm and oocyte. This change is facilitated by the removal of sterols (e.g. cholesterol) and non-covalently bound epididymal/seminal glycoproteins. The result is a more fluid membrane with an increased permeability to Ca2+.

An influx of Ca2+ produces increased intracellular cAMP levels and thus, an increase in motility. Hyperactivation coincides with the onset of capacitation and is the result of the increased Ca2+ levels. The tripeptide FPP (fertilization promoting peptide) produced by the male is essential for capacitation (high levels of FPP prevent capacitation, the proper concentration occurs after ejaculation in the female reproductive tract where the concentration drops after mixing with vaginal secretions and/or becomes less active due to the pH of the vagina). It has a synergistic stimulatory effect with adenosine that increases adenylyl cyclase activity in the sperm. FPP is found in the seminal fluid (FPP produced in prostate gland), and comes into contact with the spermatozoa upon ejaculation.

In vivo this step typically occurs after ejaculation, in the female reproductive tract.

Question 6

How long does spermatogenesis take?

Answer 6

64 days (•200 million sperm per ejaculate)

Question 7

What is a major difference in the timing of spermatogenesis and oogenesis in life?

Answer 7

spermatogenesis is constantly occurring throughout life from puberty while oogenesis is largely complete by birth

Question 8

How many oocytes are typically available at birth?

Answer 8

2.5 million (via 30 mitoses)- MOST degenerate so there are only 400 mature eggs that are candidates for ovulation/reproduction

Question 9

Describe oogenesis

Answer 9

• Oogonia in the female embryo begin Meiosis I during month 3 of embryologic prenatal development and are arrested in the primary oocyte at Dictyotene of Prophase I by birth
• Meiosis I is completed at ovulation to produce a secondary oocyte and a polar body
• Meiosis II is completed at fertilization to produce a ootid and another polar body

Question 10

What phase of the cell cycle does DNA replication occur?

Answer 10

Interphase. This occurs before meiosis!!

Each chromosome goes from univalent to a bivalent unit with identical sister chromatids joined by a centromere

Question 11

What are the stages of meiosis?

Answer 11

• Prophase
• Metaphase
• Anaphase
• Telophase

Question 12

What are the stages of prophase?

Answer 12

• Leptotene
• Zygotene
• Pachytene
• Diplotene
• Diakinesis

Question 13

What happens in leptotene?

Answer 13

chromosomes have already replicated following interphase, but lie on top of each other

Question 14

What happens in zygotene?

Answer 14

homologous pairs move together and pair/synapse and shorten

Question 15

What happens in pachytene?

Answer 15

This is the first time you can see the bivalent chromosome (cheerleader pose). The 2 homologous chromosomes now look like a tetrad

Question 16

What happens in diplotene during meiosis I?

Answer 16

cross-over. Crossing over occurs (on average) on one arm of each chromosome

Crossing-over multiplies the already huge number of different gamete types produced by independent assortment.

Question 17

What happens in diakinesis?

Answer 17

chromosome coil and continue to shorten and oogenesis is frozen here until ovulation

Question 18

What events occur during metaphase?

Answer 18

• Nuclear membrane disappears
• Spindle appears
• Pairs align on metaphase plate

Again, remember that primary oocytes are arrested in prophase of meiosis until ovulation, at which time they fully complete meiosis I, with anaphase and telophase following the completion of metaphase I

Question 19

Which occurs more quickly, meiosis I or II?

Answer 19

II.

Question 20

Remember that in meiosis II, DNA replication does NOT occur

Answer 20

Answer 21

Question 22

Question 23

What happens to the Mesonephric and Mullerian Ducts if AMH is present?

Answer 23

Testosterone helps allow the Mesonephric ducts (Wolffian ducts) to persist and eventually differentiate into the epidydimis, vas deferens, seminal vesicles, while AMH production from Sertoli cells causes regression of Mullerian ducts (which would have formed the female genital tract)

Question 24

What is Insl3?

Answer 24

insulin-like substance 3; produced by the gonad, may play a role testicular descent