Lecture 3

Gametogenesis

generation of gametes

Sex determination

dependent on X and Y chromosomes, informs how gametes form

Genital ridge

bipotential, can become ovary or testes depending on genotype

Female

default pathway without any genetic input

Wnt4

signalling molecule active in genital ridge when XX; promotes B-catenin

B-catenin

transcription factor promoted by Wnt4, promotes expression of ovary-forming genes by binding to enhancers

Sox9 loss of function

XY but female gonads

Testis and ovary

structures set aside early

Sry

male determining gene on the Y chromosome

Sox9

turns on if Sry present during critical period; downstream of Sry and autosomal; turns on testis-forming genes

Fgf9

needed by Sox9 to stay active

Cross-repression

Sox9 and B-catenin negatively regulate each other

Mapping of Sry

occurred by analyzing DNA of XX men and Xy women

Primordial germ cell migration

identical in both males and females; stem cells divide during this process

Germ cells

bipotential until they reach the gonad where they can become either eggs or sperm

Gonad environment

determines whether PGCs develop as sperm or eggs

Hindgut

where PGCs originate

Dorsal mesentery

where PGCs travel through to reach the gonad

Teratomas

if PGCs get lost in migration, they end up in wrong place; not terminal cancer; heterogenous (can have teeth, hair, etc.)

Teratomas outside of baby

can remove tumour and baby will be fine Teratomas if in a difficult place

Spermatogenesis

begins at puberty; can generate >1000 sperm per second; occurs fully in testes

1 - mitotic proliferation

spermatogonia

2 - meiotic division

spermatocytes

3 - differentiation

spermatids

Meiosis

produces 4 haploid daughters with only mom or dad's DNA

Mitosis

produces 2 diploid daughters

Seminiferous tubules

where sperm develop (begins on the outside, progresses to the middle)

Uncommitted cells

found at periphery of tube

Type A Spermatogonia

primordial germ cells mitotically dividing and increasing number of cells

Primary spermatocyte

undergoes meiosis to form secondary spermatocyte

Secondary spermatocyte

undergo secondary meiotic division to form spermatids

Spermatids

differentiate into sperm

Sperm

swim away (lumen has fluid)

Sertoli cells

absorb residual bodies that developing sperm has removed in order to become aerodynamic; provide protection; autosomal non germ cells

Closer to lumen

Terminal spermatogonia

replicate DNA then transition into primary spermatocytes

Spermatozoa

fully mature sperm

2n with 4 chromosomes

Spermatogonium ploidy

2n 4c

Primary spermatocyte ploidy

2n to 1n

first meiotic division

1n 2c

secondary spermatocyte ploidy

2c to 1c

second meiotic division

1n 1c

Spermatid ploidy

1n 1c

spermatozoa ploidy

Spermiogenesis

differentiation of sperm

Nuclear Shaping and Condensation

Changes in chromatin packaging from somatic histones to sperm-specific protamines (ensures compactness)

Formation of Flagellum

Elongation of microtubules from the centriole at the base of the nucleus

Formation of Acrosome

(from the Golgi) at the front end of the sperm

Acrosome

full of enzymes needed to get to final steps of fertilization; cut through protection of egg to allow it to reach egg

Rearrangement of Organelles

Mitochondria form a ring at the base of the flagellum to act as a motor to power flagellum

Shedding of the Residual Body

Most of the cytoplasm is absorbed by the Sertoli cells

Immunohistochemistry

can be used to identify the sperm cell's structure

Nuclear protein

sperm cell 1st protein that binds to DNA

64 days

each cycle of spermatogenesis

16 days

spermatogonial mitosis

24 days

first meiotic division

Few hours

second meiotic division

24 days

spermiogenesis

100 million

sperm made in one testicle everyday

200 million

sperm in one ejaculation

Unused sperm

reabsorbed or passed out through urine

10^13

sperm produced by human male in lifetime

Oogonium

mitotically dividing cells, increase pool of eggs

Primary oocyte

goes through meiotic division to form secondary oocyte

Secondary oocyte

divides to eventually make egg

Polar bodies

daughters of meiotic division that don’t become eggs; same DNA but less cytoplasm and no organelles

Second meiotic division

makes a fertilized egg and tiny polar body

Early mitotic proliferation

only reserved at early fetal periods of future female

Puberty

eggs are no longer frozen, many stay frozen until some are allowed to be relieved and enter the process of meiotic division

Eggs that aren't fertilized

do not complete meiosis 2

2-3

number of polar bodies, depending on whether first one divides

Role of polar bodies

none known other than to reduce genetic complement of the egg with minimal reduction in cytoplasm

Die off or reabsorbed by egg/embryo

fate of polar bodies

Ovary

oocyte to meiosis 2 ruptures from here and awaits sperm/dies

Oogonia

Between the 2nd and 5th month of pregnancy, their number increases from a few thousand to 7 million, representing the maximum number of germ cells ever found in the ovaries.

Atresia

continuous process throughout female life; crash in number of oogonia

Primordial germ

cells become mitotic cells to amplify the pool of progenitors to create gametes

1/3

conceptions abort spontaneously due to NDJ resulting in chromosomal abnormality

1/4

abortions occur prior to the detection of pregnancy

Chromosomal abnormalities

40-50% of spontaneous abortions

Developmental abnormalities

fetuses that survive to term despite having genetic abnormalities

Non disjunction

chromosomal abnormality causing embryo to be unable to get through first few cleavages and abort before the woman knows she's pregnant; have missing or extra chromosomes or duplicated/deleted/rearranged segments

Monosomy

absence of a chromosome in a gamete

Trisomy

presence of two of the same chromosomes in a gamete

Down syndrome

trisomy 21

Turner syndrome

XO female, one gamete not carrying sex chromosome

Female body

final changes occur to sperm