Gametogenesis
 Generating the sex cells.
 Oogenesis and folliculogenesis in the ovary
 Spermatogenesis in the seminiferous tubules of the testes.
 Amniotes (birds, reptiles, mammals):
 Series of changes or processes where the germplasm (specialized
generative cells) → PGCs (Primordial Germ Cells) → Specialized
sex cells (gametes)
 Germplasm – not obvious in mammals; distinguishing structure of
germ cells. It is a cell-dense association of mRNAs and mRNA-
binding proteins such as VASA, DAZL, and MILI homologues.
Phases of Gametogenesis
1. Generation of germ cells and migration to the gonads.
2. Multiplication of germ cells in the gonads (mitosis).
3. Reduction in the number of chromosomes by half (meiosis).
4. Maturation and differentiation.
Phase 1: The germ cells and their origin
 Arise outside the gonads.
 Recognizable at early stage of development.
- Anuran amphibians:
- PGCs identified in the yolk sac endoderm.
o PGCs
- Large size; high content of alkaline phosphatase.
- Recognizable in humans 24d post fertilization in the yolk
sac endodermal layer.
o In mouse or rodents
 Hahnel and Eddy (1986) – PGCs originally reside in the
epiblast (ectodermal origin) of gastrula.
 Ginsburg (1990) – localized the region in the ExEmbryo.
Mesoderm posterior to the primitive streak in a 7.25th
day embryo.
- Development of PGCs depend on signals.
- Radical expression of pluripotency markers
 Oct-4+
 NANOG
 SOX2 genes.
o Bone Morphogenetic Protein (BMP) signaling – transformation
growth factor 𝛽-superfamily; Needed for the induction of the
initial cluster of PGC precursors in the proximal-posterior
epiblast at 6.25-7 ED embryos.
From the epiblast, the PGCs move out
to the yolk sac where they get
specified.
Induction of Murine Primordial Germ Cells
A) AtE6.25, a small population of PGC precursors (green) is induced at
the border between extraembryonic (red) and embryonic(orange)
ectoderm. BMPs are responsible for this induction.
(B) Between E6.5 and E7.0, the number of PGC precursors increases.
Still unknown signals from the visceral endoderm may help regulate
the size
of the founding population.
(C)At E7.25, the founding population of the PGCs (740 cells) is present
at the base of the allantois and the PGCs migrate into the(visceral)
endoderm. Signals from the surrounding tissues maybe involved in
PGC specification,
(D)Sagittal section of a E7.5 chimeric mouse embryo produced by
injection of wild type mouse ES cells into a host ROSA26 blastocyst
(ubiquitously expressing X-gal). The ES contributed to about 100% of
the embryonic tissues including the PGCs (red-positive for alkaline
phosphatase activity). The PGCs are visible at the posterior side of the
embryo (right) at the base of the allantois. The tissues derived from
the host ROSA26 blastocyst (blue-positive for LacZ) are the primitive
endoderm-derived visceral endoderm and the throphectoderm-
derived extraembryonic ectoderm. Note the PGCs initiating the
migratory journey intercalating in the host-derived endoderm.
The Life Cycle of Murine Germ Cells
After fertilization, the zygote starts cleaving forming a 2-cell embryo
that continues cleaving giving rise to the blastocyst (middle row). The
blastocyst consists of the trophectoderm (green), the primitive
endoderm (yellow) and the inner cell mass (orange). After
implantation, the inner cell mass/epiblast (orange) undergoes
cavitation and epithelializes. During gastrulation, a new germ layer is
formed, the mesoderm (blue). The primordial germ cells (PGCs) are
specified at E7.25 (black arrow) at the base of the mesodermal
allantois. Thereafter, the PGCs migrate through the forming hindgut
and the dorsal mesenterium to finally lodge in the genital ridges.
Upon sex determination, female (oogonia) and male (spermatogonia)
germ cells follow different fates. In the ovary (top row), the oocytes
mature in their follicles and are then released during ovulation. In the
testis (bottom row), spermatogenesis takes place to generate motile
sperm cells able to fertilize a mature oocyte.
 Third week: Primordial Germ Cells
wander in an amoeboid manner
from the primary ectoderm into the
yolk sac wall and collect near the
exit of the allantois. They are
extraembryonal, lying in the
endoderm and mesoderm of the
yolk sac wall. Having emigrated
from the ectoderm, the PGCs are
now among the endoderm cells in
the secondary yolk sac wall.
Teratoma
 Bizarre tumor when PGC stays in the hindgut or goes to the
foregut.
 Chemoattractant not functioning well.
Phase 2: Proliferation of Germ Cells (mitosis)
 PGCs to oogonia or spermatogonia.
 Mitotic patterns in the gonads differ wildy between males and
females.

Route of Mammalian PGC Migration

1. After collecting at the allantois (by day 7.5), the PGCs migrate
to the adjacent yolk sac. By this time, they have already split
into two populations that will migrate to either the right or
the left genital ridge.
2. The PGCs then move caudally from the yolk sac through the
newly formed hindgut and up the dorsal mesentery into the
genital ridge.
3. Most of the PGCs have reached the developing mouse gonad
by the 11th day after fertilization. During this trek, they have
proliferated from an initial population of 10-100 cells to the
2500-5000 PGCs present in the gonads by day 12.

Proposed Migratory Pathway Phase 3: Reduction in chromosome number by half (Meiosis)

 Spermatogenesis
 PGCs become spermatozoa through mitotic multiplication,
meiosis and spermiogenesis.
 It occurs throughout life.
 Pathway:
1. PGCs at the genital ridge
2. Sex cords
3. Seminiferous tubules
4. Tubular epithelium
5. Sertoli cells – no distinct nucleus; secrete androgen-binding
protein; serve as blood- testes barrier; degrade the residual
cytoplasmic ridges that connect spermatogenic cells.
 Stem cells – capable of self-renewal. Fates:
o Another round of self-renewal (mitosis)
Chromosomes prone to nondisjunction: o Death
21, 15, 18, and 13 o Another round of growth and becomes a primary
spermatocyte.
 Type B spermatogonia – last to undergo mitosis.
 Spermatids – undergo spermeiogenesis.  Differ among vertebrates depending on type of fertilization
o Cytoplasmic bridges – make sure that spermatids will (internal or external).
mature in sync.
 Categories of changes BMP8B (bone morphogenetic protein 8B)
o Recognization of the cytoplasm  Synthesized by spermatogonia.
 Golgi apparatus  Regulates the initiation of spermatogenesis during puberty.
 Centrioles
 Mitochondria Oogenesis
o Progressive reduction in nuclear size  PGCs undergo cellular, molecular, and physiological phenomena
 Nuclear elongation to become mature oocytes.
 Loss of water  Primary oocyte undergoes arrested stages.
 Elimination of RNA; leaving only DNA  Unequal cytoplasmic divisions during meiotic divisions.
 Only one functional oocyte produced per cycle; polar bodies
Major Stages in Spermiogenesis produced.

 Acrosome cup – formed by golgi apparatus. It contains

hyaluronidase to penetrate egg.

Sperm Maturation
Human Oogenesis and Follicular Development Summary
MALE FEMALE
MITOSIS continuous stops early before
throughout life birth
MEIOSIS starts late during starts early before
puberty birth but gets
arrested at Prophase
I, Diplotene
CYTOPLASMIC equal unequal
DIVISION
PB - +
NUMBER OF CELLS 4 1
PRODUCED

Hormonal Control of Oocyte Maturation