Gamatogenesis

Embryology

* studies the prenatal development of gametes, fertilization, and development of embryos and fetuses

What does the human development process include (3)…

* gene regulation
* differentiation
* morphogenesis

Cellular events associated with developmental processes are (6)

* cell division
* cell migration
* cell rearrangement
* differentiation
* programmed cell death
* growth

Stages in ontogenetic development (5)

1. Gametogenesis
2. Fertilization
3. Cleavage
4. Morphogenesis

a. Cell and tissue differentiation

b. Pattern and polarity


5. Growth and maturation

Gametogenesis

* The formation of mature eggs and sperm (aka gametes)
* 1N = haploid

Fertilization

* Fusing of sperm and egg to for a zygote
* 2N = diploid

Cleavage

* Rapid mitotic cell division divisions of zygote (early embryo) to form the multicellular embryo (blastula)

Morphogenesis

* ‘genesis of shape’
* gastrulation and neurulation that form initial primary germ layers + organogenesis

Cell and Tissue Diifferentiation

* Cellular interactions that regulate gene activity and lead to specialized cell types

Pattern and Polarity

* The development of tissues and organs is a reflection of having symmetry

Growth and maturation

* The fetus grows as development continues, which persists throught the life process

The most critical stage of development occurs during the __ trimester

1st

PGC translates to

primordial germ cells

What are the 4 phases of gametogenesis

1. __origin__ outside the embryo of PGCs and their __migration__ to the gonads
2. increase in # of PGCs by __mitosis__
3. a reduction of chromosomal material by __meiosis__
4. Structural and functional __maturation__ of gametes (oogenesis, spermatogenesis)

Which phase of gametogenesis is identical in males and females

first phase

PGCs

* earliest recognizable precursors of gametes
* appears outside the gonads
* migrates to gonads during early embryonic development

PGCs are first recognizable how many days after fertilization

24 days

* set aside in the endodermal layer of the yolk sac (high glycogen and alkaline phosphatase content

Phase 1 : Origin of PGCs

* in the epiblast prior to gastrulation
* requires inductive signalling
* moved to a yolk sac where they’re determined
* PGCs re-enter the embryo and migrate to the developing gonads

Genital ridges

* The one way street where PGCs travel to develop into future gonads

Phase 1: The arduous journey (brief)

* b/w 4-6 weeks in the PGCs
* exit the yolk sac
* enter the hindgut epithelium
* migrate through the dorsal mesentery
* Til they reach the primordial of the gonads

How do PGCs migrate and know where to go?

1. Amoeboid (Amoeba crawl-like) movement during inital migration
2. Cytoplasmic processes link adjacent PGCs
3. Chemoattractants secreted by genital ridges
4. Migration by extending pseudopod (integral-fibronectin interactions)
5. Follow extracellular matrix “roadways lined with fibronectin

What are integrins important for?

PGC movement

Teratoma

* benign tumours/growth
* when PGC don’t reach where they’re supposed to go

What is a sacrococcygeal teratoma (SCT)

* unusual tumor in the newborn located at the base of the tailbone (coccyx)
* more common in females than males
* very large, but not malignant
* cured by surgery after birth

What are oropharyngeal teratomas

* Extremely rare
* associated with high neonatal mortality rate due to severe airway obstruction

Phase 2: Increase in the number of germ cells by mitosis

* after phase 1 they undergo a series of mitotic divisions
* PGC number increases exponentially to millions
* Oogonia: max # reached during gestation
* Spermatogonia: able to divide postnatally

Gender differences in germ cell mitosis - females

* oogonia undego an intense period(2nd to 5th month) of mitotic activity in embryonic ovary
* germ cell population 1000s → 7 mil
* Atresia of oogonia begins

Atresia

* the __degeneration__ of ovarian __follicles__ which do not __ovulate__ during the menstrual cycle

Gender differences in germ cell mitosis - males

* mitosis begins early in embryonic testes
* seminiferous tubules lined with germ cells
* beginning at puberty, subpopulations of spermatogonia undergo periodic waves of mitosis

Changes in the number of germ cells in the human ovary with increasing age

\

Phase 3: Reduction in chromosomal number by meiosis

* reduction of number of chromosome from diploid(2N) to haploid (1N)
* independent re-assortment -allows forr better mixing of genetic characteristics

Crossing-Over

* consist of the exchange of segments between the 2 chromosomes during the pachytene stage (3rd stage of the prophase of meiosis)
* occurs also in sex chromosome
* takes place in small region of homology b/w the X and Y chromosomes
* occurs at sites along the chromosomes → hotspots

Cohesin

* holds sister chromatids together during division

Condensin

* Is important in compaction of the chromosomes, necessary for mitotic and meiotic division

Compare mitosis and meiosis

Female Mature Gametes

oocyte or egg or ovum

Male Mature Gametes

Spermatozoon (sperm)

Oogenesis Overview

Female Reporductive System (Human) Diagram

Female Reporductive System Diagram

Structure of an Ovary

Ovarian Follicles (4)

* Basic unit of female reproductive biology
* contains a single oocyte
* initiated to grow and develop
* consists of granulosa cells and theca cells

What stimulates a gradual rise in the level of FSH in a primordial follicle

* A rise in GnRH
* Thus turning stimulates 5 to 20 primordial follicles to begin to develop

Folliculogenesis - Primordial Follicle step 1

* one cell thick: squamous
* cells from the ovary surround the arrested primary oocyte
* A rise in GnRH stimulates a gradual rise in the level of FSH.

Folliculogenesis - Primordial Follicle step 2

* one cell thick: cuboidal
* by birth, primary oocytes have a complete layer of follicular cells
* Zona pellucida begins to form but may not be visible

Folliculogenesis - Secondary Follicle step 1

* many cell layers; cuboidal
* Oocyte secretes active; stimulates granuloma cells to proliferate (cells secrete estrogen)
* Shortly after birth, follicular sells secrete a meiotic inhibitory factor (MIF)

What is Meiotic inhibitory factor (MIF)

* causes first meiotic arrest in diplotene of prophase I until puberty

Folliculogenesis - Secondary Follicle step 2

* FSH actis on granulosa cells; enhances active action
* Zona pellucida well developed
* Antrum visible
* Thea forming

Folliculogenesis - Mature Follicle

* many layers; cuboidal
* @ puberty, follicle enlarges
* Secondary oocyte arrested in Metaphase II until fertilization
* Antrumm very large
* Cumulus oophorus evident
* Corona radiata surrounds the mature secondary oocyte
* Thecal layers aare prominent

Luteinizing hormone (LH) surge results in

* MPF production
* Release from MI arrest
* Progesterone production

What is cumulus oophorus?

Surround oocyte in follicle and after ovulation

* Roles are: protection, development, during fertilization too

What is corona radiata?

Part of the cumulus oophorus; innermost layer closet to the ZP

What is zona pellucida

Surrounds secondary oocyte and polar body

* Roles are: binds spermatozoa, species-specific barriers

Folliculogenesis - Corpus luteum

* Ruptured and empty follicle (granulosa cells) left behind after ovulation
* Lutein reaction converts cells to progesterone-producing cells

Meiotic arrest involves second messengers and hormones: Arrest-

* ↑cAMP inactivates MPF
* meiosis arrested
* cGMP inhibits PDE3A

Meiotic resumption involves second messengers and hormones: Resumption of meiosis-

* LH surge
* closes gap junctions
* in effect decreases cAMP
* activates MPF

MPF stands for

maturation promoting factor

What is the theca

* cellular coverings from the surrounding ovarian storm begins to form around a __developing follicle__

Theca folliculi

* 2 or 3 layers thick
* differentiates into 2 layers: theca interna, and theca external

What is the theca interna

* inside granulosa cells
* highly vascularized and glandular

What is the theca externa

* outside granulosa cells
* connective tissue=like outer capsule

What are the major hormonal interaction in the theca and granulosa cells in follicle development (4)

* FSH
* Estrogen
* Activin
* Inhibin

What does FSH do? (3)

* Pituitary gonadotropin
* Acts on granulosa cells
* Stimulates estrogen production

What does Estrogen do?

* stimulate the formation of LH receptors on granulosa cells

What does activin do?

* Stimulates granulosa cells proliferation (rapid reproduction of a cell)

What does Inhibin do?

* secreted by granulosa cells of dominant secondary follicle
* inhibits secretion of FSH (and LH) by negative feedback
* Results in atresia of other follicles

What are the 3 stages of the menstral cycle?

* Proliferative Phase (day 5 - 14)
* Ovulation
* Secretary Phase (day 14 - 28)

What happens during the proliferative phase

* GnRH stimulates the release of FSH and LH
* secondary follicles secrete estrogen (acts of reproductive tract)
* LH and FSH surge

What happens during ovulation?

* Result of LH surge
* Transforms ruptured follicle to corpus luteum (secretes progesterone)

What happens during the secretory phase?

* Progesterone helps ready the repro tract for implantation
* Inhibin production
* Endometrium sheds

3 stages of oogenesis

* oocytogenesis (oogonia developing into primary oocytes by mitosis)
* ootidogenesis (the primary oocyte turns into an secondary oocyte)
* oogenesis (formation of female gametes)

What is ooctyogenesis?

* oogonia developing into primary oocytes by mitosis
* complete either before or after birth
* primary oocytes reach their maximum development at roughly 20 weeks of gestational age
* primary oocytes at birth are approximately 1-2 million

What is ootidogenesis

* primary oocyte develops into a secondary oocyte
* It begins at prenatal age, stops in the diplotene \n stage of prophase I of the first meiotic division (dictyate) \n until puberty.
* At puberty, some primary oocytes develop in each \n menstrual cycle, chromosomal crossover occurs, \n meiosis I is completed, first polar body extruded and \n oocyte secondary oocyte

What is oogenesis?

* the haploid secondary oocyte initiates meiosis II and stops at the metaphase II stage until fertilization

Hormonal control of oogenesis/folliculogenesis

* estrogen and progesterone can be either a negative and positive regulator

What is oocyte cytoplasmic maturation?

* the accumulation of mRNA, proteins, substrates, and nutrients required to achieve the oocyte developmental competence that fosters embryonic developmental competence

Parts of oocyte cytoplasmic maturation

* Mitochondria → redistribution
* Golgi apparatus → fragmentation
* Endoplasmic reticulum → redistribution and structural changes
* Cytoskeleton→ reorganization

Spermatogenesis

* process in which spermatozoa are produced from male primordial germ cells by way of mitosis and meiosis

Mature Spermatozoon

Male Reproductive Tract

Male Reproductive

What are the 4 stages of spermatogenesis

* spermatocytogenesis
* spermatidogenesis
* Spermiogenesis
* Spermiation

What is spermatocytogenesis?

from spermatogonium to primary spermatocyte and then secondary spermatocyte

Spermatogonial Phase

* Type A dark (Ad) spermatogonia: stem cells of the seminiferous epithelium
* Type A pale (Ap) spermatogonia: commited to differentiation
* Type B spermatogonia: differentiated from type A

What is the spermatogonial Phase

* Type A(d) cells, with dark nuclei. These cells replicate to \n ensure a constant supply of spermatogonia
* Type A(p) cells, with pale nuclei. These cells divide by mitosis to produce Type B cells.
* Type B cells, which divide to give rise to primary \n spermatocytes.

Second Phase of Spermatocytogenesis

* each primary diploid spermatocyte duplicates its DNA and divide in 2 haploid secondary spermatocytes by meiosis 1

What is spermatidogensis?

* the creation of spermatids from secondary \n spermatocytes. Secondary spermatocytes \n produced earlier rapidly enter meiosis II and divide \n to produce haploid spermatids.

What is spermiogenesis?

* spermatids form a tail by growing microtubules on one of the centrioles (basal body)
* microtubules = axoneme.
* anterior part of the tail (called midpiece) thickens because mitochondria are arranged around → energy supply.
* DNA undergoes packaging → highly condensed.
* tightly packed chromatin is transcriptionally inactive.
* Golgi apparatus surrounds the condensed nucleus → \n acrosome.
* testosterone removes the remaining extra \n (residual bodies) and organelles.
* residual bodies are phagocytosed by Sertoli cells. \n cytoplasm \n MATURE SPERMATOZOA, but NOT MOTILE

Spermiation

* The release of the mature spermatozoa from the sertoli cells into the lumen of the seminiferous tubule

Sertoli cells

* Provide structural and metabolic support to the developing sperm cells
* A single Sertoli cell extends from the basement membrane to the lumen of the seminiferous tubule

Hormonal Control of Spermatogenesis

* spermatogenesis occurs at puberty due to the interaction of the hypothalamus, pituitary gland and Leydig cells.
* FSH stimulates both the production of ABP by Sertoli \n cells, and the formation of the blood-testis barrier.
* inhibin acts to decrease the levels of FSH.
* The Sertoli cells themselves mediate parts of spermatogenesis producing the hormones estradiol and \n inhibin.

How does sperm transport in the male?

* transported by testicular fluid from the seminiferous tubules to the head(capus) of the epididymis


* 4-12 days in the epididymal duct → biochemical maturation
* On ejaculation, the spermatozoa pass through ductus \n deferens and mix with secretion from the **seminal vesicles** (fructose and prostaglandins) and **prostate glands** (citric acid, acid phosphatase, zinc and magnesium ions

What is hypospermia

* production of not enough sperm

Follicular rupture into peritoneal cavity near…?

Frimbriae (Infundibulum) of the oviduct

Ciliated epithelial cells and \n the activity of the smooth \n muscle of the oviduct actively \n funnel the ovum into the \n oviduct to the region of

ampulla

Fertilization occurs at

ampulla or ampulla/isthmus junction

How long does tubal transport in humans take

* 3-4 days

How long does slow transport take in the ampulla

approx. 72hrs

How long does rapid phase through the isthmus and into the uterus

approx. 8hrs

What hormone is necessary for egg to pass the uterotubal junction

* progesterone