Presentation explaining the process of meiosis in humans and the meiotic arrest of oocyte anf its significance

1. CELL DIVISION
MEIOSIS
SABHYATACHOUBEY

2. Contents
1. HISTORY
2. UNDERSTANDING MEIOSIS
3. MEIOSIS I AND II
4. MEIOTIC ARREST IN OOCYTE
5. CURRENT RESEARCH

3. HISTORY
● First discovered and described by Oscar Hertwig in
echinoderm eggs. (1876)
● Described again by Van Benden in roundworm egg. (1883)
● August Weismann described the significance of meiosis for
copy and inheritance. (1890)
● T.H. Morgan detected crossovers in meiosis within
drosophila- genetic traits are transmitted on chromosomes.
(1911)
Edouard Van Benden
(1846-1910)

4. WHAT IS MEIOSIS?
• Term meiosis- derived from Greek word “meioun”- to diminish.
• Term coined by J.B. Farmer and J.E.S. Moore.
• Meiosis occurs in germ cells of all living organisms.
• Responsible for formation of gametes (spermatogenesis and oogenesis).
• Original cell- diploid (2n)
• Four daughter cells produced- haploid (n)
• Two successive nuclear divisions.

5. WHAT IS MEIOSIS?
• Meiosis divided into two stages-
1. Meiosis I (reductional division)
2. Meiosis II (equational division)
• 4 daughter cells formed at the end of
meiosis
• Each daughter cell have half the number
of chromosomes as the parent cell.

6. MEIOSIS I
01

7. MEIOSIS I
• Before a dividing cell enters meiosis, it is in a growth period
called Interphase.
• The interphase just before the entry of cell in meiosis is meiotic
interphase.
• Interphase-
1. G1 phase- cell growth
2. S phase- replication of DNA, centrosomes
3. G2 phase- final preparation
• In S phase, each chromosome is replicated to form two identical
copies, called sister chromatids- held together at the
centromere by cohesin proteins.
• Cohesin holds the chromatids together until anaphase II.

8. Events in meiosis I-
1. homologous chromosomes pair up
2. exchange genetic material through crossing over
3. Separation of homologous chromosomes
4. Formation of two haploid daughter cells
Four stages of meiosis I-
1. Prophase I
2. Metaphase I
3. Anaphase I
4. Telophase I
• Prophase I is the longest in duration compared to prophase in mitosis.
• Takes about 85-95% of total time for meiosis.
• 5 stages-
1.Leptotene 2.Zygotene 3.Pachytene 4.Diplotene 5.Diakinesis

9. PROPHASE I
1. Leptonema (Greek- threads)
2. Condensation of chromosomes starts
3. Increase in nuclear volume
4. chromosomes ends attached to inner
nuclear envelope
5. Bouquet stage- facilitates homologous
chromosomes pairing and synapsis
LEPTOTENE

10. 1. Zygonema (Greek- paired threads)
2. Synapsis- pairing of homologous chromosomes
3. Homologous chromosomes- pair of chromosomes with
same gene sequence, loci, chromosomal length and
centromere location.
4. Bivalent (Tetrad)- pair of homologous chromosomes
5. Formation of Synaptonemal complex- protein structure
formed between two homologous chromosomes.
• Tripartite structure (three layers)-
• Two lateral elements: These run along each
homologous chromosome, like rails on a railroad track.
• Central element: This joins the lateral elements in the
middle, creating a zipper-like connection.
• Three main proteins, SYCP1, SYCP2, and SYCP3, make
up the bulk of the SC.
ZYGOTENE

11. Functions of SC-
1. Synapsis and alignment
2. Crossing over
3. Checkpoint control: The SC acts as a checkpoint, ensuring that all chromosomes are
properly paired and crossing over has happened before proceeding to the next stage of
meiosis.

12. 1. Pachynema
2. Process of synapsis is complete.
3. Formation of recombination nodules at synaptonemal
complex- site of crossing over.
4. Crossing over- Exchange of genetic material between
non-sister chromatids of homologous chromosomes.
5. EXCEPTION- NO CROSSING OVER IN DROSOPHILA
AND FEMALE SILKWORM, MAY OCCUR IN SOMATIC
CELLS (REPORTED BY STERN)
6. Hot spots- region of high crossing over frequencies
7. Cold spots- region of low crossing over frequencies
PACHYTENE

13. 1. Diplonema
2. Desynapsis begins- dissolution of synaptonemal
complex
3. Chiasmata is formed (‘X’ shaped structure
representing site of crossing over)
4. Recombination completes
5. Diplotene is arrested in human oocytes and lasts
for years (birth till puberty).
DIPLOTENE

14. 1. Condensation of chromosomes completes
2. Nucleolus and nuclear envelope disappear toward
the end of this stage
3. Spindle apparatus becomes organized (spindle
microtubules+centrosomes+kinetochores)
4. Centrioles migrate away from each other
DIAKINESIS

16. MEIOTIC SPINDLES
Composed of 2 types of microtubules-
1. Kinetochore MT- attaches to kinetochores,
helps in movement and segregation
2. Non-kinetochore MT- overlap in spindle’s
midzone and push the spindle poles apart
3 types of non-kinetochore MTs
1. Astral
2. Polar
3. Overlap
METAPHASE I

17. 1. Movement of bivalents to metaphase plate
2. Attachment of kinetochore MTs to bivalent
3. Centrioles at opposite poles
METAPHASE I

18. 1. Separation of homologous chromosomes (unlike
mitosis where sister chromatids are separated).
2. Meiosis specific cohesion- Rec8 inhibits the
separation of sister chromatids.
3. Reduction in number of chromosomes from 2n to
n.
ANAPHASE I

19. 1. Migration of homologous chromosomes towards
opposite poles completes.
2. Nuclear envelope is reformed around the two
separated groups of chromosomes.
3. Nucleolus reappears.
TELOPHASE I

20. 1. Cytokinesis involves formation of cleavage
furrow, resulting in the formation of two daughter
cells.
2. Daughter cells have haploid set if chromosomes.
3. Time gap between meiosis I and II is
interkinesis.
4. Short or may not occur.
5. No DNA replication.
CYTOKINESES and INTERKINESIS

21. MEIOSIS II
02

22. Meiosis II is similar to mitosis, except the absence of S phase.
1. Prophase II-
● The cells have one chromosome from each homologous pair.
● Disappearance of nucleoli and nuclear envelope.
● Condensation of chromosomes.
● Centrosomes move to the polar regions.
2. Metaphase II-
● Chromosomes align at the metaphase plate.
● Attachment of spindle fibers to kinetochore.
● The new equatorial metaphase plate is rotated by 90 degrees when compared to meiosis I, perpendicular to the
previous plate.
3. Anaphase II-
● Centromeres divide and the sister chromatids are pulled to opposite poles.
4. Telophase II-
● Spindle disappears, nuclei form, and cytokinesis takes place.
● Disassembly of the spindle.
● Nuclear envelopes reform and cleavage produces four daughter cells, each with a haploid set of chromosomes.
MEIOSIS II

24. Each chromosome has just
one chromatid

25.  Meiotic arrest in oocyte is a highly specialized process.
 In humans, oocytes are arrested first at diplotene stage of prophase I from fetal stage till puberty and later at
metaphase II stage .
1. Initiation of Meiosis:
 Oocyte begins meiosis during fetal development.
2. Arrest at Prophase I:
 Oocyte arrested at diplotene stage of prophase I until sexual maturity.
3. Maintenance of Meiotic Arrest:
 High levels of cAMP within oocyte maintain meiotic arrest.
 cAMP inhibits the activity of maturation-promoting factor (MPF), a complex of cyclin B and CDK I
that drives the progression of the cell cycle.
 Adenylyl cyclase (AC) produces cAMP.
 Gs protein stimulates AC activity.
 G protein-coupled receptor 3 (GPR3) activates Gs protein.
 Inhibition of AC3 or Gs protein leads to spontaneous meiotic resumption.
4. Role of PDE3 in cAMP Degradation:
1. Phosphodiesterase 3 (PDE3) degrades Camp, preventing spontaneous meiotic maturation.
1. Inhibition of PDE3 elevates cAMP levels, maintaining arrest.
MEIOTIC ARREST IN OCCYTE

26. MEIOTIC ARREST IN OCCYTE
5. NPPC/NPR2 System in Granulosa Cells:
 cGMP produced in granulosa cells via NPPC/NPR2 system.
 cGMP transported to oocyte, sustaining high cAMP levels.
 Follicle-stimulating hormone (FSH) sustains NPPC/NPR2 expression in granulosa cells.
6. Regulation by LH Surge:
 LH surge downregulates NPPC/NPR2 (natriuretic peptide precursor C and guanylyl cyclase receptor 2) system in
granulosa cells.
 Reduced cGMP levels in oocyte lead to meiotic resumption.
 Reduced cGMP releases PDE3 from inhibition, degrading cAMP and activating maturation promoting factor
(MPF).
7. Resumption of Meiosis:
 MPF activation induces resumption of meiosis.
 Chromosomes condense, nuclear envelope breaks down, and spindle formation occurs.
 Meiosis progresses through metaphase I, anaphase I, telophase I, and cytokinesis.
 Meiosis II initiated after ovulation and completion of meiosis I.
 At metaphase II, the oocyte becomes arrested again, awaiting fertilization.
 Oocyte becomes haploid after second meiotic division. (primary to secondary oocyte)
8. Fertilization and Embryo Development:
1. If fertilized, the secondary oocyte completes meiosis II, yielding a mature egg and a second polar body.
2. If fertilization does not occur, the egg is not fertilized, and it eventually degenerates.

27.  While in the arrest stage, the oocyte remains suspended in prophase I of meiosis, characterized by the presence
of a germinal vesicle (nucleus). During this time, the oocyte undergoes essential processes such as DNA
replication, chromosome pairing, and recombination. Additionally, the oocyte accumulates maternal
mRNA and proteins necessary for subsequent stages of development.
WHAT HAPPENS TO OOCYTE IN FIRST
MEIOTIC ARREST?

29. CURRENT RESEARCHES
1. Meiotic Control and Regulation:
● Establishing and maintaining fertility: the importance of cell cycle arrest: This study
demonstrates the crucial role of CDK inhibitors (p21, p27) in initiating and regulating meiotic arrest
through interaction with kinases CDK2 and CDK4/6. It identifies MEIOSIN as a cofactor of
STRA8, facilitating transcriptional activation during meiotic entry. Additionally, ZGLP1 is shown to be
indispensable for PGC differentiation and subsequent oocyte formation in mice.
2. Meiotic Defects and their link to infertility:
● Meiosis interrupted: the genetics of female infertility via meiotic failure: This review categorizes
genetic variants associated with female infertility based on their disruption of specific meiotic
stages: (i) prophase I (e.g., SYCE1, SPO11), (ii) meiotic resumption (e.g., WEE1, MOS), (iii) meiosis
I chromosome segregation (e.g., BUB1B, MAD2L2), and (iv) meiotic cell-cycle regulation
(e.g., CDC25A, CDK2).
3. Targeting meiosis for fertility intervention:
● Dr. Judith Yanowitz: Studying Meiosis and its link to fertility: This ongoing research program
investigates manipulating meiotic processes to enhance fertility potential. The current focus involves
identifying markers for egg quality selection and exploring strategies to delay oocyte aging, potentially
extending reproductive lifespan.

30. Thanks!