Cell cycle & Gametogenesis

Dr Sharifa Abdul AzizFPSK, USIM2008/2009

Cell life cycle

• Cell : definition???• Single cell: at fertilization, 75 trillions at maturity.• By cell division --daughter cells(1/2)- mature to

adult- divides again.• Life span varies from hours to decades.• eg,. RBC-120days, neutrophil – 6-7hours, neurons,

heart -50-100years etc.• Highly adaptable.• Damaged by wear and tear(koyak), temp. changes,

chemicals, environ. stress.

Contd.• After sometime due to activation of suicidal gene in

nucleus cell self-destruct by themselves— APOPTOSIS(the death of cells ).

• DNA REPLICATION: duplication of cell’s genetic material done before any cell division.

• Mitosis : nuclear materials divide b/4 cell divide.• Meiosis : occurs only during the formation of the sex

gamete.

Interphase

• Brief period of mitosis alternating with interphase.• Interphase : majority of functional life in this

phase. During this phase cell undergoes its normal functions and prepares for cell division.

• Go phase : not preparing for cell division. Eg some skeletal muscle and most neurons - remain in this phase for indefinitely. Stem cells never.

• G1 phase (8 or > hrs) : apart from normal functions, duplication of organelles, protein synthesis done.

• S phase (6-8hrs) : DNA replications and synthesis of histones and other proteins in the nucleus.

Contd.• G2 phase (2-5hrs) : last minute protein synthesis.the

cell then enters M phase.• M phase : Mitosis means division and duplication of

the cell’s nucleus, division of cytoplasm to form two distinct new cells involves a separate but related process known as cytokinesis.

• MITOSIS 4 PHASE : Prophase, metaphase, anaphase and telophase.

• Prophase : chromosomes are so tightly coiled that it appears as individual structures under L/M- each chromatid is connected to duplicate copy by centromere, which is surrounded by kinetochore(protein).

Contd.• Nucleoli disappear.• Nuclear envelope disappear.• Spindle fibers appear between two centrioles.• Metaphase : chromatids moved to metaphase plate

(in centre of chromosomal microtubules)• Anaphase : centromere of each chromatid pair splits.• The two daughter chromosomes pulled towards

opposite ends of cell• Telophase : each new cell return to interphase stage.

Nuclear membrane reform, nucleus enlarge, chromosomes uncoil ,nucleolus reappear.

Contd.• Cytokinesis (motion of cell)• Cytoplasm division of daughter cells occur in late

anaphase. Cytoplasm constricts along the plane of metaphase plate- cleavage furrow. It contd. Through telophase resulting in - two separate and complete cells.

• Mitotic rate : number of cells in mitosis at any time.• Generally, the slower the mitotic rate, the longer

the life expectancy of a cell.• Stem cells : maintain the cell population by repeated

cycles of cell division relatively unspecialized, only function is production of daughter cells. Rate of division vary with type of tissue and demand for new cells.

Regulation of cell life cycle• Rate of cell division =rate of cell loss or destruction.

Mitotic rates are genetically controlled.• Stimuli for mitosis : may be internal (M-phase

promoting factors (MPF) or maturation – promoting factor. MPF formed from two proteins (Cdc2 + cyclin) .

• External stimuli : peptides (several hormones and variety of growth factors)

• Growth hormones all cells• Fibroblast growth factor (FGF) connective tissue• Cyclones from many tissue inhibition of cell

division.

The cell life cycle of a typical cell

Gametogenesis

• Human developmental process starts with fertilization.

• Fertilization process involved spermatozoa from the male and and oocyte from the female join to form the new product called Zigot.

• Before that, gametogenesis process occurs in male and oogenesis occurs in female.

Gametogenesis

• In male gametogenesis process undergoes two processes i.e : spermatogenesis and spermiogenesis.

• It starts only at puberty in male.• In female ,oogenesis undergoes one

process only and it starts at 3rd month of intrauterine life while the mother is pregnant. It ends at the time of birth and starts again at puberty.***

Spermatogenesis • SPEMATOGENESIS : Spermatogonia

(44+XY)mitosis 2 daughter cells(44XY) DNA replication*

• Each daughter cell-- primary spermatocyte (largest cell of the series)-- 1st meoitic division- 2ndry spermatocyte 2nd meiotic division-- spermatids (haploid nos).

• EACH SPERMATID: -- spermiogenesis- 4 sperms.

• Altogether -- one spermatogonium-- 8 sperms.

Spermiogenesis

• Final stage of spermatogenesis which sees the maturation of spermatids into mature, motile spermatozoa.

• Divided into 4 phases.• Golgi phase : the head forms at one end,

golgi creates enzymes - acrosome.• The other end thickened mid-piece where

mitochondria gathers and form axoneme(the central strand of a cilium or flagellum,) tail.

• Cap phase : the golgi app. surrounds condensed nucleus acrosomal cap

Gametogenesis & oogenesis comparison

Contd.• Acrosomal phase : one of centrioles

elongated tail. “ Manchette’ (microtubule) a temporary structure assist it.

• Sperm take its position as tail points towards the center of lumen.

• Maturation phase : the excess cytoplasm (residual bodies) is phagocytosed by Sertoli cells in the testis.

• Mitichondria – provide energy for motility.• Perinuclear theca- located in sperm head ,

maintain shape of head and func. molecules for oocyte activation.

Spermiation • Means the mature spermatozoa released in

to seminiferous tubules which removes the remaining cytoplasm + organelles.

• Mature sperms, but immotile.- transported - epididymis in testicular fluid+peristalsis contraction.

• Acquired motility here, but transport done by contraction of muscle.

• A glycoprotein coat over acrosome prevent it from entering egg. Capacitation of sperm by enz.FPP(ferti. promoting peptide)fr. Male n heparin from female tract can remove this coat.

Overview • Spermatogenesis 4

gametes(23X,23X,23Y,23Y)=46XY• Spermiogenesisround spermatidelongated,

loose cytoplasm, transform golgiacrosome,organize microtubulemotility, segregate mitoc.energy in tail.

• Oogenesis (mitosis & meiosis)single haploid egg +3polar bodies.in meiosis1—extra DNA exclude as 1st PB, meiosis 2, extra DNA 2nd PB. PB.

• Polar B – not gamete, no other function except to dispose extra DNA.

Spermatogenesis abnormalities• Oligospermia : low s. count, i.e < 20million sperm

after 72 hrs abstinence from sex.(normal-200-300millions/ejaculation)

• Azoospermia : complete absence of sperm in the semen.

• Immotile cilia syndrome – lack of motility.• Globozoospermia : round headed spermatozoa -

acrosomal malformation.• Sperm : 10% have defects. The head or tail may be

abnormal. Giant s, dwarf s, double-head joined,

Normal sperm

Abnormal sperm

Fixed & stain human sperm

Oogenesis • Process of production of a mature ovum ready

for fertilization by sperm. Starts from puberty end at menopause during which one mature ovum is developed (rt or lt) every 28 days.

• Occurs in the cortex of ovary. Primordium follicle primary follicleoogonium.

• Oogonia ; primitive female germ cells.• Each oogonium surrounded by flat epithelial

cells- primary oocyte.• Oogenesis : 2processes• 1. maturation of primary

oocytemature(haploid chromosome).

Contd. • 2. maturation of follicular cells around the

oocyte-- mature follicle(grafian follicle) for protection of ovum + production of hormones.

• Oogenesis (44xx)- growth & differentiation of oogonium-mitosis primary oocyte----after DNA replication 1st meiosis secondary oocyte +1st polar bodies(22x) 2nd meiosisovum (22x)+2nd polar bodies(22X).

• Ist polar bodies second polar bodies (22x+22x). All polar bodies degenerate and disappear. Function of polar bodies- just to get rid of DNA.

Development of follicular cells• Simple flat epithelial cell surround primary oocyte

(primordium follicle)- enlarge bc cuboidal (primary follicle) columnar (secondary follicle) - many layers.

• The follicular cells deposit glycoprotein substance which surround the oocyte- zona pellucida (acellular layer) , follicular cells k/a granulosa cells.

• Small irregular spaces appear in granulosa cells join large cavity (follicular cavity). oestrogen hormones. Now it is called “Graffian follicle). Oocyte surrounded by follicular cells: cumulus oophorus.

Oogenesis

Abnormal oogenesis

• Binucleated oocyte twin

• Trinucleated oocyte triplets

Oogenesis

Fertile – 400-500

Good looking egg

Immature egg

General knowledge• Ejaculate 3.5ml, 200-600millions sperm• By volume <10% sperm• Accessory glands- 60% seminal vesicle,

10% bulbourethral, 30% prostate.• Ovary :oogonia7millions b4 birth, 2millions

at birth, 300-400K b4 puberty---few follicles at late 40. Primodium f-> 150days---primary F->120days --secondary F(antral F)->14-15days ---dominant f ovulation. 10% of 400k will be released through reproductive life (fertile – 400-500)

Abnormalities during Meiosis• 1. Non-disjunction- failure of two members of a

pair of homologous chromosomes to separate during 1st meiosis division.eg. 22 + 24.

• 22+23,X-- 45monosomy.• 24 +23,X--- 47trisomy, trisomy of Ch.21

Down’s syndrome.• Trisomy of X ch.XXX• Monosomy of X ch- +X from sperm

45+XOturner’s syndrome.

Down’s syndrome

Klinefelter syndrome• Male at puberty.• 47XXY, 48 XXXY• Testicular atrophy.• Gynecomastia.• 1:500 males• Cause – non-disjunction of

XX homologous.

Klinefelter syndrome

Turner’s syndrome• 45,XO, phenotype female• (-) of ovaries.• Short stature.• Webbed neck, • Broad chest with widely

spaced nipples.• Increase carrying angle• Skeletal deformities.• Cause-non-disjunction in

male gamete.