Professor Alfred Cuschieri

Department of Anatomy

University of Malta




o       Explain the significance and importance of meiosis in sexual reproduction

o       Identify the different stages of gametogenesis in males and females in micrographs of testis and ovary

o       Name the stages at which the first and second meiotic divisions take place

o       Outline the stages of spermiogenesis

o       Name the functions of Sertoli cells and granulosa cells

o       Define the stages at which meiotic arrest in oocytes normally occurs

o       Identify the components of developing ovarian follicles and of the oocyte at the time of ovulation

o       Discuss the mechanism of non-disjunction in numerical chromosome aberrations.



Sexual Reproduction


Sexual reproduction involves the formation of male and female gametes  and the the mechanisms necessary for the gametes to come together and fuse to form one cell that represents the beginning of a new individual with a distinct genetic identity.

Preparation for pregnancy involves two main programs of events:

1. Gametogenesis  

o       the process of formation of the male and female gametes

o       occurs in the gonads (ovary or testis)

2. Cyclic changes in the female genital tract  

o       the ovarian cycle

o       the uterine cycle

Prepration for pregnancy has three important practical applications

1. Controlling undesired pregnancies  - Contraception

2. Treating Infertility  - Assisted conception

3. Transmission of genetic disease

- transmission of inherited traits

- disorders of meiosis

All these applications have profound medical, social and ethical implications


One Essential Question: Why is sexual reproduction  necessary?

The main purpose of sexual reproduction is the formation of offspring who are genetically different from one another and from their parents.

Meiosis is the fundamental process underlying sexual reproduction.  It involves two essential outcomes:

1. Reduction Division the process in which each gamete receives a haploid set (n) of chromosomes and genes.

The diploid number (2n) is restored on fusion of two gametes.

2. Rearrangement of genes on the maternal and paternal chromosomes.

This ensures that the offspring are genetically different  from one another.


Meosis involves four main events, and two cell divisions.  (In the following diagram only one pair of homologous chromosomes is shown, to represent 23 pairs in humans).












1.      DNA replication precedes meiosis, and occurs in the S phase, as in all cell divisions.  Recall that the chromosomes in the parent cell contains a diploid set of chromosomes (2n chromosome number and 2c amount of DNA).  Following replication, there are still 2n chromosomes, but each chromosome consists of two chromatids, and has 2c DNA.




2. Pairing of homologous chromosomes and crossing over of chromosome segments occur during prophase of meiosis. They are crucial event in meiosis.


























The complex of a homologous chromosome pair consisting of four chromatids is a tetrad.  The result of crossing over is that there are now four recombinant chromatids.






3. Separation of chromosomes occurs as a result of the first meiotic division. The two resulting daughter cells each have one of a pair of replicated chromosomes, or a haploid set (n) with a total of 2c DNA. 


4. Separation of chromatids occurs as a result of the second meiotic division, and give rise to four daughter cells, each containing a haploid set of chromosomes (1n; 1c) amount of

Meiosis occurs in the germ cells.  As a result of meiosis, four daughter cells  or gametes, are produced, each containing one of a pair chromosomes and  all containing different chromosomes.  Although the above diagram illustrates only crossing over between the adjacent chromatids, in fact crossing over also occurs between the two “outer” chromatids, and at different sites from the other pair, so that all four daughter cells are different from one another and from their parents. Pairing of the two “outer” chromatids is possible because, in 3 dimensions these would also be adjacent to one another. 


Genetic Imprinting

In all diploid cells of an individual the chromosomes occur in homologous pairs.   One chromosome of each pair is derived from the mother and the other from the father. The maternal and paternal chromosomes are morphologically indistinguishable but have important functional implications because the expression of some genes is dependent on whether they are on the maternal or the paternal chromosome.  This is termed genetic imprinting



Gametogenesis is the process of formation of gametes from the germ cells in the testes and ovaries.  Many principles of gametogenesis are the same in both males and females, and will be considered first. Gametogenesis is divided into four phases:


1. Extra-gonadal origin of primordial germ cells

2. Proliferation of germ cells by mitosis

3. Meiosis

4. Structural and functional maturation of the ova and spermatozoa


Primordial Germ Cells


o       Are the earliest precursors of all germ cells

o       Are formed in the early stages of embryonic development

o       Are first recognizable close to the hindgut as large cells with high alkaline phosphatase

o       Proliferate and migrate into the gonad (testis or ovary)

o       Differentiate into male or female germ cells (determined by sex chromosomes)



The nomenclature of the developmental stages of gametogenesis is similar in male and female germ cells.  It is summarised in the following diagram.
















In males the spermatids, the products of the second meiotic division, undergo morphological changes, known as spermiogenesis,  during which they become motile spermatozoa.  There is no corresponding stage in females.

The timing of the developmental stages of gametogenesis, and the number of gametes produced are very different in male and female germ cells.

o       In the male spermatogenesis occurs from puberty to old age, producing immense numbers of spermatozoa at an average rate of 1.5 million spermatozoa per minute.


o       In females oogenesis begins in early foetal life. All oocytes ever to be formed in females are produced during foetal life. Many of them degenerate with time and at birth the ovaries contain about 2 million oocytes.   All the oocytes go into meiotic arrest when they reach the first meiotic division during foetal life. The primary oocytes remain in the prophase of the first meiotic division until the time of puberty, when they are gradually released to complete meiosis at regular intervals known as the ovarian cycle. On the average only one oocyte matures during each cycle, which occurs at approximately monthly intervals, so that the total amount of oocytes to be ovulated is about 500 oocytes in a lifetime.


Spermatogenesis is the process of formation of the male germ cells.  It occurs in the seminiferous tubules of the testes.  The developmental stages of the male germ cells can be observed sequentially from basement membrane to lumen.











The sertoli cells are supporting cells that have several functions.

They form the blood-testes barrier: nutrients, and circulating substances do not directly reach the germ cells; the Sertoli cells determine which substances reach the germ cells. The spermatogonia are outside the blood-testis barrier.  They form invaginations surrounding the spermatocytes, spermatids and developing spermatozoa and are nutritive to them. They also produce antigen-binding proteins, which are necessay for spermiogenesis. 

The figure below is a light micrograph of  a seminiferous tubule

Spermiogenesis is morphological development of  spermatids to spermatozoa. It involves:

a.      Nuclear changes - The nucleus becomes condensed and heterochromatic -histones are replaced by protamines, which allow a high degree of DNA compaction and makes DNA inaccessible for transcription

b.      Cytoplasmic changes – These are directed to the formation  of a  motile sperm cell capable of penetrating the ovum and involves the following changes:


o       The Golgi apparatus at one pole of the cell forms an acrosome containing proteolytic enzymes

o       The centrriole at the opposite pole organises the formation of microtubules to form a flagellum

o       Alignment of mitochondria in a spiral around the base of the flagellum – this forms the mid-piece of the spermatozoon

o       The excess residual cytoplasm accumulates at one side of the cell and becomes detached to form a residual body







At birth the ovary contains primordial follicles. They consist of a primary oocyte surrounded by granulosa cells.

Gap junctions connect the oocyte to surrounding granulosa cells.

The gap junctions permit passage of amino acids, glucose and metabolites for growth of the oocyte.

The follicular cells secrete a meiotic inhibitory factor that is responsible for the first meiotic arrest.



The developing oocyte undergoes two meiotic arrests:













The Ovarian follicle consists of the following:











The zona pellucida:

o       Is  secreted by the oocyte

o       Consists of glycoprotein and glycosaminoglycans

o       Contains sperm receptors necessary for fertilization



The oocyte cytoplasm contains:

- numerous ribosomes (produced by r-DNA amplification in nucleolus)


- Yolk droplets ( nutritive)


- Cortical granules  (formed in the Golgi apparatus). 


Cortical granules are released on penetration of the vitelline membrane by a sperm. They cause a change in the zona pellucida to prevent double fertilization




The Graafian follicle (tertiary follicle) is distended with liquor and points at the surface of the ovary like a blister. 

Rupture of the follicle occurs at ovulation releasing the secondary oocyte.  At the time of ovulation the second meiotic division is still not completed.  After ovulation

 the secondary oocyte is surrounded by a corona radiata.



Abnormalities in meiosis may give rise to numerical chromosome abnormalitites. Non-disjunction is the usual mechanism by which abnormalities in chromosome number may occur.  The following diagram illustrates chromosome 21 in meiosis I and II in (a) normal gametogenesis and (b) non-disjunction in meiosis I.  Failure of separation of the chromosomes results in a secondary oocyte or a secondary spermatocyte with two chromosomes 21, which will form trisomy 21 after fertilisation.  The other secondary oocyte or spermatocyte has does not contain a chromosome 21, and after fertilization, will result in monosomy 21.  This is incompatible with survival and this condition is therefore not seen.  Non-disjunction also occurs in common trisomies e.g. trisomy 18 or trisomy 13.
















Non-disjunction may also occur in meiosis II, resulting from failure of separation of the chromatids, as shown in the following diagram.  This type of non-disjunction is rare.