Postgraduate Training Course in Reproductive Health/Chronic Disease
C. de Vantéry Arrighi, H. Lucas
See also presentation
I. Definition of gametogenesis
Gametogenesis describes and includes all the processes involved in the production of reproductive cells or gametes (spermatozoa or oocytes) from stem cells, the primordial germ cells (PGC). Gametogenesis include spermatogenesis (production of spermatozoa) and oogenesis (production of oocytes/eggs).
The genesis of two sexes depends on genetic differences
The genetic determinant of sex is on Y chromosome :
- If the Y chromosome is present then the individual develops the male gonads, testis
- If the Y chromosome is absent the individual develops the female gonads, ovaries
Y-chromosome activity alone is sufficient to determine gonadal sex
Determination of gonadal sex (sexual dimorphism) is the issuing of an instruction by the Y-chromosome saying : « make a testis ».
Y chromosome is small and most of its DNA is heterochromatic (very condensed and incapable of synthesizing RNA), therefore other genes lying on other autosomal chromosomes and even on X chromosome are required to make an organ as complex as testis, but the Y chromosome contains the « switching » or controller gene, which regulates the expression of all other structural genes by deciding whether and when they should become activated.
- Men 46 XX, translocation of a piece of Y conatining SRY on an autosome or X
- Women 46 XY, deletion/mutation on short arm of Y corresponding to SRY
The testis-determining gene : SRY : «Sex-determining Region Y gene» :
SRY is located close to the end of the short arm of the human Y chromosome. This gene encodes a protein which binds specific sequences of DNA, induces DNA bending after binding and is localized to the nucleus, thus characteristic of transcriptional regulators that influences other downstream genes.
The two gonads develop from a bipotential precursor through the differential action of SRY in males
The early development of the gonad proceeds indistinguishably in males and females.
In both sexes the gonads are derived from a common precursor made up of two distinct tissues :
- Somatic mesenchamal tissues, which form the matrix of the gonad
- Primordial germ cells (PGC), which migrate and colonize this matrix to form the gametes
In human embryo :
- At 3 weeks : undifferentiated PGC are identifiable in the epithelium of the yolk sac (morphology and alkaline phosphatase activity)
- At 4 weeks : PGC migrate by amoeboid movements from the yolk sac to the genital ridges and proliferate by mitosis
- PGC induce the genital ridge to differentiate into a primitive germinal epithelium, and become embedded in it, forming primary sex cords. The gonads are then histologically distinct, bipotent that may become testis or ovary.
- At 8 weeks : ovary and testis are histologically distinct
In male : gene products directed by activation of the SRY gene cause the undifferentiated sex cords enlarge, split and begin to form the primitive testis. PGC begin to differentiate into spermatogonia.
In female : PGC begin to differentiate into oogonia within follicles.
The differentiation of two sexes depends on the endocrine activity of the fetal testis
The male and female internal genitalia develop from different unipotential precursors through the actions of androgens and MIS (« Müllerian Inhibiting Substance ») :
- The male and female external genitalia develop from a single bipotential precursor through the actions of androgens
- Exposure of female fetuses to androgens will « masculinize » their external genitalia
- Castration (or suppression of endogenous androgens) of males fetuses will « feminized » their external genitalia
Pre- and postnatal growth of the gonads is slow until puberty
The testis migrate to a scrotal position :
- cryptorchidism : spermatogenesis is arrested, testicular metabolism is abnormal and the risk of testicular tumors increases (prolonged warming)
Testicular growth and activity are important for male development
Most ovarian germ cells die before puberty and all of them enter meiosis
The ovary is not essential for prepubertal development