The Questions of Developmental Biology

Snapshot Summary: Sex Determination
1. In mammals, primary sex determination (the determination of gonadal sex) is a function of the sex
chromosomes. XX individuals are females, XY individuals are males.
2. The Y chromosome plays a key role in male sex determination. XY and XX mammals both have a bipotential
gonad that makes the primary sex cords. In XY animals, these cords continue to be formed within the gonad, and
eventually differentiate into the Sertoli cells of the testes. The interstitial mesenchyme becomes the Leydig cells.
3. In XX individuals, the internal sex cords degenerate, and a second set of cortical sex cords emerges. These
remain on the periphery of the gonad. Germ cells enter the sex cords, but will not be released from the gonad
until puberty. The epithelium of the sex cords becomes the granulosa cells; the mesenchyme becomes the thecal
cells.
4. In humans, the SRY gene is the testis-determining factor on the Y chromosome. It synthesizes a DNA-binding
protein that is thought to compete with the DAX1 protein. It is thought that if SRY is produced at a high enough
level, it activates (either directly or indirectly) the SF1 gene and inhibits the WNT4 gene.
5. The SF1 product is believed to activate the SOX9 gene, as well as several other genes involved in synthesizing
steroid hormones and anti-Müllerian duct hormone (AMH). SOX9 may organize the genital ridge epithelium to
form testes, but the corresponding ovary-forming genes have not yet been found, although the WNT-4 gene may
be important in this regard.
6. Secondary sex determination in mammals involves the hormones produced by the developing gonads. Under
estrogenic stimulation, the Müllerian duct differentiates into the oviducts, uterus, cervix, and upper portion of the
vagina. In male mammals, the Müllerian duct is destroyed by the AMH produced by the Sertoli cells, while the
testosterone produced by the Leydig cells enables the Wolffian duct to differentiate into the vas deferens and
seminal vesicle. In female mammals, the Wolffian duct degenerates because of the lack of testosterone.
7. The conversion of testosterone to dihydrotestosterone in the genital rudiment and prostate gland precursor
enables the differentiation of the penis, scrotum, and prostate gland.
8. Individuals with mutations of these hormones or their receptors may have a distinction between their primary
and secondary sex characteristics.
9. In Drosophila, sex is determined by the ratio of X chromosomes to autosomes, and the Y chromosome does
not play a role in sex determination. There are no sex hormones, so each cell makes a sex determination decision.
10. The Drosophila Sxl gene is activated in females (by proteins encoded on the X chromosomes) and is
repressed in males (by factors encoded on the autosomes). Sxl protein acts as an RNA splicing factor to splice an
inhibitory exon from the tra transcript. Therefore, female flies have an active Tra protein, while males do not.
11. The Tra protein also acts as an RNA splicing factor to splice exons of the doublesex transcript. The doublesex
gene is transcribed in both XX and XY cells, but its pre-mRNA is processed to form different mRNAs,
depending on whether Tra is present. The proteins translated from both messages are active, and they activate or
inhibit transcription of a set of genes involved in producing the sexually dimorphic traits of the fly.
12. In turtles and alligators, sex is often determined by the temperature during the time of gonad determination.
Since estrogen is necessary for ovary development, it is possible that differing levels of aromatase (the enzyme
that can convert testosterone into estrogen) distinguish male from female patterns of gonadal differentiation.
13. In some species, such as Bonellia and Crepidula, sex determination is brought about by the position of the
individual with regard to other individuals of the same species.