Sex determination + fertilization (lec 9/10) Flashcards
The embryonic mammalian gonad is originally __________. It is neither male nor female, but has the potential to be either.
If the cells have an X and a Y chromosome, the gonad becomes a ______ that makes _______ and the hormones that promote a ______ phenotype.
If the cells have two X chromosomes and no Y chromosome, the gonad becomes a ______ that makes _______ and the hormones that promote a ______ phenotype.
BIPOTENTIAL
Testis; sperm; male
Ovary; eggs; female
(T/F) The conversion of the GENITAL RIDGE into the BIPOTENTIAL GONAD requires multiple genes. If these genes are not present, the organisms lack gonads.
True!
How can the bipotential gonad be moved into the FEMALE PATHWAY (ovary development)?
The bipotential gonad is moved into the FEMALE PATHWAY by the Wnt 4 and Rspo1 genes, which promote the accumulation of β-catenin.
How can the bipotential gonad be moved into the MALE PATHWAY (testis development)?
The bipotential gonad can be moved into the MALE PATHWAY by the Sry gene (on the Y chromosome) which triggers the activity of Sox9.
Under the influence of ________, the _________ duct differentiates into the female reproductive tract, the internal and external genitalia develop, and the offspring develops the ___________ sex characteristics of a female.
Estrogen (first from the mother, then from the fetal ovaries); Mullerian; Secondary
Briefly answer the following questions regarding the development of male secondary characteristics:
1) What hormone does the testis make to regress the Mullerian duct?
2) What does testosterone do?
1) Anti-Mullerian Hormone (AMH)
2) Testosterone causes DIFFERENTIATION of the WOLFFIAN duct into the male INTERNAL genitalia. In the urogenital region, testosterone is converted into DIHYDROTESTOSTERONE (DHT) which causes MORPHOGENESIS of the penis, prostate gland, and scrotum.
Genital ridge has converted into a bipotential gonad at ___ weeks in embryo, which has an expanded epithelium in ___ weeks.
There is a testis/ovary development in week ___ embryo!
4; 6
8
What is the difference in a 20-week embryo that has developed a testis vs an ovary in week 8?
Testis: by week 20, the testis cords ARE CONTINUOUS with the testis and CONNECT with the WOLFFIAN DUCT.
Ovary: by week 20, the ovary DOES NOT CONNECT to the WOLFFIAN duct and a new cortical FOLLICLE CELLS surround the germ cells that have migrated into the genital ridge.
Sry gene is important for the male development pathway (testis development).
What happens when it is not present?
When Sry is not present, TFs in the GENITAL RIDGE activate Wnt4 and Rspo1 (genes important for ovary development).
Wnt4 activates the Wnt pathway which is made more efficient by Rspo1. The Wnt pathway causes the accumulation of β-catenin, which stimulates further Wnt4 activity.
The continual production of β-catenin both INDUCES the transcription of ovary-producing genes and BLOCKS the TESTIS-DETERMINING pathway by interfering with the Sox9 activity.
What is the Follistatin gene?
Follistatin gene is one of the targets of the Wnt pathway, whose product organizes the GRANULOSA cells of the ovary.
*Key molecules for ovary formation
Sry gene is important for the male development pathway (testis development).
What happens when it is present?
If Sry is present, it blocks β-catenin signaling (thus halting ovary development) and, along with Sf1, ACTIVATES the SOX9 gene.
Sox9 activates Fgf9 synthesis, which stimulates TESTIS DEVELOPMENT, BLOCKS Wnt4, and promotes further Sox9 synthesis.
Sox9 also prevents β-catenin’s activation of ovary-producing genes.
Sry can also activate other genes that help generate SERTOLI cells.
______/______ loop specifies the ovaries, _____/____ loop specifies the testes.
Wnt4/β-catenin
Sox9/Fgf9
Generally in an XX female the Sry gene is not expressed and the external genitalia are female.
What happens if you express Sry in a XX female (transgenic XX/Sry)?
The external genitalia of the transgenic XX/sry mouse are MALE and are essentially the SAME as those in XY male.
Normally, a wildtype XY embryo expresses the Sox9 gene in the genital ridge at 11.5 days, AMH in the embryonic gonad Sertoli cells at 16.5 days and eventually forms descended testes with seminiferous tubules.
A wildtype XX embryo shows neither Sox9 expression nor AMH. It constructs ovaries with mature follicle cells.
What happens to an XX embryo with the Sox9 transgene inserted?
An XX embryo with the sox9 transgene inserted EXPRESSES SOX9 and has AMH in 16.5-day Sertoli cells!!
It has descended testes, but the seminiferous tubules LACK SPERM (due to the presence of two X chromosomes in the Sertoli cells)
(T/F) At day 11, Sry protein is seen in the centre of the genital ridge. At day 11.5 Sry expression increases and Sox9 expression is activated. By day 12.0 Sox9 protein is seen in the same cells that expressed Sry. By day 13.5, sox9 is seen in those cells of the TESTIS TUBULE that will BECOME SERTOLI CELLS.
True!
Sry –> Sox
1) What kind of hormone is testosterone?
2) What does it do inside the cytoplasm of a cell (what does this lead to)?
1) Testosterone is an ANDROGEN (masculinizing) STEROID HORMONE that can travel to cells through the blood.
2) Inside the cytoplasm of a cell, it binds TO ITS PROTEIN RECEPTOR (androgen receptor) displacing other proteins. This allows the androgen receptor to DIMERIZE and ENTER THE NUCLEUS. The bound testosterone permits the receptor protein to function as a TRANSCRIPTION FACTOR, binding to particular genes to produce the male phenotypes.
What happens in complete and partial ANDROGEN INSENSITIVITY SYNDROME?
In complete and partial androgen insensitivity syndrome, MISSENSE mutations are distributed throughout the EIGHT EXONS of the androgen receptor gene, but localized mainly in exons that ENCODE the DNA-BINDING and LIGAND-BINDING DOMAINS where their functional effect is great because of the ordered structure of these domains.
Briefly answer the following questions of Drosophila somatic sex determination:
1) What is the Sxl gene?
2) What activates the Sxl gene and where?
3) What do the Tra proteins do?
1) Sex-lethal (Sxl) gene enables the SPLICING of the transformer-1 (tra-1) pre-mRNA into functional proteins.
2) Transcription factors from the X chromosomes activate the Sxl gene in FEMALES (XX) but NOT IN MALES (XY)
3) The Tra proteins process DOUBLESEX (dsx) pre-mRNA in a female-specific manner that provides most of the FEMALE BODY with its sexual fate.
*Sxl pathway influences formation of female specific proteins that suppress male differentiating genes and also activates female differentiating genes.
_________, ________, and _________ are all part of the genetic cascade of gonadal sex determination.
The ___________ pattern of _______ determines the secondary characteristic of courtship behaviour.
The ________ proteins splice the FRUITLESS pre-mRNA to make male and females forms of the protein in the fly brain.
Sex-lethal, transformer, doublesex
Transcription; Fruitless
Transformer
(T/F) Males do not have a functional fruitless protein while females do.
False!
Transformer regulates fruitless. There is a functional transformer protein in females, but not in males.
The functional transformer protein induces a stop codon in the fruitless gene which leads to a non-functional protein in females.
Because there is no functional transformer protein in males, stop codon is not induced in male fruitless genes. Thus males have fruitless protein.
Are these Drosophila sex-determining proteins found in males, females of both?
1) Sex-lethal
2) Transformer
3) Doublesex
4) Fruitless
1) Sex-lethal: only FEMALES
2) Transformer: only FEMALES
3) Doublesex: BOTH
4) Fruitless: only MALES
Can vertebrates undergo sex determination INDEPENDENT of genetic variation?
Yes, they can!
This is due to development plasticity.
Ex. Turtles and alligators undergo sex determination due to environmental conditions they are raised in. The temperature influences the genders.
*climate change can lead to extinction.
