Mammalian sex determination, development 1 Flashcards
vegetative reproduction
- used by bacteria, plants, some invertebrates
- budding (yeast), fission (bacteria), fragmentation
parthenogenesis
reproduction using eggs but without sex (eggs never fertilized by a male)
advantages/disadvantages of parthenogenesis
- advantages: pass genes on intact (genetic immortality), rapidly populate new environment
- disadvantages: not good long-term
list 2 theories about why sexual reproduction persists
- muller’s ratchet
- the red queen
muller’s ratchet
- theory for why sexual reproduction persists
- most genetic mutations are deleterious –> accumulate
- populations will have rapidly decreasing fitness
- “mutational meltdown of clones”
- sexual reproduction allows genetic mixing and repair
the red queen hypothesis
- theory for why sexual reproduction persists
- biological enemies like bacteria and parasites constantly evolve and reproduce much faster –> genetic mutations become prevalent quickly
- our defense is to be genetically variable, more so with each generation
why are 3+ sexes not seen?
- can exist
- unstable and usually revert to 1 or 2 sex system
types/levels of sex (8)
- genetic (chromosomes)
- gonadal (ovary or testis)
- germ cell (egg or sperm)
- hormonal (estrogen or androgens)
- phenotypic (genetalia, secondary sex characteristics)
- somatic (brain)
- behavioral
- legal
3 steps in mammalian sex determination
- genetic (chromsomal) sex determined at time of fertilization (X or Y sperm)
- sex determination occurs when bipotential/indifferent gonad is put on male or female pathway (Y chromosome present or not)
- sexual differentiation of male/female phenotype from hormone secretions of ovary or testis
what method of genetic sex do mammals utilize
dominant Y, single pair method –> can’t use environmental cues or estrogens due to development of viviparity and a placenta (presence or absence of Y determines sex)
when is genetic sex determined in mammals
at the time of fertilization and depends on whether and X or Y bearing sperm fertilizes the oocyte
what is the testis-determining factor a product of
the gene SRY (sex-determining region Y chromosome) –> tip of Y chromosome
SRY gene info
- single copy gene that encodes SRY protein
- transported to nucleus where it binds DNA to induce a bend
- expressed in urogenital ridge prior to gonadal differentiation
- expression is independent of the presence of primordial germ cells
other functions of Y chromosome
- transgenic XX mice that have SRY insert develop as males with penis/testis but are sterile due to lack of spermatogenesis
- increase in height
- blood pressure and cholesterol
- “genetic junk”
3 sets of kidneys in embryonic development
- pronephros
- mesonephros
- metanephros
pronephros
- degenerates
- duct persists as the mesonephric duct
mesonephros
- contains tubules induced to form by the residual mesonephric duct with which they communicate
- degenerates except for some of the caudal tubules and the mesonephric duct
metanephros
develops into kidney and ureter
where do gonads develop rom
urogenital ridge –> a strip of mesenchyme adjacent to the ventromedial surface of the mesonephric kidney
how are cellular cords of the indifferent gonad formed
mesenchyme (urogenital ridge) is invaded by coelomic mesothelial (epithelial) cells, which along with cells from degenerating mesonephric tubules, form the cellular cords of the indifferent gonad
what are transcription factors acting on
somatic cells –> don’t need germ cells to form the indifferent gonad
is the stage of the undifferentiated gonad prolonged in males or females
females
4 cell lines in the final gonads
- 3 somatic cell linages, 1 germ cell lineage
- somatic: supporting cells, steroid-producing cells, mesenchymal cells
- germ: spermatogonia or oogonia
3 somatic cell linages in gonads
- supporting: sertoli in male, follicular granulosa in female
- steroid-producing: leydig in male, theca in female
- mesenchymal: peritubular myoid and vasculature of testis, connective tissue and vasculature of ovary
what is the indifferent gonad also called
bipotential gonad because each cell type can potentially differentiate down either a male or female line
what is the fate of the bipotential gonads decided by
the fate of the supporting cells (sertoli v granulosa) –> 2 competing cascades
male genetic cascade factors
- Sox9
- fibroblast growth factor-9 (Fgf9)
female genetic cascade factors
- Wnt-4
- R-spondin1 (RSPO1)
- FOXL2
function of SRY
tip the balance in favor of the male pathway by kick-starting (up-regulating) Sox9 before female cascade can get going
indifferent gonad in lower animals
- 2 regions: cortex and medulla
- cortex differentiates into ovary
- medulla differentiates into testicle
function for faster male growth
male embryo needs to more rapidly get to the stage of gonadal determination to avoid being involved in (or to escape) the female pathway
earliest noted change during sex determination
- doubling in the size of the gonad in XY embryos compared to XX counterpart
- due to massive proliferation of pre-sertoli cells directed by Sry
- proliferation required for formation of testicle and inhibition of female pathway
what must be present in gonad for testicular formation
- > 30% of cells in gonad must be Sry-expressing sertoli cells or a testicle cannot form
- an ovary will result otherwise
what is protein product of Sry working together with that of SF-1
up-regulation of Sox-9, which is then continuously expressed –> causes differentiation of the supporting cells into sertoli cells
what does the fact that only 30% of supporting cells need to express Sry imply
paracrine signals from these cells can recruit other supporting cells (Sry negative) to the sertoli cell pathway
what do newly differentiated sertoli cells do
- rapidly aggregate to form the testis cords –> testicle will differentiate irrespective of whether germ cells are present
- induce leydig cells to differentiate and partition to the interstitium
function of myoid cells
- migrate into genital ridge from the mesonephros and surround the cords
- separate the sertoli and leydig cells
where do germ cells go (male)
drawn into the medulla and then into the sex cords which become prominent –> cords become future seminiferous tubules
are germ cells required for the formation of testes and ovaries
not for testes but required for ovaries –> in the absence of oocytes, ovarian follicles fail to develop, the supporting cells degenerate, and a streak gonad is formed
in females, what do cords of mesonephric tissue do
colonize the central part of the presumptive gonad, pushing the germ cells to the periphery (cortex) –> germ cells remaining in central region degenerate
what do cells in female cortex do
multiply and differentiate and establish cortical dominance with clusters (nests) of germ cells (oogonia)
what happens when female germ cells enter meiosis
- do so fairly synchronously in wave from anterior to posterior
- become oocytes
- cells within clusters move apart
what do oocytes do
induce supporting cells (pre-granulosa) to differentiate as granulosa cells rather than sertoli cells –> oocyte surrounded by granulosa cells is now a follicle
what does the timing of development of actual follicles depend on
the species-specific time when the oocytes reach the diplotene stage of first meiotic prophase –> during fetal life or post-natally
what is follicle formation dependent on
the presence of germ cells
what do female supporting cells do
maintain the structure and prevent formation of male gonadal features –> absence of supporting action leads to apoptosis and a streak gonad
2 ways to get a streak gonad
- never having germ cells in the ovary
- losing germ cells early in development
how is male pathway suppressed
RSPO1 cooperates with Wnt4
origin of the primordial germ cell
primitive ectodermal cells of the inner cell mass (epiblast) under the influence of bone morphogenic protein (BMP)
where do primordial germ cells go
migrate into the dorsal yolk sac endoderm and begin proliferating, then migrate through the hindgut epithelium and mesenteries, to the ventral mesonephros and into gonad
what happens at the end of primordial germ cell migration
they become concentrated in the cortical regions of future females and preferentially in the medulla of genetic males –> multiply during migration, more division in the gonad
division of germ cells in ovary
- during multiplication phase in gonad, some oogonia will already have entered the first mitotic division leading to the formation of primary oocytes
- soon after birth and wave of atresia, all remaining germ cells in the ovary will be primary oocytes arrested in the first meiotic prophase
division of germ cells in the testis
- meiosis does not commence until puberty
- germ cells enter mitotic arrest as prospermatogonia when the female germ cells are entering meiosis and resume mitotic proliferation post-natally
