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gametogenesis
- development of mature gametes = sperm and eggs
- includes processes of mitosis, meiosis, morphogenesis, differentiation
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PGC
where do they appear?
what do they express?
- primordial germ cell
- germ line is separated from somatic cells during the 2nd week post-fertilization
- appear in epiblast of pre-embryo
- appear several weeks before gonad appears
- express TF Oct4
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PGC migration
- migrate during 3rd and 4th weeks
- migrate through yolk sac, hindgut, and dorsal mesentery
- arrive at gonadal ridge at week 5
- chemotaxis is one likely mechanism (w/c-kit and SCF)
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what can happen if PGCs don't migrate correctly to the gonad?
may become germ cell tumors (teratomas and teratocarcinomas) in ectopic locations
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c-kit
SCF
- c-kit is a receptor
- SCF (stem cell factor) is the ligand for c-kit
- cells expressing c-kit and SCF surround PGCs along their migration pathway
- humans with loss of function mutations in c-kit are infertile
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Oct-4
a transcription factor expressed by PGCs
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BMP-4
required for activating migration of PGCs
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when do male germ line cells enter meiosis?
after puberty
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Piebald Syndrome
defect in pigmentation due to mutation in c-kit
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lines of evidence supporting role for c-kit in migration and proliferation of PGCs
- correlation: associated in time and location with migration pathways
- necessary: mutations lead to mice who are sterile, anemic (blood stem cell defects), and have pigmentation defects (neural crest cell defects - migration)
- sufficient: adding SCF to PGCs in vitro rescues cell locomotion defects
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gonadal environment
testes or ovary - environment exerts profound influence on the subsequent development of the germ cell to enter either oogenesis or spermatogenesis
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retinoic acid (RA)
Stra8
- RA = signaling molecule, meiosis inducing substance
- Stra8 = TF
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spermatogenesis
spermatogonia (mitosis) primary spermatocytes (meiosis I) secondary spermatocytes (meiosis II) spermatids (spermiogenesis) spermatazoa
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stem cell properties
- differentiate
- self-renew
- spermatogonia are stem cells
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Sertoli cells
- in close association with male germ line cells through all stages of spermatogenesis
- provide a niche for spermatogenesis
- function to suuport, nourish, and protect male germ line
- synthesize and secrete androgen binding protein (ABP)
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ABP
- androgen binding protein
- allows sufficient testosterone within seminiferous tubules for spermatogenesis
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Leydig cells
- in close proximity to Sertoli cells
- outside seminiferous tubule
- somatic cells that produce testosterone
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spermatids
- haploid
- connected via cytoplasmic bridges and share proteins
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spermiogenesis
process of haploid spermatid undergoing morphogenesis into fully formed spermatozoon
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parts of a spermatozoa
- acrosome
- protamine-rich nucleus (protamine is a sperm-specific chromatin)
- mitochondrial midpiece
- flagellar tail
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when do sperm become motile?
- immotile in the testes
- following ejaculation, sperm undergo capacitation in the female reproductive tract
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paternal age effect on reproduction
increase in achondroplasia, Marfan, schizophrenia
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