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MolBio (Fach) / Lecture 9 (Lektion)

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• Gametogenesis (Def) development of haploid sex cell in a diploid organism by meiosis includes: -oogenesis -Spermatogenesis
• Origin of gametes 4.Week of pregnancy PGC (primordial germ cells) arise in yolk sac 4. - 6. week: PGC migrate to genital ridge - this is dependent on interferon induced transmembrane proteins I and III  (IFITM1 & IFITM3)
• Male determing pathway: SRY SRY - sex determing region on Y-chromosome Function: Upregulation of SOX9 expression  SRY is expressed in both Sertoli cells and germ cells
• SOX9 - target of SRY SOX9 is a member of HMG-Box superfamily master regulator of Sertoli cell differentiation expressed in low levels in bipotential gonades, but persists only in testicular Sertoli cells
• General considerations: Epigenetic Regulation of gametogenesis some oocyte/sperm genes are differntly imprinted present imprinted marks must be erased gametes then need to be imprinted with the proper marks according to the sex of the developing embryo -> in somatic cells of this delevoping embryo the same imprinted marks must be retained (-beibehalten)
• Epigenetic changes in PGC genome-wide demethylation (reaching "ground state") remethylation occurs later during fetal life
• X-Chromosome re-activation in females PGC (2n) 2 X Chromosomes are acitve (inactivated X is reactivated) Reduction of Xist RNA levels
• Timing of gametogenesis Males:  Start: Puberty End : - (continues throughout adult life) Females: Start: during embryonic life  End: for each particular oocyte after fertilization [Menopause]
• Stops in Oogenesis 1. Stop: Meiosis I (prophase I, diplotene) ---> till puberty 2. Stop: Meiosis II (metaphase II) ---> until fertilization
• Periods of Oogenesis Proliferation Growth Maturation
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• Proliferation Period ~3rd month of embryonic development PGC --> Oogonia (2n)  primary oogonia become secondary oogonia
• Growth period 4 - 6 month of embryonic development secondary oogonia become Primary oocytes
• Maturation period 7-8 month of embryonic development Leptoten,Zygotene,Pachytene,Diplotene and Stop one oocyte finishes Meiosis I and develops in:  -one oocyte II (n) which continues with meiosis II and stops in metaphase II -one first polar body (n) Oocyte I grows to a large size 
• Ammount of Primary oocytes at birth ~700.000 primary oocytes remain in diplotene till puberty, rest of primary oocytes degenerates
• Ammount of Primary oocytes at puberty ~400.000 primary oocytes embryonic follicles -> primary follicles Maturation of primary oocytes 
• Oocyte: Structure Plasmatic membrane Nucleus Cytoplasm
• What happens in puberty (females) every month 5-15 oocytes I start maturation only one mature  primary follicles become secondary follicles (developing follicles)
• Secondary (developing) follicle develop from primary follicle several layers of follicular cells Anthrum enlarges
• Mature follicle (Graafian follicle) develop from secondary follicle Differentiation of follicular cells occur: -Corona radiata -Cumulus oophorus
• Cytokinesis (Oogenesis) unequal, but complete  -one large cell: oocyte II (n) -one small cell: polar body (n) 
• Regulation of Meiosis in oogenesis controlled by MPF (maturation promoting factor [composed of Cdc2 + Cyclin B] MPF induces: -chromosome condensation -nuclear envelope breakdown -formation of spindle Then, activation of Anaphase promoting complex B and decrease in MPF levels Mos protein kinase mainatins metaphase II arrest by inhibiting anaphase promoting complex.
• After fertilization... Oocyte II continues meiosis II one large cell: mature oocyte II (egg) one small cell: polar body (n)
• In Absence of fertilization Oocyte II stays in meiosis II, metaphase II Mature follicle shrinks promotion for the development of the next oocyte 450-500 mature oocyte II in one female life 
• Function: Granulosa cells: produce sex hormones react to different hormones produce different growth factors
• Function: theca cells Interna: produce hormons externa: connective tissue
• Function of polar bodies reduce chromosome number donate cytoplasm to oocyte II
• Spermatogenesis (Start-End) Start at puberty, continues through life time 
• Spermatogenesis Cycle Duration 64-72 days
• Sertoli cells, function surround developing sperm cells secrete proteins and fluids trophic function secrete growth factors synchronize events of spermatogenesis
• Spermatogenesis, periods Proliferation Growth  Maturation Spermiogenesis
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• Proliferation period, spermatogenesis begins in embryonic life, continues through life time PGC -> primary Spermatogonia Primary spermatogonia -> secondary spermatogonia
• Growth period, spermatogenesis begins in puberty secondary spermatogonia -> primary spermatocytes weak compared to oogenesis
• Maturation period, spermiogenesis two meiosis 22-24 days
• Spermatogonial syncytium Sinchronize spermatogenesis in one seminiferous tubule cells stick together
• Role of syncytium Akap82 protein - important in tail formation Akap82 gene is located on X-chromosome
• Cytokinesis, Spermatogenesis equal, but incomplete -sex cell precursors remain joined by cytoplasmic bridges (Syncytium)
• Spermiogenesis STEPS: Formation of Acrosome Nuclear morphogenesis Formation of tail structure Rearrangement of organelles Sheding most of the cytoplasm
• Function of Sperm deliver set of genes activate the egg
• Abnormal sperm and sperm production syndromes Teratozoospermia: a lot of abnormal sperm cells in ejaculate Azoospermia: no sperm in ejaculate Oligozoospermia: low sperm count (< 20 Mio / ml ejaculate) Sertoli cell only Syndrome: in seminiferous tubules only Sertoli cells  Kartegener Syndrome: motality of spermatozoa flagella is affected 
• Acrosomal reaction Acrosome => exocytosis, digestive enzymes are released into the Zona pellucida
• Sperm-Egg: recognition & binding sperm migrates through corona radiata sperm binds to a receptor molecule at Zona pellucida  -ZP1,ZP2,ZP3 (sperm-specific egg bindin) receptors plasma membrane of egg and sperm fuses => sperm cell enters binding leads to an increase in Ca2+which is a signal to complete meiosis II [Oocyte ofc]
• Cortical reaction corticular granules release enzyme => Zona pellucida hardens polispermy gets blocked
• Cleavage (regarding sperm-egg) series of mitotic divisions and cytokinesis that transform the zygote
• Significance of fertilization diploid chromosome number mixing paternal and maternal chromosomes

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