S100: Gametogenesis and Fertilization!Main Ideas!- Sexual reproduction is advantageous evolutionarily because it makes individuals w/novel genetic combinations and provides an efficient way to eliminate harmful mutations.!- Haploid gametes are made by meiosis, where 2 successive cell divisions follow one round of DNA replication.!- Sperm are small, compact cells highly specialized for fertilization of an ovum.!- Spermatogonia only begin to enter meiosis and produce spermatocytes and sperm after puberty.!- Each diploid primary spermatocyte gives ride to 4 mature haploid sperm, takes 64 days.!- Oocytes develop from primordial germ cells that migrate into the developing gonad, where they become oogonia!- After a period of mitotic division, they begin meiosis I and are called primary oocytes!- Primary oocytes stay arrested in prophase I for years, during which they grow, syn. a ZP (zona pellucida), and accumulate ribosomes, mRNAs, tRNAs, and proteins, using nutrients from the surrounding granulosa cells.!- In response to FSH and LH, the oocyte is stimulated to ovulate and completes meiosis I to form a small polar body and a mature oocyte, which proceeds to metaphase of meiosis II.!- The oocyte arrests there till fertilization, which signals the ovum to complete meiosis and begin embryonic development.!- Human fertilization begins when a sperrm, which has go thru capacitation in the female genital tract, binds to the ZP!- Binding of the sperm to the ovum induces the sperm to undergo an acrosome rxn, releasing proteases that enable it to penetrate the ZP!- The fusion of the sperm w/the ovum elicits a Ca2+ wave that activate the ovum, which causes the cortical rxn and the development of the zygote.!- Development occurs after the contents of the 2 pronuclei come together and their chromosomes align on the mitotic spindle, which initiates the first mitotic division. - Machinery of sexual reproduction is elaborate and many resources spent on it!in wild, only fittest and handsomest males get to reproduce!- Advantages of sexual reproduction!- genetic variation!- novel genetic combos, reshuffling genes helps species survive in an unpredictable envi!- elimination of deleterious genes!- stringest selection for fit/handsome males means good genes are transmitted and bad are more efficiently lost!- Sexual reproduction req. haploid gametes - Meiosis: 1 round of DNA syn, 2 successive cell divisions w/chromatid separation!- Timing, onset, and duration of meiosis= sexually dimorphic= diff. for the 2 sexes!- Females: meiosis I occurs in utero, at pub some complete meiosis I every month, fertilization --> completion of meiosis II!- Males: new cells enter meiosis continually after puberty, takes 64 days!- Retinoic Acid (RA) regulates the timing of entry into meiosis I - RA binds to RAR (retinoic acid R), a nuclear R!- in embryonic ovary: high levels of RA --> induce proliferating germ-line cells to enter meiosis at about 11/12 weeks!- in embryonic testis: Sertoli cells make an enzyme (Cyp26b1) that metabolizes RA, after puberty levels of that enzyme decrease --> RA levels can rise and meiosis resumes!- Gametes are highly specialized!- Sperm: small, motile (flagellum), streamlined for efficiency/speed (condensed DNA, no orgs except mitochondia, little cytoplasm), highly competitive envi - Ovum: large, nonmotile, lots of materials to support embryo growth (proteins, ribosomes, tRNAs, mRNAs, morphogenic factors, protective features), she's the only one!!- Hypothalamic-Pituitary-Gonadal Axis regulates ovarian and testicular development!- Kisspeptin= key reg. of puberty onset, binds to a GPCR!- GnRH= gonadotropin releasing hormone, a small peptide released by hypothalamus that signals the release of gonadotropins FSH (follicle stimulating hormone) and LH (luteinizing hormone) from pituitary!!- Modification of a germ cell to become sperm - Acrosomal vesicle: contains hydrolytic enzymes that help sperm penetrate ovum's outer coat!- DNA tightly condenses by protamines and sperm-specific histones!- Sperm are syn. in seminiferous tubules!- Sertoli cells: nurse cells for sperm!- secrete anti-Mullerian hormone (AMH) to send developing gonad down male pathway!- convert testosterone to estradoil to help w/spermatogenesis!- form the testis-blood barrier!- after puberty: secrete inhibins and activins (TGFB signaling pathway), reg. FSH secretion!- Leydig cells: interstitial cells!- make testosterone in response to LH!- Mature sperm travel to the epididymus, where they're stored and undergo more maturation, not ready to fertilize until they go thru capacitation!- Sperm capacitation is req. for fertilization = the set of physio changes that sperm must undergo in the female reproductive tract to become competent to fertilize the ovum!- prepares sperm for acrosome rxn and allows sperm to become hyperactive!- happens in ampulla, takes 5-6 hours!- involves poorly understood mech's in mammals!- in vitro: req. albumin, Ca2+, HCO3-!- albumin protein from female helps extract Ch from sperm membrane --> increases ability ofmembrane to fuse w/acrosome during acrosome rxn!- needs to be change in membrane potential where K+ leaves sperm and Ca2+ and HCO3- activate a soluble adenyly cyclase to increase cAMP --> tyrosine P of proteins incl. those needed to hyperactivate sperm and for sperm-ovum fusion!- after: sperm can find and bind ovum!- Human Oocyte Structure!- Oocyte: a developing egg/ovum that can't bind sperm or be fertilized!- Ovum= egg= mature oocyte: can bind sperm and be fertilized, second meiotic metaphase!- Corona radiata: layer of cells that provide proteins and nutrients to ovum!- Zona pellucida: a glycoprotein membrane that surrounds the pm of the oocyte and serves as a protective layer, a protein in the ZP (ZP2) is a binding protein for sperm and induces the acrosome rxn= rxn that occurs in response to sperm-ovum fusion which releases the enzymes from the sperm that can digest the ovum's tough coat!!!!!!!!!!- Maturing Oocyte Prepares for Development that occurs prior implantation!- meiotic divisions conserve the cytoplasm because the oocyte doesn't really divide (unlike spermatocytes0!- most of the growth happens in the primary oocyte (when the cells are bivalent) so there's 2x as much DNA for RNA syn.!- somes genes (like rRNA genes) become amplified --> can be a burst of protein syn. after fertilization!- follicle cells (corona radiata cells) link to the occyte thru gap junctions to provide precursors for
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