17.7212.11.06Human DevelopmentModelorganismsAnalysis PrinciplesNervousSystemHuman issuesCloningStemcellsOrganFormationFoundations+ +Developmental Readout3DstructurePostionalinformation21. Human embryogenesis2. Fertilization3. Fertility and teratogens4. ART5. Prenatal diagnosis6. Stem Cells1. Human embryogenesis3Early human development1Gilbert Figure 11.41Human embryoInner cell mass24Gilbert Figure 11.33(1) Amnion Structure and CellMovements During Human Gastrulation3Gilbert Figure 11.33(2) Amnion Structure and CellMovements During Human Gastrulation455Gilbert 21.10 Periods and degrees of sensitivity ofembryonic organs to teratogens662. FertilizationHeadNucleusAcrosome-from Golgi-proteolytic enzymesTail-flagellum-microtubulesMidpiece-mitochondria-energy77mammalian egg at fertilization8Zona glycoproteins are crucial for sperm bindingSperm binds ZP3then ZP2in zona pellucida of egg98Events leading to egg and sperm plasma membrane fusion in mammals10Fertilization animation: sperm/egg interaction and acrosome reactionCrazy little thing called love/ Queen 119Acrosome reaction: Limulus (horseshoe crab)(courtesy Prof. Paul Matsudaira MIT)nucleusacrosomal vesicleunpolymerizedactinpolymerizedactinacrosomal contents12Sperm entry into egg (hamster) 1310Wave of Calcium Release across Sea Urchin EggsDuring Fertilization Site of sperm entry123 430 sec14 signal transductionand consequences ofsperm/egg fusionfusion of pronucleimetabolic activation1511Slow block to polyspermy via cortical granule exocytosis16Slow block to polyspermy via cortical granule exocytosis II1712Slow block to polyspermy in frogs:raising the vitelline membrane (= zona pellucida)18Pronuclear Movements During Human FertilizationDNA = blue19133. Fertility and teratogensGilbert 21.10 Periods and degrees of sensitivity ofembryonic organs to teratogens614Gilbert 21.16 Bisphenol A causes meiotic defects inmaturing oocytes20Gilbert 21.18 Seminiferous tubules from control rat (A) and arat (B) whose grandfather’s mother had been injected withvinclozolin21153. Assisted Reproductive Technology(ART)Attention MIT students!!!Sperm donors neededMust be over 21$75 per donationEarn $900 per month!Call (XXX) XXX-XXX16Seeking egg donorDark haired MIT student 5’4” - 5’9” , 21- 29 years oldGPA at least 4.5 $65,000Minor surgical procedure Confidential contact (XXX)XXX-XXX spermatogenesisContinual mitosis, all meiotic products > sperm~108 per ejaculate, 1012-1013 lifetime2217oogenesisMitosis ends before birth, ~5x105 primary oocytes, 5,000 secondary oocytes <500 eggs mature lifetime!egg23Endocrine systemproduces hormonesthat regulategametogenesis2418Hormonal controlof spermatogenesisLH= luteinizing hormoneFSH = follicle stimulating hormoneGnRH = gonadotropin releasing hormone25Hormonal control ofegg productionExtra estrogen/progesterone = Birth control pillLH= luteinizing hormoneFSH = follicle stimulating hormoneGnRH = gonadotropin releasing hormone2619Extra GnRHand LH/FSH foregg donationHormonal control ofegg production27In vitro fertilization (IVF) procedure2820ART procedures29Olson et al, 2005Why are birth defects more prevalent after IVF? Health of parents?IVF procedures (ovulation, freezing embryos, culture)?3021Development and the mediaOrigin of loveHedwig and the Angry InchStephen Trask/John Cameron MitchellAfter Aristophanes, as interpreted by PlatoThank-you, Sylvain22 Br J Dermatol. 1991 Feb;124(2):146-51. Related Articles, Links Seasonal changes in human hair growth. Randall VA, Ebling FJ. Department of Biomedical Sciences, University of Bradford, U.K. Various parameters of hair growth were determined every 28 days for 18 months in 14 healthy Caucasian men aged 18-39. The number of shed hairs reached a peak around August/September. At this time the average loss of hairs was about 60 per day, more than double that during the preceding winter. The rate of growth of the beard was lowest in January and February and increased steadily from March to July to reach a peak about 60% above the winter level. The rate of growth of thigh hair showed a similar pattern though with less pronounced di!erences. No seasonal fluctuations in finger- or toenail growth were detected.Je!David235. Prenatal genetic diagnosis3116-19 weeks8-10 weeks24Sermon et al, 2004Biopsy for preimplantation genetic diagnosis (PGD)32PGD: Fluorescence in situ hybridization (FISH) with chromosome-specific DNA probesembryo 1embryo 2embryo 3 embryo 4Y212121XXXTrisomy 21 (Down’s)XYXX33256. Human stem cell issuesRobin, Paul and classIssuesEthicsUse of human embryosSource of eggs/ surrogate mothersFate of abnormal babiesMethodsHow to clone primates?ES cells >> eggs How to reprogram adult nucleiGene