Basis of Embryology 504-381A 2024 PDF

Basis of Embryology 504-381A 4 September 2024 Making germ cells  Making germ cells 1. Where do the germ cells come from? specification of PGCs? 2. What determines whether they wil...

Basis of Embryology 504-381A 4 September 2024 Making germ cells  Making germ cells 1. Where do the germ cells come from? specification of PGCs? 2. What determines whether they will become oocytes or sperm? 3. What controls entry into meiosis? 3 main topics -where the germ cells come from -what determie=nes if germ cells becomes oocytes or sperm.  Primordial germ cells PGC Primordial germ cells what are PGCs? -cells that give rise Oogonia Spermatogonia to gametes in vertebrates. theyre precuroses to the gametes Oocytes gametes Spermatocytes in XY indiv the PGC will become sperm. it depends on the env the cell finds itself in., it has no preference to choose if it becomesooogonia or sperm it rlly just deoends on the env. pgcs have no inherent preference  Are the germ cells fundamentally different from the somatic cells? Yes egg germ germ Infinite life are pgc like any other cell? soma basicall soma Finite 0we might think that life PGCs are different than somatic cells GERM CELLS VS y the bcs theyre kind of infinitr cells as they give ris to germ SOMATIC CELLS whole cells , the egg and life. body if they are fundementally different, the model follows that both cells types separate and the pgcs will have their infinite life and the somatic cells eventually die.so the somatic cells would be liek the house for the gemr cells for No egg soma them to propagate indefinetly. if theyre not fundmentally different well germ cells will make the gametes n other cells types. mammals follow this model. the main thing is that the PGCS WILL BE SEGRAGATED FROM THE SOMATIC CELLS (called specification of PGCS). the egg gives rise to abunch of germ soma cells with a portion of them become germ cell, s  nematode Are the germ cells fundamentally different -all chromatin is retained in germ cells, which is very different from somatic from the somatic cells? cells, that degrade some of it. (degradation of chromatin in somatic cells only) in flies, in early dev in the embryo thres a cluster of cells that become Nematode segregated in the posterior pole and theyre descendents from the pgcs, (Ascaris) theyre very separated from the rest of the cells of the fly. (segragation of Certain regions of chromatin degraded in somatic cells; PGCs, to posterior pole) All chromatin retained in germ cells worms: in unfertilized egg there r aggregates of mitochondria the red dots become clustered into cells which become germ cells so here AS WELL THE PGC ARE SGERATED THIS IS Fly THE MP I THINK (segragation of PGCs) (Drosophila) Pole cells segregated at posterior end of embryo (pole plasm) contain germ cell determinants Worm (C. elegans) Aggregates of mitochondria, protein and RNA in egg (P-granules) become segregated to germ cells  What about mammals? Lessons from monozygotic siblings and embryo biopsies IN TWINS N TRIPLETS, IN EARLY EMBRYOGENESIS somatic vs germ (where there are like 30 CELLS) cells why the model of worms doesnt apply to mammals. -the cell separates and each fragments becomes an embryo (hence twins come from same cell that). the argument against the model of yes, is that we dont have cases where the embryo doesnt get germ cells. when this happens, if it were the worm model, one of the fragments would get germ cells while the other doesnt, for humans this doesnt happen, the germ cells will separate X and privde each embryo with an egg or spem. another argument against the model: in vitro fertilzation serves to genetically test embryos to see that it doesnt carry a bad gene disons--done by taking a cell of the embryo n do agenetic analysis. lets say u get a cell and that cell that is the pre-cursors to the germ cells, that means that that baby wont have germ cells n be bale to have egg/sperm, these cases dont happen.  Overview of differentiation of the primordial germ cells (PGCs) - mouse Stage of embryogenesis Event Key genes 3 weeks of gestation./pregnancy. notation of E6.5: embryo is 6.5 days old. 1.some cells in embryo become determined to become pgc , their cell fate is assigned- specification. 2. once assigned a fate as pgc they have to migrate into developping gonads. 3. events of sex det. Origin and specification of the primordial germ cells  Anatomy of the embryo at PGC specification - mouse what is PGC specification -pgc spec. induces germline. -specification is the process by which the PGCs will be set aside to actually become PGCs meaning the precursors of the gametes. VE: visceral endoderm cells of the rope fro placenta, AVE: anterior visceral endoderm pink cells (anterior epiblast cells) form the embryo. left hand side is for the head and right hand is for tail. the embryo at this stage has a clear ant./post angle.  Anatomy of the embryo at PGC specification – mouse vs human on the other hand there is a linear arrangemnt in human for epiblast cells which are the cells pink: cells that form the that wil form the futur foetus (pink mouse, they form the cells). embryo (futur foetus) , the PGCs arise from tail end--> called epiblast posterior epiblast. what does the embryo look like once the PGC undergo specification, moiuse vs humans? in mouse the epblast cells are in a circular arrangemnt while humans will have their epibast organized in a linear fashion and having the pGCs arise from the posterior end of that line of epiblast. VE: visceral endoderm CT: cytotrophoblast AVE: anterior visceral endoderm SCT: syncytiotrophoblast EPI: epiblast (future fetus) YSE: yolk sac endoderm ExE: extraembryonic ectoderm what is the positon of newly Anatomical position of newly specified PGCs specified PGCs. humans might have two locations for the origin of PGCs, while mice only have one origin (not to know the two locations) -both in mice in the mesoderm ish. in humans the position of newly PGCs seem to be in b/w the blast cells (epi and hypoblast) towards the posterior side. pgc arise -two origins: its quite uncertain, mouse vs human pas a savoir, mais savoir that pgc arise from posterior end of embryo. why not at anterior or middle?  location of origin of Why do the PGCs arise in the posterior epiblast? PGCs? and why do they arise from it. -PGCs arise from the posterior epiblast bcs the environment of that Transplantation experiments location is what gives them that cell fate. if PGCs were placed at the distal tip indtead, then Cells from distal tip of epiblast, which normally give rise to neuroectoderm, when theu cell fate would be transplanted to posterior epiblast, can give rise to PGCs neurpectoderm cells a transplantation experiment; instead. the posterior epiblast is the location where the primordial why not at anterior or middle? for the arisal of germ cells arise from. the PGCs in the epiblast layer. even cells from the distal tip of epiblast when placed in the -experimentation through tranplants helped posterior epiblast will become determined the definite location for PGC arisal. PGCs. transplant a type of cells into new position, these transplanted cells acquired the fate of their new position. hence the position of the cells in this stage of dev will dtermine thaat they become PGCs (the environment is what detrmine the cell fate of cells in this stage of dvelompment, no other thing). the experiemnt consisted of ranplsatig cells of the distal tip of epiblast to the posterior epiblast, this made them go fom making neuroectoderm cells to PGCs. Cell signaling pathways important in PGC specification: Wnt two signaling pathwyas important PGC specification: WNT explain cell and TGFBETA. signaling pathway of WNT, when its WNT signalling A) WNT signaling: name comes form the ligand being present/absent. encoded by genes called wnt. WNT regulates gene transcription through stabilizing beta- catenin. 1.absence of WNT: beta-CATENIN IS MADE BY CELL BUT IF NO SIGNAL IT GETS BOUNDED BY SOME PRTS N GETS DEGRADED (hence doesnt do much). so WNT doesn't activate the making of b-catenin rather it prevents its degradation. 2.presence of WNT: iWNT activates its receptor on cell surface (extracell. rec.) called FRIZZLE, it activates intracellular signaling pthwy which dissassembles the complex around b-catenin and makes beta-catenin explain the WNT signaling pathway stabilized. NOW, stable beta-cat will go to nucleus n that leads to PGC specification/ activate transctiption of target genes -PGC will be specififed, meaning when theyre set aside from other cells and become the progenitor of the gametes. WNT seems to be the ligand binding to the LRP recpetor. WNT Eisenmann Wormbook chatgtp (WINGLESS,INTEGRATIVE proteins) will work in the process of migration and peoliferation of PGCs by guiding the PGCs in early development to the developping gonads.  Cell signaling pathways important in PGC specification: Transforming growth factor beta WNT signalling TGFβ signalling explain the role of the TGFbeta signaling pathway in PGC specification? BMP: bone morphogenetic protein what is BMP? BMP stands for bone morphogenetic protein, its used in the signaling 2nd pathway pathway important B) TGFBETA aignlaing; for PGC tgfbeta ligand binds to receptor on membran (extracell. rec) specificatrion n it activates a signaling pathwy involving many proteins like smad2/3 or smadsEisenmann 5.8 (by BMPWormbook ligand -of tgfBETA FAMILY- on different receptor, pas a savoir) these SMADs Zhao et al Int J Biol Sci 2018; get translocated to nucleus where they r stabilized n they 14:111-123. doi:10.7150/ijbs.23230 activate specific set of genes, different than those activated by the WNT pathway. Importance of Wnts and BMPs (TGFβ family) in specifying the PGCs the WNT and TGFBETA/ BMP pathway tell the cells in the posterior epiblast to become PGCs distinguish the role of WNTs and ligands for tgfbeta BMPs in the specification of pthwy. bmp4 is PGCs? made by the -is their location important.. extraembryonic ectoderm cells n acts on the epiblasts cells for gene transcrption. where germ cells arises- posterior epiblast Tam & Loebel (2009) Cell 137, 398  Specification of the primordial germ cells: Key genes these genes are what are some genes inside the cells (PGCs) to allow Ifitm3/Fragilis Transmembrane protein/viral entry not only important them to become PGCs; for germ cells but also for other cells. these might be activated by either the wnt or tgfbeta. les Dppa3/Stella Uncertain TRANSCRIPTION names sont pas a se some genes rappeler. most of them are important in PGC FACTORS but dk if theyre repressor or transcription factors, but wre specification. Prdm1/Blimp1 DNA-binding transcriptional activators. regulator not sure if theyre activators or repressors. Prdm14 DNA-binding transcriptional regulator Tcfap2c (AP2γ) DNA-binding transcriptional regulator what determines if Differentiation of the primordial germ cells: PGC becomes oocyte or sperm? demethylation of DNA how does demthylation cntribute to the differentiation of PGCs? -methylation is a modifcatiin on fna and chromatin which has a but of contorlling gene expression and protein  DNA methylation: modification of cytosine within chromatin methylation of this methyl grp in C5 of cytosine. -occurs 5’ATACGGACTGCCGAAT for only certain but lets say there is an modification of cytosine (in 5-3 enzyme that likes to add Cytosine cytosine direction creo). 3’TATGCCTGACGGCTTA Methyl grps to cytos only when a residing oppsited to cytosine is only one strand of Methylated cytosines adjacent to a the DNA gets a M guanine is when its cytosone. cell 1 susceptible to methylation. structure of cytosine in the methylated state of cytosine, it makes its complement propagation easier onto new ary strands. cell 2 what occurs during L side is cells during cell division. dna methylation methylated. -there is a modification of both daughter cells cytosines within the have the same chromatin, methylation as the mothet celell  DNA methylation: can be transmitted after DNA replication and therefore is a heritable during cell proliferation is methylation heritable? dna methylation can be transmitted after dna replication. M of opposing cyto on the opp strand  DNA methylation of gene promoters is linked to repression of gene expression what occurs when gene promoters are methylated? methylation of gene promoters will lead to the Methylaytion is associated to gene expression dk how rlly. repression of gene -in the promoter region of some genes, there is high expression. density of CG residues (white sticks with white circles). the state of M of dna , The dna is UNmethylated in promoter regions OF GENES THAT ARE EXPRESSED. so demethyl is associated to the activation of gene expression.  DNA in PGCs becomes demethylated MP: once pgc have been specified theure dna becomes demthylated (demthyl of cytosines at the 5th carbon) graph showing that basically, the fct of demethyl. is to PGC dna gets return chromatin to ground state for demethylated--> cells to be in undifferenciated state, no this leads to the bias, not trying to become cell types, this differentiation of allows them to become anything--> PGCs. gives germ cells totipotency. DNA demethylation may help give germ cells ‘totipotency’ what is totipotency? a totipotent cell can give rise to a whole organism, an Cell type 1 exaple is the zygote. this includes the formation of embryonic (cells of body) and extraembryonic tissues here are different (e.g. placenta) cells types having Cell type 2 different cytosines methylated Cell type 3 PGC PGC precursor Totipotent germ cell after demtylation PGCs will have a low level of methylation hence now they have a clean slate and can become anything so basically this is the purpose of demthylation. Migration of the primordial germ cells  How do the germ cells migrate from their site of origin to the developing genital ridges? mp: PGC originate at the posterior epiblast and migrate to the developping gential ridge through an acive migration. this slide is not to know in posterior epiblast how PGC will migrate from site of origin (im guesssing the posterior epiblast in humans ) to the developing genital ridges. -its at the genital ridges where sex detrminaton might occur? Saitou and Yamaji 2012  Overview of differentiation of the primordial germ cells (PGCs) - mouse Stage of embryogenesis Event Key genes  Sex determination and differentiation of the germ cells within the genital ridge genital ridge  Y chromosomes. sry is on the short arm of the y CHROMO. Biological sex determination in (most) mammals sry was discovered in mice. an XX mice carrying the sry gene is enough for them to be phenotypically males but not make sperm ‘Ancient’ Position in the uterus Sperm from left (girl) or right (boy) testis X Y Higher (boy) or lower (girl) temperature of uterine environment Late 19th C Discovery of chromosomes 1959 Turner syndrome – XO females theories of the fate of germ cells depends on phenotypic cells assumed Klinefelter syndrome – XXY males by embryo. temp. of uterus would detetrmine embryo girl or boy. late 19th: chromos discovered. 1952 1990 peeps that have turners syndrome Human SRY discovered will have 1x X and no second sex – part of Y present in XX males chrosmomes-they are females. klinefelter: have two Xs and 1xY, they r Mouse Sry discovered males. so this gave us that Y – also on Y-chromosome chromsome is resp for males sex detrmination. PAR = pseudo-autosomal region most genes on the Y chromo is for MSY = male-specific Y XX mice carrying Sry develop as males regulation of spermatogeneis. SRY is the important one.  The genetic basis of (most) mammalian biological sex determination Y-chromosome lets say male not making 6 different cases. sperm,discoverd that males has two Xs in all 6 cases there chromsomes with small portion of Y was a region that chromo translocated into X chromo and allowed for the Portion of Y-chr translocated onto male detrmining they were phenotypically males. -so they started to wonder what aprt of X-chr in different phenotypic males genes. the Y chromo translocated inot the X having XX genotype chromosm, all those 6 cases had to hvae one portion in common which allowed these 6 people to be henotypically males. Male-determining gene must be within this region cs thats the portion that all 6 chromosomes had in common. so SRY gene should be there.  Structure of the SRY / Sry gene and protein what does SRY do to DNA? prot SRY can bind to dna with a specificifty to certain sequences. Most structure of sry importantly SRY will bend DNA but protein in some what is the SRY gene? why does this bending of dna by SRY animals. -the Sex-determining prot. help in detrming sex Region Y is a gene region determination??? on the Y chromo that determines male sex. rich in glutamine region in sry protien in mice.,  The crucial role of SRY sex determination is done through the expression of the SOMATIC cells of the genital ridge to explain role of SRY, lets observe when its SRY protein. expressed vs when its not... so what determines if ur a sry expressed: male is the expression or SRY expressed or SRY not expressed sertoli cells express some sertoli genes n they not of SRY---> this sox9 (dep on expression tell other cells in gonads to develop into leydig indirectly shoes that of sry n sox9) cells or pre-leydig cells (the two principle GERM cells are not required to give the testes Differentiation of Differentiation of somatic cells in testes-both triggered by sry or ovaries. Sertoli cells pre-granulosa cellsthen sox9) leydig produce testosterone-- makes male secondary sex differantiation. + what i understand: once there is sexual SRY not expressed: differentiation (meaning there will be the differentiation of pre- once we know that the Differentiation of Differentiation of granulosa which are cells that nourrish organisms has either Leydig cells pre-theca cells oocytes in ovary during growth n development testes or ovaries) then the there will be diff. of pre-theca cells and secondary sexual differentiation of females. + germ cells will playa role as the pre-cursors to sperm or ova. veyr important: Production of female secondary sexual germ cells r not required for differentation testosterone; differentiation into ovaries or testes, no matter of chromosomal consituion (either xx or xy) Male secondary sexual so germ cells dont play role in sex differentiation DETERMINATION. its the somatic cells, cs thats where sry is epxressed. Germ cells are NOT required for sexual differentiation of the gonad – and thus of the individual  How does SRY work? WHY DOES SOX9 MUT CAUSES SKELETAL ABNORMALITY IF ITS INVOLVED IN SEX DET.? do females have SOX9? and in what cells? how does SOX9 act in other cells? well sox9 in gonads is essential for gonad to dev into testes but sox9 has other meaning not on functions in other cells, females have sox9 Sox9 Autosomal (human chr. 17) sex-chromosomes in other cells types (not in gonads ). sox9 is not active in somatic cells of (23) gonad in fems cs we dont have sry gene. DNA-binding protein (transcription factor) in other cells that are not somatic cells of XY gonads, sox9 will not need SRY for iyd activation. but in the genital ridge, sox9 does require SRY, in somatic Mutations cause severe skeletal cells of XY gonad. abnormalities, sex reversal in what types of cells is SRY gene (Campomelic dysplasia) expressed? fro how long is SRY gene expressed? wht happens after that. sry is expressed for a small period of time in somatic cells of XY gonads, so not expressed in other Genital Sox9 expression cells of embryo. like a day or two ridge requires SRY Sry is expressed in the fetal testis days expression of sry. and this is for only a brief period of time enough to trigger male development in mice. what type of feedback maintains sox9 Other tissues active?what if sox9 is inactive? hwo does SRY work? and cells sry turns on sox9 genes n sox9 feedbacks at the genital ridge, which is Sox9 expression where thr PGCs migrate to n it maintains its on expression (+ after theyre differentiated), does not require SRY feedback), sox9 drives the male changes SOX9 expression needs SRY, in somatic cells of XY gonads---- while in other tissues and cells there r other factor MAKES EMBRYO DEVELOPPED AS A SOX9 expression doesnt that turn on sox9 in MALE. require SRY. other cells if sox9 is NOT ACTIVATED THEN EMBRYO BECOMES FEMLAES.  Downstream of SOX9 why does it mean for gonads to be bipotential? what genes will activate in absence of SRY activation, n what occurs? gonad is bipotential cs gonad can go in either direction (ovarys or testes). in absence of sry: in somatic cells of gonad, wnt4 is activated, rspo1 enhnaces wnt singaling and these trigger ovarian devlopment n fem differantiation pathwy. presence sry: basically different set of genes leading to testicular development.  Biological sex determination – What about females? Many genetic interactions during sex determination R-spondins R-spondins enhancment of wnt Nuclear (active) Transcription of Wnt β-catenin target genes some important proteins/ what does WNT4 drive? what molecules for correct protein enhances its activation? femaale development wnt 4 is the ligand impo for female -R-spondin dev. -Wnt4; which is initially Wnt 4 Initially expressed in XX and XY drives development down the present on both XX and XY female side to make ovaries n fem but then becomes restricted Then becomes restricted to XX secondary sex characteristics. to XX (females) what occurs whn mutations of WNT 4 and Wnt 4 mutations R-spondins occurs? what does this prove? (inactivating) Partial female-to-male -partial female to male sex reversal occurs R-spondin mutations sex reversal for mutations in wnt4 and rspo1. (inactivating) -reinforces idea that wnt4 in those cells at that time is very important to female development (FEMLAE HUH NOT MALE CS WNT N RSPONDIN R FOR FEM DEVLOPMENT) Biological sex determination – summary some transcription factors IMPORTANT FOR FEM DEVELOPMENT TO MAKE OVARIES. Capel 2019 Reproduction  Primary sexual differentiation – morphological aspects XY germ cells clustering surrounded by futur sertoli cells the semeniferous tubules how are germ cells packaged/or look like morphologically in the early phases of development? XX germ cells remian individualized then become enclosed by granulosa cells , so each oocytes (which can becomes Ross and Capel Tr. Endocrinol. Metab. 16, 19 ovulated eventually) become enlcoses by the granulosa cells.  Development of germ cells within the gonad how do male n fem germ cells act how does development differ for differently? fem and males? PGCs arrive in genital ridge initally both start the same with in males the PGCs migratong to the after rounds of proliferation and its genital ridge where they undrrgo arrest, germ cells in testes stop some rounds of proliferation 2-3 rounds of cell proliferation mitotically until puberty. (2-3x), then there is an arrest on rpoliferation. from here, the fem side: PGCs will go inot meiosis for germ cells stop mititoc prolif but enter females, but male PGCs will go Proliferative arrest early events of meiosis like ---> into mitotic arrest until puberty. (occurs before birth) recomb b.w homo chromos, etc why do male n fem germ cells act MALE FEMALE differently ??? mitotic arrest and Mitotic arrest maintained Germ cells enter meiosis until puberty Why do male and female germ cells behave differently?  To enter or not enter meiosis: whtat is the STRA8 and DMC1 gene, What is the molecular basis? where are they found, male vs fem? what stimulates STRA8? -retinoic acid (its vitamin a , or closel related to it) Expression of ‘Stimulated by retinoic acid gene 8’ entering meiosis ; -stra8 gene is stim by retinoic acid, its principles (Stra8) correlates with entry into meiosis … -the expression of expressed in females and is required for fem germ cells to enter meiosis. the gene Stra8 -dmc1 is gene that is expressed in correlates with the meiotic cells. entry of meiosis of germ cells looking at rna of what can we conclude rom the expression str8 gene of dmc1 n stra8? dmc1 expression occurs during meiosis. its (Dmc1 is expressed found in fem. gonads buy not in males in meiotic cells) gonads (can be a bit but after) === tso we can conclude that the expression of stra8 and Dmc1 is a marker for the entry to meiosis of female germ cells male female stra8 is being turned on in fems n not in males REC8 SCP3 …and is required for germ cells to enter meiosis pas tres impo -rec8 not expres in cell thta lack in stra8 gene so stra8 is a marker of entry to meosisis but als required for meiosos.  agonist vs antagonist effect? same images as last slide. stra8 What turns on expression of Stra8? expressio seen in xxx. with retinoic acid rec. antagonist , there is no expression of stra8 even in fems where it should be expressed Retinoic acid what will turn on the expression of Stra8? RA intracellular pathway? retinoic acid (vitamin a , or retinol binds to its closel related to it) receptor (stra6) then -stra8 gene is stim by retinoic trasnforms into retinoic acid. acid RA which binds to its -stra8 vs stra6: pas a savoir la receptor (RXR) and diff. activates the transcrpiton retinol of target genes. tipo stra8 dehydrogenase which tells germ cells to enter meiosis. retinal dehydrogenase agonist of RAR (agonist stims activity) will turn on stra8 expression in males, en plus detre expressed ds les femmes gonads. retinoic acid turns on stra8, stra8 retinoic acid receptor; tells germ cells to enter meiosis. retinoid X receptor but hwy XX cells enter meiosos and why not males neter? retinoic acid response element Vilhais-Neto Curr Biol  Why don’t XY germ cells respond to environmental retinoic acid? but hwy XX cells enter meiosos and why not expression of cyp males neter? through embryonic cyp26b1 ressembles XY germ cells must nit dev. fem vs males some other protein, enter meiosis due to whichc one and why? something related to them Cyp26b1, which degrades not responding to retinoic retinoic acid is expressed in acid. -sertoli cells makes embryonic male gonads cyp26b1 and its expressed in embryonic male goands -cyp is initally exp and degrades reti acid. in both but then it -cyp is initally exp in both becomes resticted but then it becomes to males resticted to males (like Stra8 Scp3 WNT4 is but in females) Male germ cells enter meiosis what happens in males during embryogenesis in mice in absemce of cyp: lacking Cyp26b1 some other genes r XY germ cells will activated and in male mice not respond to germ cells enter meiosis retinoic acid, why? Cyp26b1 genotype Cyp26b1 genotype +/- -/- +/- -/-  Molecular control of entry into meiosis: summary summary slide, explain the ritnol is produced, RA might molecular entry of germ cells be procued ss well but cyp is into meiosis in male n females? beng made by sertoli cells which blocks effects of RA Females Males (well degrades it) henc germ cellsdont get signl to enter meiosos, mesonephros Retinol Retinol retnol mght come from mesonephros. what i think CYP26B1 is RA RA CYP26B1 Sertoli produced by sertoli and will go germ germ mitotic meiosis degreade retinol in cells cells arrest gonad the male gonads recall, for males theyre germ cells germ cells in XX willl go inot mitotic arrest until gonads will puberty, this is once the PGC have undergo meisosis proliferate in the genital ridge and instead. undergo proliferative arrest.  Biological sex determination not in exam XX XY female male what is gonochorism: this term describes individuals that were born either male or female and reproduce as the same sex they were born in. what is protogyny: describes peeps that were born female but reproduce as males. its a male-first-sequential-hemaphroditism. what is protoandry: describes when ur born male but later on, reproduce as female biderectional: is whne an indiviv can change sex many times, they usually start off as females (protogyny) simultaneous: whne an indiiv can produce both gamates of both sexes at same time or in a short period of time.  Sexual differentiation during embryogenesis WNT4, RSPO1 SRY, SOX9 presence or no of male hormone in differentiation of mullerian vs wolfian duct? u will developped two ducts, if nothing happens the wolfian duct generates and the mullerian diferentiates n gives risee to vagina, uterus, etc. if male hormones r present then opposite occurs. testotserone causes wolfian ducts to differerntiate n give rise to epididymis vas deferense n seminal vesicle AND triggers the degradation of the mullarian duct by AMH (anti milarian hromone). in bipotential gonad, meaning it can give rise to ovaris (through mullerian duct) or testes(through wolfian duct), starts by having have both ducts but one dissapears. Leon et al 2019  Rare patterns of sexual differentiation Gene Chrom. sex Effect of genetic modification Phenotype Characteristics SRY XY Do not initiate testis development Female ‘Streak’ ovaries, no functional germ cells mutation of SRY? phenotype, effect. cs nothing trurns on sox9 hence female. no tetses Mullerian duct derivatives so no testeroone hence no wolfian duct and no amh so mullarien duct forms without being No Wolffian duct derivatives degraded. XXSRY Initiate testis development as Male Small testes, no sperm embryos with SRY translocation. intiate tetstis : have wolfian ducts derivaties No Mullerian duct derivatives but no mullarien cs AMH is being made. but small tetsis n no sperm cs the only gene they have for male dveelomen tis sry, manque tout le Wolffian duct derivatives rest. MUTATION IN SOX9 IN xx? SOX9 XX No effect on ovarian differentiation Female ‘Campomelic dysplasia’ NO EFFECT ON OVARIAN DIFF. cs sox9 is downstream of sry. XY Do not initiate testis Female No functional germ cells development as embryos Mullerian duct derivatives No Wolffian duct derivatives WNT4 XX Lethal – partial or full ovary-to- mutation in testis reversal WNT4? cs wnt4 is in so many tissues.  muttaion on AR? its on X chromo. testosterone works with AR. Gene Chrom. sex Effect of genetic modification so since fems have two Xs , weird Phenotype Characteristics for XX to have homogenous mut for AR. if ar mut for XY they have androgen insensityvity; leydig pumps tetsoteorne but no AR hence leydig have no Androgen receptor feedback cs body thinks it has no testerone= no male stuff XX Very rare! (AR) (X-chromosome) but makes No functional germ cells XY Androgen insensitivity Female No Wolffian duct derivatives mutation in AMH anti-mull No Mullerian duct derivatives hromone - pr fr one X chromo but no other sex chromo - turners syndrome , most die at birth, if Anti-Mullerian hormone or vagina, XX Nothing obvious (human) they do theyreFemale short peeps. Fertile its receptor muations has not much effect on XX. XY tho will make XY Uterine development; XXX: no prob, cs two of the Xs become inactivated. Male Usually infertile, though in XXY: few sperms made, phentypic male n tend to be taller than avg uterus Undescended testes vitro fertilization possible Sex chromosomal aneuploidy XO Turner’s syndrome Female 99% die before birth No functional oocytes XXX Triple-X syndrome Female Fertile XXY Klinefelter’s syndrome Male Few/no functional sperm if mutated 5-alpha-reductase XY Cannot convert testosterone to Female at birth (SRD5A2) di-hydro-testosterone Male external genitalia form at puberty di-hydro testosterone is the super acive form of testo. (due to increased production of testosterone) not made hence look like fems bcs 5-alpha-reductase, but at puberty start forming male genitalia prolly due to increase prod at testosterone or thye become more Some individuals produce functional sperm sens to testo (hence no need of the hydro testo)  Making germ cells 1. Where do the germ cells come from? 2. What determines whether they will becomegonaldal oocytesenv. or sperm? 3. What controls entry into meiosis? for women its RA made by both embryos but degarded in males mebryos.