embryology -...

Embryology Embryology

GametogenesisGametogenesis

1.1.Embryology Embryology –– introductionintroduction

2.2.The molecular and genetic basis ofThe molecular and genetic basis of

embryonic development embryonic development

3.3.Sex cells (gametes) and gametogenesisSex cells (gametes) and gametogenesis

4.4.Male gametesMale gametes

5.5.Spermatogenesis and its regulationSpermatogenesis and its regulation

6.6.Female gametesFemale gametes

7.7.Oogenesis and its regulationOogenesis and its regulation

Prof. Dr. Nikolai LazarovProf. Dr. Nikolai Lazarov

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�� Human EmbryologyHuman Embryology

�� Medical EmbryologyMedical Embryology

�� prenatal developmentprenatal development –

280 days, 10 months::

�� embryonic periodembryonic period ((embryoembryo) )

– from fertilization to 8th week of development

• preembryonic period (early development) –

from the fertilization to 2nd week of gestation

• embryonic period

(late development) – from the 3rd week to the end of 2nd month

�� fetal periodfetal period ((fetusfetus) ) – from the 9th developmental week to the birth

�� postnatal developmentpostnatal development

EmbryologyEmbryology�� EmbryologyEmbryology ((Gr. Gr. έµβρυονέµβρυον, , embryo + embryo + logoslogos, , study)study)

� general embryologygeneral embryology (embryogenesis)� special embryologyspecial embryology (organogenesis)


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Basis of embryonic developmentBasis of embryonic development

� transcription factors– general and specific� zinc ring proteins

� homeodomain proteins

� signaling molecules• paracrine signaling

• juxtacrine signaling

� Wnt proteins

� hedgehog proteins

� transforming growth factor-beta

� fibroblast growth factor

� transmembrane receptors

� signal transduction pathways –first&second messengers

�� Molecular and genetic basis:Molecular and genetic basis:


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Sex cells (gametes)Sex cells (gametes)�� Reproductive tissueReproductive tissue::

� a separate tissue – A. Hadjiolov, 1930

� kind of epithelial tissue

�� composition:composition:

�� sex cellssex cells (gametesgametes) – male and female

�� ““somaticsomatic”” cellscells

�� embryonic origin:embryonic origin:� primordial germ cells (gonocytesgonocytes)

� formation in the epiblastepiblast –2nd week of gestation

�� movemovementment toto the wall of the yolk sacyolk sac – 3rd week

�� migrationmigration towardtoward the developing gonadsgonads – 5th week

� formation of

primary sex cordsprimary sex cords

�� sex differentiationsex differentiation –male and female

�� gametogenesisgametogenesis


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GametogenesisGametogenesis

�� cconversiononversion of germ cells into male and female gametes

�� the cell divisionthe cell division that takes place in the germ cells to generate male and female gametes is meiosisis meiosis

�� cytodifferentiationcytodifferentiation

�� forms of gametogenesisforms of gametogenesis::�� spermatogenesisspermatogenesis (male)

�� oogenesisoogenesis (female)

�� gametogenesis:gametogenesis:


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�� spermatocytopoiesisspermatocytopoiesis –in seminiferous tubules of the testis:

�� dividingdividing of spermatogonia bymitosis (spermatocytogenesis)(spermatocytogenesis)

�� growth and maturationgrowth and maturation by meiosismeiosis

�� cytodifferentiationcytodifferentiation of spermatids

into spermatozoa ((spermiogenesis)spermiogenesis)

�� spermatogoniumspermatogonium �� maturemature spermatozoonspermatozoon::

�� process durationprocess duration –– 64 64 daysdays

�� peculiarities of spermatogenesispeculiarities of spermatogenesis::� maturation of sperm begins at pubertybegins at puberty

�� wavywavy and and continuously continuously coursecourseto a ripe old ageto a ripe old age

�� twotwo meioticmeiotic divisionsdivisions withoutwithout interphaseinterphase

�� four mature spermatozoa are formed four mature spermatozoa are formed from one spermatogoniumfrom one spermatogonium

�� connected by connected by cytoplasmic bridgesbridges

�� oonly after thenly after theirir separatseparationion from the residual bodies from the residual bodies can the spermatozoa be considered isolated cellscan the spermatozoa be considered isolated cells

SpermatogenesisSpermatogenesis


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�� sustentacular cellssustentacular cells� derived from

the surface epithelium

� elongated pyramidal cells – 30-70 µm

�� CharcotCharcot--BBööttcher ttcher crystalscrystals

�� basalbasal and adluminaland adluminalcompartmentscompartments

�� occluding junctionsoccluding junctions ��

bloodblood--testistestis barrierbarrier

� main functions:functions:� support and protection of the

developing spermatozoa

� trophic (nutritional) role

� phagocytosis – residual bodies

� secretion (endocrine functionendocrine function) –inhibin, testis transferrin, androgen-binding protein (ABP), anti-Müllerian hormone (AMH)

� bind vitamin Е and А

NonNon--spermatogenic cellsspermatogenic cells

Enrico SertoliEnrico Sertoli

(1842(1842--1910)1910)

�� SertoliSertoli cells:cells:


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�� interstitial cells interstitial cells –– 18501850

�� formation during the formation during the fetal period fetal period ((during 16during 16thth

andand 2020thth weekweek ofof gestationgestation))

�� secondary interstitial secondary interstitial cell cell –– at pubertyat puberty

�� locatedlocated individually or in small groups around the capillaries

�� rounded or polygonalrounded or polygonal

�� wellwell--developed sERdeveloped sER

�� lipofuscinlipofuscin pigmentpigment

�� ReinkeReinke’’s crystalss crystals –– 33--20 20 µµmm

�� steroidsteroid--secreting cellssecreting cells ––

produceproduce androgens androgens (testosterone, (testosterone, androstenedione and androstenedione and dehydroepiandrosterone) dehydroepiandrosterone) �� secondary male sex characteristicssecondary male sex characteristics

NonNon--spermatogenic cellsspermatogenic cells�� LeydigLeydig cells:cells:

Franz von LeydigFranz von Leydig

(1821(1821--1908)1908)


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Spermatogenic cells

�� Primary spermatocytes:Primary spermatocytes:

�� largest cellslargest cells – 18-20 µm

� enter a prolonged prophaseprolonged prophase of first meiotic division (22 days) – preleptotene spermatocytespreleptotene spermatocytes

�� diploiddiploid – 4646 (44, XY) chromosomeschromosomes

� 23 tetrades (2n DNA2n DNA)

�� SpermatogoniaSpermatogonia (Gr. (Gr. sspermaperma, seed, seed + + gone,gone, generationgeneration)::

�� about 12 about 12 µµm in diameterm in diameter

�� situated next to thesituated next to thebasal lamina of the epitheliumbasal lamina of the epithelium

�� type Atype A –– stem cellsstem cells

�� type type AdAd cellscells –– divide rarelydivide rarely

�� type type ApAp cellscells –– mitotic divisionmitotic division

�� type B type B –– progenitor cellsprogenitor cells((mitotic divisionmitotic division – 16 days))


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Spermatogenic cells

�� Secondary spermatocytes:Secondary spermatocytes:

�� smaller cells smaller cells –– 12 12 µµmm

�� in meiosis II (16 days) in meiosis II (16 days) ––prespermatids prespermatids

�� haploidhaploid –– 23 chromosomes23 chromosomes

�� normal amount of DNA (2n)normal amount of DNA (2n)

�� Spermatids:Spermatids:

�� small cells small cells –– 77--8 8 µµmm

�� early spermatidsearly spermatids –– oval in shapeoval in shape

�� late spermatidslate spermatids –– elongatedelongated

�� juxtaluminal locationjuxtaluminal location

�� connected by cytoplasmic bridgesconnected by cytoplasmic bridges

�� haploidhaploid –– containcontain 2323 chromosomeschromosomes

�� reduced amount of DNAreduced amount of DNA –– 1n1n

�� do not dividedo not divide –– undergo spermiogenesisundergo spermiogenesis


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�� 3 phases3 phases::

�� GolgiGolgi phasephase

� proacrosomal granules

�� acrosomal phaseacrosomal phase

� acrosomal vesicle

� acrosome – hydrolytic enzymes:

• hyaluronidase

• neuraminidase

• acid phosphatase

• acrosin (zonalysin)

�� maturation phasematuration phase

� residual bodies are shed

� formation of spermatozoa

�� release of mature spermatozoarelease of mature spermatozoa �� spermiationspermiation

SpermiogenesisSpermiogenesis�� spermatidspermatid �� maturemature spermatozoonspermatozoon::

�� process durationprocess duration –– 224 4 daysdays


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�� LocalLocal regulationregulation – stimulatory and inhibitory:

�� SertoliSertoli cellscells – ABP and inhibin

�� LeydigLeydig cellscells – testosterone

�� Spermatogenesis regulating factorsSpermatogenesis regulating factors::

�� temperaturetemperature ~35°C (cryptorchidism)

� rich venous plexus, pampiniformpampiniform plexusplexus

�� evaporationevaporation of sweat of sweat from scrotumscrotum

�� contractioncontraction of cremaster muscles

�� malnutritionmalnutrition

�� alcoholismalcoholism

� action of certain toxic drugstoxic drugs

�� XX--ray irradiationray irradiation

�� disturbance in blood supplydisturbance in blood supply

Regulation of spermatogenesisRegulation of spermatogenesis

�� Central regulationCentral regulation �� stimulatorystimulatory influenceinfluence::

�� hypothalamushypothalamus –– GRH (hypophysis)

�� adenohypophysisadenohypophysis – FSH (seminiferous tubules)

LH (Leydig cells)


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�� structurestructure:�� headhead – length 5 µm; wide 3 µm; apex 1 µm

� condensed nucleus,nucleus, 1-2 vacuoles�� acrosomal capacrosomal cap

�� neckneck – length 0.3 µm; diameter 1 µm

� covered by plasmalemmaplasmalemma�� basal bodybasal body – proximal centriole

�� tailtail –– flagellumflagellum�� middlemiddle piecepiece – length 5-7 µm;

diameter ~1 µm•• axonemal complexaxonemal complex• spiraled mitochondriamitochondria

�� principal pieceprincipal piece – 45-50 µm• longitudinal and circumferential

fibrous sheath

�� end pieceend piece – 5-7 µm•• axonemeaxoneme• surrounding plasmalemmaplasmalemma

�� SpermatozoonSpermatozoon (Gr. (Gr. σπέρµασπέρµα, seed, seed + + ζῷονζῷον,, living beingliving being)::

�� mature male gametemature male gamete� first observed in 1677� total length length –– 58-67 µm

SpermatozoonSpermatozoon

Anton van Anton van LeeuwenhoekLeeuwenhoek

(1632(1632--1723)1723)


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Female gametesFemale gametes�� Female sex cells:Female sex cells:

�� oocytes oocytes ((Gr. Gr. oonoon, egg, egg + + kytoskytos))

�� follicular cellsfollicular cells� flat epithelial cellsepithelial cells�� defending functiondefending function�� secretory rolesecretory role –– liquor folliculiliquor folliculi�� endocrine secretionendocrine secretion –– estrogensestrogens� ovulation � lutein cellslutein cells – progesterone

�� thecal cells (thecocytes)thecal cells (thecocytes)�� build up the build up the theca internatheca interna�� steroidsteroid--secreting cellssecreting cells –– estrogensestrogens

� ovulation � luteinlutein cellscells – progesterone

�� interstitial cellsinterstitial cells� active thecal cells� in small groups throughout

the cortical stroma around vessels� source of ovarian androgens

�� hilus cellshilus cells� in ovarian medulla� similar to Leydig cells in testis� produce testosterone


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�� primary oocytesprimary oocytes:� medium-sized cells – 25-30 µm

�� prophaseprophase of the first meiotic division

�� diploiddiploid

�� secondary oocytes:secondary oocytes:� larger in size – 40-50 µm

� 2nd meiotic division (metaphase)

�� haploidhaploid – 23 chromosomes

� normal amount of DNA (2n)

�� ovumovum ((mature oocytemature oocyte):):� large cell – 50-150 µm� large nucleus with haploidhaploid numbernumber of chromosomesof chromosomes�� oolemmaoolemma with microvilli� acidophilic PAS-positive zona pellucidazona pellucida,

glycosaminoglycans, glycoproteins and sialic acid, source of fertilizine� perivitelline spaceperivitelline space

�� oogoniaoogonia – mitotically active cells

� reduction in number – cell death� primordial follicles

OocytesOocytes


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�� prenatal stageprenatal stage:

�� period of proliferationperiod of proliferation –– gonocytesgonocytes

�� oogoniaoogonia –– 7 7 million/5million/5thth monthmonth

�� primary oocytesprimary oocytes –700000700000--2 2 millionmillion

�� postnatal stage:postnatal stage:

�� growthgrowth –– primary oocytesprimary oocytes

� remain in prophase of meiosis I(diplotene stage)

�� oocyte maturation inhibitoroocyte maturation inhibitor

�� maturationmaturation –– secondary oocytessecondary oocytes

�� peculiarities of oogenesispeculiarities of oogenesis:� first meiotic division (meiosis I) begins during fetal life

and is completed just before ovulation � meiosis II is completed only if the oocyte is fertilized� one mature oocyte (ovum) and three polar bodies are

formed from one oogonium� different structural peculiarities in different animal

species

OogenesisOogenesis�� oogoniaoogonia �� maturemature oocytes (ova)oocytes (ova)::

�� in female gonadsin female gonads –– ovariesovaries


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�� primordial follicleprimordial follicle�� primary oocyteprimary oocyte�� flattened follicular cellsflattened follicular cells ((single layersingle layer))

�� primaryprimary folliclefollicle – 35-40 µm

�� primary oocyteprimary oocyte – 25-30 µm

�� cuboidal follicular cellscuboidal follicular cells

�� secondary folliclesecondary follicle(growing(growing or or antral)antral)– 0.2 mm

�� primary oocyteprimary oocyte (50-80 µm)with zona pellucidazona pellucida

�� follicular cellsfollicular cells (several layers)(several layers)

�� antrum folliculi antrum folliculi withwithliquor folliculiliquor folliculi

��maturemature ((GraafianGraafian) ) folliclefollicle– 10-25 mm� large (125 µm) primary oocyteprimary oocyte

� cumulus oophorus (ovaricus)cumulus oophorus (ovaricus)�� membrana (stratum) granulosamembrana (stratum) granulosa�� theca folliculi interna et externatheca folliculi interna et externa

�� folliculogenesisfolliculogenesis

�� maturationmaturation ofof thethe ovarianovarian folliclefollicle�� regulated by FSHregulated by FSH

Ovarian follicles

Regnier de Regnier de GraafGraaf

(1641(1641--1673)1673)


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�� regulation of the ovarian cycleregulation of the ovarian cycle::

�� hypothalamushypothalamus

�� gonadotropingonadotropin--releasing hormone releasing hormone

(GnRH)(GnRH)

� portal system

�� adenohypophysisadenohypophysis –

gonadotrope hormones:

�� folliclefollicle--stimulating hormone stimulating hormone (FSH)(FSH) –

folliculogenesis � estrogensestrogens

�� luteinizing hormone luteinizing hormone (LH)(LH) –

ovulation and development

of corpus luteum � gestagensgestagens

Hormonal control of ovarian functionsHormonal control of ovarian functions


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� in humans and in most mammals:� one ovarian follicle occasionally

contains two or three clearly

distinguishable primary oocytes

� usually degenerate before reaching maturity

� twins or triplets

� one primary oocyte contains two or three nuclei� die before reaching maturity

� abnormal spermatozoa – up to 10% of all spermatozoa

� abnormal head or tail

� giants or dwarfs

� sometimes are joined

� lack normal motility and probably do not fertilize oocytes

Abnormal gametesAbnormal gametes


20 Thank youThank you……

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