Making Sperm Flashcards
describe early embryonic development of testis - gen
early development of seminiferous tubules - 2 principle types of cells = germ cells and sertoli cells (encircled by germ cells, first cells to be specified by sry/sox9)
describe early embryonic development of testis - layers and specific cells
tunica albuginea = hard shell of testis
flcs = fetal leydig cells, outside seminiferous tubules
pmcs= peripheral myoid cells - gives structure to seminiferous tubules (elongated cells)
describe early embryonic development of testis - germ cells and vasculature
germ cells = not super organized, but see the 2 cell types
vasculature = red cells = blood vessels, around outer edge and poke down into seminiferous tubules
name parts of anatomy of male reproductive system
seminiferous tubules
epididymis
vas derens
describe seminiferous tubules
250m/testis
sperm production
150-300 mil/day
very long and narrow compartmentalized, spermatogenesis happens here
describe epididymis
has head, body and tail
sperm maturation and transport
tightly coiled
once sperm mature= complete differentiation and pass to epididymis
describe vas deferens
sperm transport
functionally competent now
when do sperm acquire motility
when pass through epididymis
factors or secretions give them motility
is the sperm in the testis functional - explain
yessss
ones in testis = cannot swim well, but do not need to swim to be functional gamete
can use for icsi - inject into egg
describe development of reproductive tract - gen overview
all embryos begin with precursors of male and female
then specifies
leydig cells produce testosterone = wolffian ducts
testis produce amh = inhibits mullerian ducts
*at this stage and location no testosterone in females
describe germ cells - history too
antoine van leeunwenhoek (1632-1723)
identified germ cells
could see sperm swimming around
describe preformationism - history too
proposed by nicolaas hartsoeker (1656-1725)
idea that embryo was directly formed in sperm
egg produced placenta and embryo came from sperm
egg provides nutrients
preformed babies for generations
describe setoli cells - history too
enrico sertoli (1842-1910)
inside seminiferous tubules
role = harbour and support developing germ cells
describe leydig cells - history too
outside seminiferous tubules
synthesize steroids - testosterone and some estrogen
describe structure of seminiferous tubules - histology components
spermatids near lumen
primary spermatocytes
spermatogonia
sertoli cells= close to periphery, have characteristic shape and staining of nuclei
peritubular myoid = cell, very stretched around outside
leydig cells = exist between seminiferous tubules, outside the seminiferous tubules
how many m of seminiferous tubules/man
250m/man
many seminiferous tubules
to 500m
name cells that are similar between spermatogenesis and oogenesis
sertoli and granulosa
leydig and theca
describe how sertoli and granulosa cells are similar (between spermatogenesis and oogenesis)
derived from same precursor cells in embryonic gonad
in direct contact with and support developing germ cells
expresss fsh receptors
describe how leydig and theca cells are similar (between spermatogenesis and oogenesis)
derived from interstitial (cells that are not any other kind of cell) cells of embryonic gonad
are not in direct contact with germ cells
express lh receptors
produce testosterone
describe differences between spermatogenesis and oogenesis - all germ cells
oog = all germ cells produced before birth
sperma = new germ cells produced throughout reproductive live (>100mil news sperm/day = >1000/second), estimate, up to 300mil
describe differences between spermatogenesis and oogenesis - germ line stem cells
oog = no germ line stem cells after birth
sperma = germ line stem cells throughout reproductive life (that give rise to sperm, create new sperm at high levels for whole reproductive life)
describe differences between spermatogenesis and oogenesis - meiosis
oog = enter meiosis before birth
sperma = germ cells enter meiosis throughout reproductive life (as part of differentiation)
describe differences between spermatogenesis and oogenesis - growth and maturation
oog = requires 3-4 months
sperma = requires ~2.5 (2-3) months
describe differences between spermatogenesis and oogenesis - support
oog = many granulose cells support one germ cell
sperma = one sertoli cell supports many germ cells
describe differences between spermatogenesis and oogenesis - meiosis timings
oog = meiosis 1 before fertilization, meiosis 2 after
sperma = both meiotic divisions precede fertilization
describe/compare products of both oogensis and spermatogenesis
oogenesis = 1st meiosis produces 1 polar body, 2nd meiosis produced another polar body, ends up with one gamete
sperma = 4 half gametes
name the 3 stages of spermatogenesis
mitotic proliferation
meiosis including both meiotic divisions
morphological changes (spermiogenesis)
what are ssc - describe
spermatogenic sperm cell
cell that has ability to divide
typically produces one stem cell and 2nd daughter cell differentiates to another cell
where do the ssc live - describe
reside in niche - location that supports stem cells
located near bm of seminiferous tubule
close to periphery
where is the niche close to - explain
blood vessels outside seminiferous tubules may be releasing growth factors, niche exists close to this blood vessel, or cells that provide growth factors - molecules for stem cells to divide and live and sustain sperm production for many years
bmp4 and neuregulin 1 (source unknown)
spermatogenesis - mouse vs human - amount of time
mouse = 35d
human = 75d
describe whole of spermatogenesis - gen
type A1 spermatogonia
type A2 spermatogonia
type A3 spermatogonia
type A4 spermatogonia
(histologically different, undergo mitotic amplification, not as much in humans tho, increase number of cells by mitotic divisions)
intermediate spermatogonia
type B spermatogonia = enter meiosis, triggered by retinoic acid, tells mitotic cells to undergo meiotic division
after 1st meiotic division = primary spermatocytes
after 2nd meiotic division = secondary spermatocytes
2nd meiotic divisions then called spermatids, haploid = spermiogenesis, generates mature sperm
describe sperm output - from mice to men
rodent = 40mil sperm/gram testis tissue/day
monkey = 41 mil sperm/gram testis tissue/day
human = 4.4 mil sperm/gram testis tissue/day- humans have less amplification divisions
describe luminal progression
as enter meiosis, 1st and 2nd divisions and spermiogenesis = moving in seminiferous tubules
begin in niche as ssc, then after divides to type A spermatogonia = located at periphery of seminiferous tubules, as undergoing process = move from periphery to center of seminiferous tubules
must cross through tight junctions
why is luminal progression useful
allows mature sperm to be located in lumen of seminiferous tubule then transferred out to epididymis and vas deferens
brings sperm to right place
describe tight junctions - spermatogenesis
sertoli cells linked to each other by tjs, sticks cell close together, not much can get inbetween
must pass through tjs = tjs much become disassembled, so things can pass through, transiently disassembled- they must
what is on outside vs inside of tjs
sperm and spermatogonia on OUTSIDE
spermatocytes and spermatids on INSIDE
describe sertoli cells
have fsh receptor,
responsive to testosterone produced by leydig cells
essential for process of sperm development to be completed
what is sperm production in adults proportional to
number of sertoli cells generated during fetal life
if have many sertoli cells = will make lots of sperm
describe leydig cells
has lh receptor
produced testosterone
testosterone <–> dihydrotestosterone via 5alpha reductase
estradiol to <–> testosterone (androstenedione) via 17beta-hsd
testosterone <–> estrone (then estradiol) via aromatase
how much testosterone do leydig cells produce
3-10mg of T per day= lots
95%of total testosterone produced by male (other 5% = adrenals)
supports spermatogenesis but also development of secondary sex characteristics
when are androgens required during spermatogenesis
around second meiotic division (after 1st) and when making spermatids = spermiogenesis
when no androgens or receptors for them = sperm differentiation process blocked, cannot produce functional mature sperm
describe in vitro systems for studying spermatogeneis
not as developed as for study of oocytes
where are ssc located
near periphery of seminiferous tubules
where are sertoli cells located
inside seminiferous tubules
which cell type produces testosterone
leydig
describe spermiogenesis
big morphological reshaping of sperm
extensive cellular remodelling - sheds cytoplasm, remodels and end up with
sperm = tail (produces motion, prinicipal piece and mid piece with mitochondrial sheath) and head = acrosome and dna
describe major elements of mature sperm - acrosome - informally
bag of enzymes
Contains factors sperm will need to penetrate protective coat around around - to bind with egg at fertilization
factors that enable fertilization
in acrosome - bag, so will not be lost or used to early
what does acrosome cover
Anterior half of nucleus
what is acrosome derived from
golgi
what happens to acrosme during fertilization
outer membrane fuses with plasma membrane releasing acrosomal contents
what does acrosome contain
numerous enzymes typical of lysosomes
acrosin = inactive proacrosin converted to active form by acrosome reaction
hyaluronidase = breaks down cumuls cell matrix surrounding egg
describe length of sperm tail
55 mu m long in humans (sperm = 60 mu m)
what does tail have/how its organized
typical structure axonemes - microtubules arranged in 9+2 structure
outer dense fibers
mitochodria
describe nucleus of sperm - gen
most unique part of sperm
Extremely condense dna = <5% of somatic volume - non nucleosomal
shrunken, compacted dense bundle
is nucleus of sperm transcriptionally active
no inactive
describe major elements of mature sperm - nucleus - histones and stuff
histones mainly replaced with protamines = sperm specific basic proteins
histones = rich in lysines (+), helps neg charge dna bind, histones replaced by protamines
rich in arginine and cysteine
protamines = + charge, can bind to dna
protamines do not organize dna into nucleosomes
describe chromatin structure - generally usually - standard
nucleosomal structure
dna wraps around octamers, consists of 2 molecules at each of core histones
h2,h3,h3,h4
histone 1 at some place
linker histones between histone
all of this lost in mature sperm
describe nucleoprotein transitions during spermiogenesis
during mitotic phase and meiosis = meiosis/early differentiation = dna organized in typical fashion = active = histones
then post meiotic phase = replaced by transition proteins then
during spermiogenesis = protamines
are all regions of sperm dna replaced by protamines
nooo
some regions of sperm dna that retain their histones, despite widespread condensation and replacement of histones, selective retention
how much of sperm dna remains associated with histones
~15% in humans
you are what your father eats = describe
if eat healthy = histones retained on certain regions of dna - important significance for gene expression after fertilization
if bad diet = maybe histones retained on incorrect parts of dna, remains associated with wrong dna and influences expression of paternal chromatin after fertilization
also could apply to environment/pollution
mans sperm structure could change in non genetic way = affect embryo gene expression (phenotypic development)
describe transgenerational epigenetic inheritance
origin of you are what your father eats
p gen = mouse with specific mutation in kit gene - white spotted phenotype
f1 gen = some carry mutation, some carry 2 wild type genes = idea that maybe no mutation but sperm modified so get white phenotype
what is msci/msuc
meiotic sex chromosome inactivation = msci
meiotic silencing of unpaired chromatin = msuc
describe meiosis - pairing at pachytene - msci
mediated by proteins known as synaptonemal complex
proteins - pairing happens in sperm and egg
describe what happens when x and y chroms paired together - msci - specifically
since unpaired chromatin = same would happen if autosomal chroms do not pair
essential genes on unpaired x (not so much y)
catastrophic of silenced for sperm production = bc many cells need these genes for life
describe meiosis in males - msci
somatic chromosomes = pair normally
2 x chromosomes = pair normally
x and y chromosomes = do not synapse over most of their length, not 2 homologs, only pair at end= pseudoautosomal region - with enough similarities, but no pairing on rest of x = transcriptional silencing on unpaired portion
describe consequences of msci - what actually happens
happens during spermatogenesis bc of dependence on synapsing = so sperm rescue themselves
autosomal genes encoding homologues of x encoded genes become transcriptionally active in meiotic sperm cells = activates and helps compensate
normally silenced by in meiotic sperm cells = becomes active to compensate for silencing of genes on x chrom
x becomes silence and genes on autosome turn on - gene product transcribed off similar gene
what does failure of msci cause
cell death
if gene not silenced = over production of gene bc still will turn on the autosomal genes to compensate, can occur during pachytene = death
describe xyy - msci
xyy –> synapsis of y chrom (bc in early meiosis = abnormal expression of y encoded genes)–> expression of y encoded genes (but should be silenced) –> sterility (only in sperm cells, genes should not be on)
