Reproductive Biology of the Laboratory Mouse docx

Reproductive Biology of the
Reproductive

Biology

of

the

LaboratoryMouse
Jim Yeadon, PhD
Jim

Yeadon,

PhD
TechnicalInformationScientist
Over 80 Years of Research Expertise
Over

80

Years

of

Research

Expertise
Leveragingthepowerofgeneticsinthe
search for cures to human

disease
search

for

cures

to

human

disease
Nonprofitresearchinstitutefoundedin
1929inBarHarbor,Maine
TheJacksonLaborator
y
y
Rh
iii i
R
esearc
h
:
i
nvest
i
gat
i
nggenet
i

cs
andbiologyofhumandisease
Resources: JAX
®
Mice&Ser vices,
bioinformaticsdata,technical
publicationsandmore…
Education: world‐classcourses,
internshipsandotherprograms

JAX
®
Mice
TheGoldStandardforBiomedicalResearch
• NIHfundedresource
• 4,500str ainsandgrowing
ll hd ll
–
2.7mi
ll
ionmices
h
ippe
d
annua
ll
y
– 16,000investigatorsglobally
• Unsurpassedgeneticquality&animalhealth
• Bestcharacterized&referenced~100newpubs/week

• Commoninbredstrains(C57BL/6J,BALB/cJ,DBA/2J)support
development/collection of specialty strains and other valuable
development/collection

of

specialty

strains

and

other

valuable

communityresearchresources
Online Resources
Online

Resources
®
b
• JAX
®
MiceData
b
ase
www.jax.org/jaxmice
f

• MouseGenomeIn
f
ormatics
www.informatics.jax.org
h b
• MouseP
h
enomeData
b
ase
www.jax.org/phenome
d i
•
A
n
d
manymoreun
i
queresources
/>BALB/cJ–BestCharacterized
BALB/cJ–BodyComposition–Fat
TheJacksonLaboratory
GeneticStabilityProgram
USpatent7,592,501
JAX
®
Services
JAX
Services
• Breeding&colon ymanagement

• Revolutionarycryopreservation&recovery
• Phenotyping&efficacytesting
• Geneticresearchservices
• Surgical&preconditioningservices
U f itith li d tt
f
th
t it
•
U
seo
f

i
nnova
ti
ve
t
ec
h
no
l
og
i
esan
d
s
t
a
t

e‐o
f
‐
th
e‐ar
t
equ
i
pmen
t
• Flexibilitytodevelopcustomizedapproaches
JAX®Mice&Serv ices
• 1-800-422-6423 • 1-207-288-5845 • www.jax.org/jaxmice
Overview
ReproductiveBiologyoftheMouse
• Reproductivecharacteristics
•
Determining gender
Determining

gender
• Maleandfemaleanatomyandgameteproduction
•
Reproductive states in female mice
Reproductive

states

in


female

mice
• Estrouscycle
–
Stage detection
–
Stage

detection
– Interruption
•
Troubleshooting non
productive animals
•
Troubleshooting

non
‐
productive

animals

Re
p
roductiveCharacterist ics
p
• Sexualmaturity:5to8weeks
• Estrusc
y

cle:~4da
y
s
;
s
p
ontaneous
y y; p
• No.eggsovulated:6‐16(variablebystrain)
•
Gestation: 18 5
21 days
•
Gestation:

18
.
5

–
21

days
• Littersize:2to12+pups
• Productivebreedinglife:~7‐8months
SilverLM.(1995). MouseGenetics:ConceptsandApplications
OxfordUniversityPress.www.informatics.jax.org/silver/
SilverLM. 1995. MouseGenetics:ConceptsandApplications,Oxford
UniversityPress.Availableonlineatwww.informatics.jax.org/silver
Sex Determination: Adult Mice

Sex

Determination:

Adult

Mice
MALE
FEMALE
MALE
FEMALE
Sex Determination: Weanlings
Sex

Determination:

Weanlings
MALE
FEMALE
MALE
FEMALE
Sex Determination: Newborns
Sex

Determination:

Newborns
MALE
FEMALE
MALE

FEMALE
Male Anato my
Seminal Vesicles
Male

Anatomy
Bladder
Vas Deferens
Prostate
Urethra
Coagulating
Gland
Epididymis
Testis
Gland
Bulbourethral Gland
Penis
Testis
Male Anato my
Male

Anatomy
CookMJ.1965.TheAnatomyoftheLaboratoryMouse
/>Sperm Production
Sperm

Production
• Diploidspermatogonialstemcells– lifetimesupply
•
12 stages of spermatogenesis in the

seminiferous
tubules
•
12

stages

of

spermatogenesis

in

the

seminiferous
tubules
– 35days
• Transporttoepididymisforstorageandmaturation(motility)
• ForIVF,collectspermfromtheepididymis
/>Female Anatomy
Female

Anatomy
Bursa Ovary
Oviduct
UterineHorn
UterineLumen
Cervix
Cervix

Vagina
Vulva
(
external
g
enitalia
)
( g)
Female Anatomy
Female

Anatomy
CookMJ.1965.TheAnatomyoftheLaboratoryMouse
/>Oocy te (Eg g) Production
Oocy te

(Egg)

Production
• Femalesbornwithfinitenumberofooc
y
tes
y
• At6weeks,eachovaryhas10,000 oocytes
• 6‐16oocytesovulateover2‐3hoursevery
4‐5daysinmice
Reproductive States of Adult Female Mice
Reproductive

States


of

Adult

Female

Mice
•
Cycling
Neuroendocrine Control
Estrus&Ovulationunder
Cycling
• Pregnant
d
(GnRH)
Neuroendocrine

Control
Hypothalamus
• Pseu
d
opregnant
• Anestrus
(FSH & LH)
Pituitary
Ovary
(E & P)
(Inhibin)
– e.g.seasonalnon‐cycling

• Re
p
roductivel
y
senescent
(E & P)
Ovary
(Pg)
py
Uterus
The Estrous Cycle
The

Estrous

Cycle
Stages (
~
4 days per cycle)
CycleInterruption
Stages

(4

days

per

cycle)
• Proestrus(13hrs)

• Estrus‐ ovulation
(
15hrs
)
• Mating
• Pheromones
( )
• Metestrus(13hrs)
• Diestrus(56hrs)
• Environment
• Exogenoushormones
Selectproestrus/estrusfemales:
–
Timedmatin
g
s
g
– Pseudopregnantfemales
• vasectomizedmalesrequired
GrassoPetal.1998.BiolReprod 58(3):821‐5.PMID:9510972
DetectingEstrousCycleStage
(Polymorphonuclearleukocytes)
(cornifiedepithelialcells)
Estrus Metestrus DiestrusProestrus
Champlin,Dorr,Gates.1973.BiolReprod 8(4):491‐4.PMID:4736343
Estrous Cycle Interruption: Mating
Estrous

Cycle


Inte rruption:

Mating
Femaleinproestrus Vaginalplugaftermating
• Bestobservedearlymorning
• Producedbyseminalvesicleandcoagulatinggland
• Preventsmatingwithothermales
• Plugdoesnotguaranteepregnancy
•
Mating stimulation (not plug) induces pseudopregnancy
Mating

stimulation

(not

plug)

induces

pseudopregnancy
