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 http://courses.jax.org 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 http://phenome.jax.org/pub‐cgi/phenome/mpdcgi?rtn=strains/details&stocknum=000651 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 jaxservices@jax.org • 1-800-422-6423 • 1-207-288-5845 • www.jax.org/jaxmice [...]... Cook MJ.  1965.  The Anatomy of the Laboratory Mouse http://www.informatics.jax.org/cookbook/ 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 – 35 days • Transport to epididymis for storage and maturation (motility) • For IVF, collect sperm from the epididymis... Female Anatomy Cook MJ.  1965.  The Anatomy of the Laboratory Mouse http://www.informatics.jax.org/cookbook/ Oocyte (Egg) Production Oocyte (Egg) Production • Females born with finite number of oocytes 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...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  • • • • • Reproductive Characteristics... Leave mating pairs together L ti i t th www.jaxmice.jax.org/support/husbandry/index Troubleshooting Non Reproductive Mice Troubleshooting Non Reproductive Mice • My mice… y ce… – Don’t get pregnant – Get pregnant, but never give birth – Give birth, but pups die – Not enough pups Troubleshooting • • • • • Has anything in the room changed? Has anything in the room changed? Do the animals appear healthy?... Oxford University Press.     www.informatics.jax.org/silver/ Reproductive Success:  Environment Effects Reproductive Success: Environment Effects • Nutrition • Light cycle and intensity (14hr light/10hr dark) Stress… noise, vibrations, odors, over handling • Stress noise vibrations odors over‐handling – Breeding cessation – Resorption of fetuses of fetuses – Cannibalism of litters • Health status Health status • Seasonal effects... Estrus & Ovulation under Neuroendocrine Control Neuroendocrine Control Hypothalamus (GnRH) Pituitary (E & P) (Inhibin) (FSH & LH) – e.g. seasonal non‐cycling Ovary (E & P) (Pg) • Reproductively senescent p y Uterus The Estrous Cycle The Estrous Cycle Stages ( 4 days per cycle) Stages (~4 days per cycle) • • • • Proestrus (13 hrs) Estrus‐ ovulation (15 hrs) ( ) Metestrus (13 hrs) Diestrus (56 hrs) Cycle Interruption... inbred mice Month of the year Mating Options Mating Options • Pair:  one female x one male • Trio:  two females x one male (same cage) – “Aunting” phenomenon • Harem:  single male, more than two females  – NOT recommended NOT recommended • Male rotation:  two females x male (week 1),  same male, two new females (week 2) same male two new females (week 2) – Single mutant male, need many offspring – Male has a very short lifespan (neuro. mutants)... Induces ovulation ~12 hrs post hCG • Considerations: – Mating occurs in proestrus/early estrus ~mid‐night (dark cycle) – Superovulation success is strain specific – Size/age Reproductive Characteristics of Inbreds Strain Productive  matings Weeks at  first mating Litter  No. of Relative  size litters fecundity Response to  superovulation 129/SvJ 75% 7.9 5.9 4.1 18.1 High A/J 65% 7.6 6.3 2.9 11.9 Low  AKR/J 84% 6.6 6.1 2.2... Are nearby strains having problems? Are nearby strains having problems? What is the breeding history? Is this strain prone to problems? Is this strain prone to problems? Strategies Non Productive Males Strategies—Non‐Productive Males • • • • Mate to new female Mate to new female Check for copulation plug Surgically evaluate reproductive tract Surgically evaluate reproductive tract Interventions: – Artificial Insemination... induce estrus Pheromones in male urine induce estrus  in females • used to synchronize estrus in females Photo:  Memorial University of Newfoundland president’s report Estrous Cycle Interruption: Pheromones Estrous Cycle Interruption: Pheromones Bruce Effect ‐ 1959 • Exposure of a pregnant female to  an unknown male results in pre‐ or  post implantation failure post‐implantation failure Hilda Margaret Bruce . Reproductive Biology of the Reproductive  Biology  of  the  LaboratoryMouse Jim Yeadon, PhD Jim  Yeadon,  PhD TechnicalInformationScientist Over. 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