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CONTINUING EDUCATION IN TOXICOLOGIC PATHOLOGY REPRODUCTIVE SYSTEM (PDF)

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					   CONTINUING EDUCATION IN TOXICOLOGIC PATHOLOGY
            REPRODUCTIVE SYSTEM

ORGANIZED BY SOCIETY FOR TOXICOLOGIC PATHOLOGY IN INDIA (STPI)

                        OCTOBER 29-31, 2010

         The Atria Hotel, # 1, Palace Road, Bangalore - 560 001
             INTRODUCTION TO JAI RESEARCH
                                    FOUNDATION




JAI RESEARCH FOUNDATION A Global Contract Research Organisation   1
 JAI RESEACH FOUNDATION




                                       JRF India
   JRF America                                                    JRFI UK




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                         JRF has endorsement of compliance with the OECD
                           Principles of Good Laboratory Practices by the
                         Ministry of Health, Welfare and Sport, Government of
                         The Netherlands as well as GLP monitoring Authority
                        of the Government of India. JRF is also recognized by
                           Nuclear Regulatory Commission, Government of
                         India; as well as Association for Assessment and
                        Accreditation of Laboratory Animal Care International
                                             "AAALAC".


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         SPONTANEOUS LESIONS IN FEMALE
                    REPRODUCTIVE SYSTEM
        IN SHORT AND LONG TERM STUDIES

                          DR. M. C. PRASAD
                     JAI RESEARCH FOUNDATION
                           VAPI – 396 195
                              GUJARAT



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 RODENTS IN TOXICITY STUDY
   • Rats and Mice most commonly used rodents
   • Rats used in about 70-80 % studies
   • Mice used in 80-90% studies
   • Short term: conducted to establish dose for
     chronic / carcinogenicity studies, duration upto
     90 days
   • Conducted to study haematological /
     biochemical / pathological alterations of test
     substance at different intervals/termination
     beyond 90 days.

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 SPONTANEOUS LESIONS

     Development/occurrence of lesions at its own in an
     animal species


     Occurrence rate depends upon species, age,
     strain, husbandry practices and agro-climatic
     condition



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REPRODUCTIVE SYSTEM

• Importance of System: Continuity of species in nature, only
                System
  gender based system in medical/Vety. Sci, further stresses its
  importance

• Male System: Contribution limited upto fertilization of ovum
       System
• Female System: Implantation of ferti. ovum, intrauterine
         System
  develop, parturition, neonatal care including feeding upto wearing
  stage in rats

• Reproductive organs : Ovaries, uterus/cervix vagina,
  mammary glands, etc.



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 SPONTANEOUS LESIONS
• Congenital : Agenesis, disgenesis, hamartoma, ectopic tissues
• Degenerative : Degeneration, necrosis, cyst, atrophy,
  pigmentation, mineralization / concretion
• Inflammatory and Vascular Changes : Inflammatory
  changes in different organs, congestion, angiectasis
• Hyperplastic Lesions: Hyperplastic changes in different organs
               Lesions
• Neopalstic lesions: Various Neopalstic lesions
             lesions
• Miscellaneous Lesions : Uncovered under above heads




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COMMON LESIONS IN RATS AND MICE
                           SHORT TERM
                            OVARIES
        RATS                                            MICE

       Agenesis (uni/bilateral)                       Teratoma
       Dysgenesis                                     Cysts
       Ovotestis                                      Oophritis
       Cysts                                          Klebsellosis
       Mycoplasmosis                                  Follicular necrosis
       Abscessation                                   (granulosa cell necrosis)
       Congestion                                     Angiectasis
       Angiectasis

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COMMON LESIONS IN RATS AND MICE


   RATS                                                           MICE
                                  LONG TERM
       Fatty metaplasia, atrophy                      Granulosa cell hyperplasia
       pigmentation – haemo, ceroid
                                                      Tubulostromal hyper./
       Interstitial cell hyperplasia                  adenoma/ adenomacarcinoma
       Granulosa cell hyper./tumour
                                                      Cystadenoma/carcinoma
       Epithelial cell hyperplasia
                                                      Granulosa cell tumour – rare
       Luteoma
                                                      Luteoma
       Tubulostromal adenoma /
       carcinoma                                      Haemangioma
       Sertoli form tumour                            Pigmentation : haemo/cerasoid
       Mesothelioma - rare                            Mesothelioma


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UTERUS


   RATS                                                           MICE
                              SHORT TERM
       Agenesis –                                     Agenesis
       complete/partial                               Luminal dilation
       harmartoma                                     Metritis – infection
       Luminal dilation                               Polyarteritis/Thombus
       Metritis – infection                           Angiectasis
       Polyarteritis/Thrombus                         Deciduoma
       Deciduoma                                      Endomat. polyp.
       Endometrial polyp

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UTERUS

                                LONG TERM
   RATS                                                           MICE

       Atropy                                         Atrophy
       Cystic endomat. hyper                          Cystic endomet. hyper.
                                                      Endomat. adenoma/adeno-
       Endonet. adenoma/                              carcinoma
       adenocarcinoma                                 Leiomyoma / - sarcoma
       Leiomyoma /                                    Endomat. stromal sarcoma
       leimyosarcoma                                  Adenomyosis
                                                      Squamous cell metaplasia




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CERVIX/VAGINA

                             SHORT TERM
   RATS                                                           MICE

       Imperfect vagina                               Atrophy
       Vaginal dilation                               Angiectasis – extension
       Atrophy                                        from uterus
       Sq. epithelial cyst in cervix                  Sq. epithelial cyst in
       and vagina                                     cervix and vagina
       Vaginitis/cervicitis - rare




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CERVIX/VAGINA

                             LONG TERM
   RATS                                                           MICE

       Sq. epith cell hyper./                         Sq. epith cell hyper/carcinoma
       papillioma/carcinoma                           Vaginal polyp
       Vaginal polyp                                  Granular cell tumour
       Granular cell tumour                           Vaginitis/cervicitis
       Leiomyoma/-sarcoma                             Angiectasis – extension from
       Fibrosis                                       uterus
       Adenocarcinoma of endocervix
       Adenoacanthoma




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MAMMARY GLANDS

                             SHORT TERM
   RATS                                                           MICE

       Ductal/alveolar degen.,                        Ductal/alveolar degen.
       pigmentation                                   pigmentation




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MAMMARY GLANDS

                             LONG TERM
   RATS                                                           MICE

       Cystic changes: cystic degen.                  Cystic changes : cystic degen.,
       galactocele, ductectasis,                      galactocele, ductectasis,
       periductal fibrosis                            periductal fibrosis
       Fat necrosis                                   Fat necrosis
       Lobular hyper/focal hyper                      Lobular hyper/focal hyper
       Fibroadenoma                                   Adenocarcinoma
       Lipoadenoma/adenolypoma                        Sq. carcinoma – ductal origin
       Myoepithelioma – rare, origin                  Myoepithelioma – rare, origin –
       ductal myoepith                                ductal myoepith




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                 Ovary: Atrophy having marked stroma




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                 Ovary: Stromal fatty metaplasia (arrow)




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                           Ovary: Angiectasis



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                   Ovary: Follicular cysts (C)




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                              Ovary: Luteal cyst (c)




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                          Ovary: Epidermoid cyst (K- keratin)




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                           Ovary: Tubular hyperplasia




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                        Ovary : Interstitial cell hyperplasia




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                        Ovary:Granulosa cell tumour




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                        Ovary:Sertoli form tumour




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                                 C              C


                                  C
                     Uterus: Endometrial cystic hyperplasia (C)




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                                            P



                          Uterus: Endometrial polyp (P)




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                 D




Uterus : Deciduoma (D)

                                            Uterus : Deciduoma-large
                                                     epithelial cells

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                       Uterus: Adenocarcinoma




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                       Uterus: Adenomyosis




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                         Cervix: Squamous epithelial cyst




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                       Vagina: Papilloma arising in fornix




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                                           C

                          Vagina/Cervix: Hyperplasia, C- Cervix




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                         Vagina: Squamous cell carcinoma




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                          Cervix: Granular cell tumour




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                          Mammary Gland: Alveolar degeneration




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                      Mammary Gland: Ductectasis




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                        Mammary Gland: Focal hyperplasia (arrow)




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                       Mammary Gland: Lobular hyperplasia




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                         Mammary Gland:Adenofibroma




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                          Mammary Gland:Adenolipoma




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                        Mammary gland:Adenocarcinoma




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                        Mammary gland:Adenocarcinoma (comedo pattern)




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