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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
Harlan Laboratories 1
Placenta
Trophoblasts
Maternal vascular spaces
Trophospongium
Cytotrophoblasts
Syncytiotrophoblasts
Harlan Laboratories 2
Placenta
b) Labyrinth zone with trophoblasts, maternal vas-cular spaces and fetal vessels (fetus site) Strands from the trophospongiosum extend into the labyrinth.Embryonic capillaries lined by the endothelial cell s.
Reicherts membrane at embryonic site
Harlan Laboratories 3
Placenta
Trophoblasts
Labyrinth zone
Trophospongium
Maternal blood spaces
Embryonal vessles
Harlan Laboratories 4
Placenta
Decidua capsularis (reflex-um): decidua of the endo-metrium covering implan-ted ovum
Labyrinth.
Reicherts membrane
Yolk sac membrane(Vitelline membrane)
Harlan Laboratories 5
Placenta: Thomas Henry Huxley, 1864
Harlan Laboratories 6
Deciduale Reaction (Deciduoma)
• Uterine lining (endometrium) during pregnancy that• Forms the maternal part of the placenta• Formed under the influence of progesterone• Characteristic cells
• High progesterone levels may trigger decidual reacti on in rodents
Tawfik OW, Sagrillo C, Johnson DC, Dey SK. Decidualization in the rat: role of leukotrienes and prostaglandins. Prostaglandins Leukot Med. 29: 221-7 (1987)Miller MM, O’Morchoe CC. Decidual reaction induced by prostaglandin F2α in the mature oophorectomized rat. Cell Tiss Res, 225: 189-199 (1982)
Harlan Laboratories 7
Deciduale Reaction (Deciduoma)
Cellular and vascular changes in endometriumat the time of implantationby hormones.
Most prominent at anti-mesometrial site.
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Deciduoma (mesometrial site): Granulated MetrialGland Cells
Harlan Laboratories 9
Problems: Uterus - Hamster
• Adenoma: approx. 6 %• Adenocarcinoma: up to 70%• Stromal Polyp: approx. 6 %• Leiomyoma: approx. 6%• Leiomyosarcoma: approx. 4%
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Squamous papilloma: approx. 4%Squamous carcinoma: approx. 4%
Problems: Vagina - Hamster
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Background Lesion in Uterus
Implantation site
• Foamy macrophages • Fibrosis• Hemosiderin
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Background Lesion in Uterus
Squamous cyst
Cystic hyperplasia Endometrial fibrosis
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Induced Lesion in Uterus
Normal estrus Atrophy: Oxoplatin
Atrophy: Ca-channelblocker Atrophy: Corticosteroid
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Induced Lesion in Uterus: Phytoestrogens
Endometrial hyperplasia
Hydrometra Endometrial inflammation
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Induced Lesions in Cervix: Phytoestrogens
Increased apoptosis, squamous metaplasia
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Induced Lesions in Cervix: Phytoestrogens
Basal and epithelial cell hyperplasia
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Induced Lesions in Vagina
Mucoid plaque: Ca-Channel blocker
Massive Hemorrhage: Doxorubicin
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Induced Lesions in Vagina
Normal metestrus Spontaneous atrophy
Diestrus with mucoiddegeneration(corticosteroid)Normal diestrus
Harlan Laboratories 19
Induced Lesions in Vagina
Atrophy with keratinizat-ion (corticosteroid) Anestrus (corticosteroid)
Atrophy with cysticmucosal degeneration(PDE4-Inhibitor)
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Induced Lesions in Vagina
Basal cell and epithelialhyperplasia(phytoestrogen)
Massive mucification (5 α-Reductase Inhibitor)
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Background Lesions: Ovaries
Dilated bursa
Senile atrophy
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Background Lesions: Ovaries
Mesothelial hyperplasia
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Age-Related Lesions: Ovaries
Fibrosis
Interstitial cellhyperplasia
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Age-Related Lesions: Ovaries
Sertoli’s cell hyperplasia
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Induced Cycle Interruption: Ovaries – Ca-Channel Blocker
Oocyte atresiaand hyperplasia ofInterstitial cells
General inanition at high dose
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Induced Hemorrhage: Ovaries - Doxorubicin
Massive bursal hemorr-hage of unknown me-chanism at high dose
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Induced Cycle Interruption: Ovaries - 5 α-Reductase Inhibitor
Follicular dilation and reduced corpora lutea
Harlan Laboratories 28
Aromatase inhibitors - Letrozole
• In postmenopausal women aromatase inhibitors successfully lower estrogen synthesis to an increa-sed estrogen synthesis as a consequence of increa-sed in FSH and LH
• FSH stimulates the synthesis of aromatase in granu-losa cells
• LH increases ovarian steroid synthesis in theca cells,especially of androstenedione,
• Therefore, most aromatase inhibitors do not show thedesired effect in women with intact ovarian function
• Aromatase catalyzes the conversion of androgens toestrogens. Junker U: Classic Examples in Toxicologic Pathology (3rd Edition)
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