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.

Harlan Laboratories 8

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%

Harlan Laboratories 10

Squamous papilloma: approx. 4%Squamous carcinoma: approx. 4%

Problems: Vagina - Hamster

Harlan Laboratories 11

Background Lesion in Uterus

Implantation site

• Foamy macrophages • Fibrosis• Hemosiderin

Harlan Laboratories 12

Background Lesion in Uterus

Squamous cyst

Cystic hyperplasia Endometrial fibrosis

Harlan Laboratories 13

Induced Lesion in Uterus

Normal estrus Atrophy: Oxoplatin

Atrophy: Ca-channelblocker Atrophy: Corticosteroid

Harlan Laboratories 14

Induced Lesion in Uterus: Phytoestrogens

Endometrial hyperplasia

Hydrometra Endometrial inflammation

Harlan Laboratories 15

Induced Lesions in Cervix: Phytoestrogens

Increased apoptosis, squamous metaplasia

Harlan Laboratories 16

Induced Lesions in Cervix: Phytoestrogens

Basal and epithelial cell hyperplasia

Harlan Laboratories 17

Induced Lesions in Vagina

Mucoid plaque: Ca-Channel blocker

Massive Hemorrhage: Doxorubicin

Harlan Laboratories 18

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)

Harlan Laboratories 20

Induced Lesions in Vagina

Basal cell and epithelialhyperplasia(phytoestrogen)

Massive mucification (5 α-Reductase Inhibitor)

Harlan Laboratories 21

Background Lesions: Ovaries

Dilated bursa

Senile atrophy

Harlan Laboratories 22

Background Lesions: Ovaries

Mesothelial hyperplasia

Harlan Laboratories 23

Age-Related Lesions: Ovaries

Fibrosis

Interstitial cellhyperplasia

Harlan Laboratories 24

Age-Related Lesions: Ovaries

Sertoli’s cell hyperplasia

Harlan Laboratories 25

Induced Cycle Interruption: Ovaries – Ca-Channel Blocker

Oocyte atresiaand hyperplasia ofInterstitial cells

General inanition at high dose

Harlan Laboratories 26

Induced Hemorrhage: Ovaries - Doxorubicin

Massive bursal hemorr-hage of unknown me-chanism at high dose

Harlan Laboratories 27

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)