ON TESTIS AND EPlDlDYMlS OF RATS - Pondicherry University ...

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clrects. reproductive and developmental toxicity, tumour production i~ctivity. neurotoxicity, chloracne and other dermal effects and the disruption of several endocrine-response pathways (Safe, 2001). TCDD has been shown to inhibit estradiol induced responses (Safe, 1995). uterine wet weight increase, peroxidase activity, progesterone receptor binding, epidermal growth factor receptor binding (Safe c.1 01.. 1998). TCDD has also been reported to induce drug-metabolizing enzymes, modulate expression of many other genest gene products (Safe, 2001). TCDD has been shown to increase the respiratory tract cancer in female but not in male rats (Kociba er al.. 1976). 1.3.1.1 Effect of TCDD on various organs TCDD has been reported to alter a variety of organ systems in different species. Loss of body weight is a characteristic sign observed in most animals given a sub-lethal dose of TCDD. The weight loss usually manifests itself within a few days after exposure and results in a substantial reduction of the adipose (Peterson el ol., 1984) and muscle tissues (Max and Silbergeld, 1987). With sub-lethal doses of TCDD, a dose-dependent decrease in body weight gain occurs (Kociba el ul.. 1976). The greatest species-specific differences in toxicity concern pathological alterations in the liver of the TCDD treated rats. Lethal doses to guinea pigs do not result in liver damage, which is comparable to the liver lesions described in rabbits and rats or to liver changes observed in mice (McCOM~~I el a/.. 1978; Moore rr ul.. 1989; Turner and Collins, 1983). Thymic atrophy has been found in all animal species given lethal doses of TCDD. Treatment of animals with TCDD inhihits the bone marrow hemopoiesis in mice, both in vrvo and in virro, by directly altering the colony growth efficiency of stem cells (Chastain and Pazdernik. 1985; I.ustcr cr 111.. I V85). Among other signs and symptoms hepitic porphyrio. licmorrliagcs in vurious organs. lesticular atrophy, reduced prostate weight, reduced uterine weight. increased thyroid weight. lesions of the adreliul glands. inhibited bonc marrow hc~ni~topoi~sis. decreased serum albumin and increased serum triglycerides and free €any acids.
Effect of TCDD on heart muscle has also been reported in guinea pigs and rats (Brewster et al., 1987; Canga et al., 1988). 1.3.1.2 Effect of TCDD on male reproduction TCDD decreases testis and accessory sex organ weights, causes abnormal testicular morphology, decreases spennatogenesis and reduces fertility when given to adult animals in doses sufficient to reduce feed intake andl or body weight. Some of the effects have been reported in chicken, rhesus monkeys, rats, guinea pigs, and mice treated with overtly toxic doses of TCDD (Allen and Lalich, 1962; Khera and Ruddick, 1973; Kociba er al., 1976; Chahoud er al., 1989; Moore et al., 1989). Impaired division and/ or increased attrition of germ cells during the conversion of leptotene spermatocytes to spermatowa and/ or by a concomitant reduction in Sertoli cell number have been reported in the rats treated with TCDD (Mably et al., 1992). Effects of TCDD on spermatogenesis are characterized by loss of germ cells, the appearance of degenerating spermatocytes and immature spermatozoa within the lumen of the seminiferous tubules and a reduction in the number of tubules containing mature spermatozoa in various species (Allen and Lalich, 1962; Chahoud rr a/., 1989). Prenatal exposure to TCDD has been shown to interfere with fetal development at doses lower than those causing overt toxicity in adult animals. Exposure to TCDD during development produces alterations in the reproductive systems of the developing pups, delayed puberty and reduced sperm counts in males and malformations in the external genitalia of females (Hurst rr al.. 2000). In urero and lactational exposure of male rats to TCDD profoundly altered ontoyeny of the reproductive system and caused reduction in the anogenital distance, delayed testis descent and reduction in the weights of the testis, epididymis and accessory sex organs throughout sexual development. The number of sperm in the epididymis gets reduced in the TCDD treated rats (Faqi er al., 1997). Effects of TCDD on the male reproductive system are believed to be due to an androgenic deficiency (Gray el ul.,
Page 1 and 2: FUNCTIONAL STUDIES ON THE EFFECTS O
Page 3 and 4: ACKNOWLEDGEMENTS I wish to express
Page 5 and 6: TABLE OF CONTENTS Page No ACKNOWLED
Page 7 and 8: TABLE OF CONTENTS (Continued) Deter
Page 9 and 10: TABLE OF CONTENTS (Continued) Effec
Page 11 and 12: TAULIC OF CON'I'ISN'I'S (C'untinued
Page 13 and 14: xi LIST OF TABLES (Continued) I'agc
Page 15 and 16: Table 24a Table 24b Table 24c Table
Page 17 and 18: Fig. 1 Fig. 2 Effect of TCDD on the
Page 19 and 20: Fig. 12c Fig. 12d Fig. 13 Fig. 14a
Page 21 and 22: LIST OF FIGURES (Continued) Fig. 23
Page 23 and 24: LH M PL mg mRNA N AD NADH NADP NADP
Page 25 and 26: layers, an outer layer of visceral
Page 27 and 28: tubular epithelium and continually
Page 29 and 30: lmn~unization of monkeys against FS
Page 31 and 32: and this reaction is catalyzed by t
Page 33 and 34: extratubular environment or synthes
Page 35 and 36: the most active in protein secretio
Page 37 and 38: 1958). A rapid fall in serum testos
Page 39: have also been reported in the rats
Page 43 and 44: 1.4 Effect of oxidative stress on m
Page 45 and 46: 2 SCOPE OF THE PRESENT STUDY There
Page 47 and 48: 3 MATERIALS AND METHODS 3.1 Animals
Page 49 and 50: Subgroup III: Administration of TCD
Page 51 and 52: choppcd with the help of sharp razo
Page 53 and 54: anti-FSH antibody. After incubation
Page 55 and 56: lust sped (500 to 700 rpm) on an or
Page 57 and 58: 3.13.4 Quantitative determinntiun u
Page 59 and 60: The plates were dried by inverting
Page 61 and 62: centrifuged at 3,500 g for I5 min o
Page 63 and 64: 3.17 Preparation of tiasue humogena
Page 65 and 66: supcrnutant was taken. Hlunk was pr
Page 67 and 68: 3.21.4 Assay of glutathione peroxid
Page 69: 4 RESULTS 4.1 Administration of TCD
Page 72 and 73: seminiferous tubules was found to b
Page 74 and 75: fractions of rat testis as compared
Page 76 and 77: 4.1.11.1 Effect of TCDD on the prod
Page 78 and 79: 4.2 Co-administration of TCDD and v
Page 80 and 81: 4.2.8 Effect of co-administration o
Page 82 and 83: 4.2.11.5 Effect of co-administratio
Page 84 and 85: Table I b. Effect of TCDD on the we
Page 86 and 87: Table 4. Effect of TCDD on the seru
Page 88 and 89: Table 7b. Effect of TCDD on the pro
Page 90 and 91:
Table 8c. Effect of TCDD on the lev
Page 92 and 93:
Table 9d. Effect of TCDD on the act
Page 94 and 95:
Table 13. Effect of TCDD on the ant
Page 96 and 97:
Table 15. Effect of TCDD on the lev
Page 98 and 99:
Table 16c. Effcct of TCDD on the an
Page 100 and 101:
Table 18a. Effect of co-administrat
Page 103 and 104:
Table 21. Effect of co-administrati
Page 105 and 106:
Table 24b. Effect of co-administrat
Page 107 and 108:
Table 25c. Effect of co-administrat
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Table 26d. Effect of co-administrat
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Table 30. Effect of co-administrati
Page 113 and 114:
Table 32. Effect of caadrninistrati
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Table 33c. Effcct of co-administrut
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5 DISCUSSION 5.1 Significance of th
Page 119 and 120:
Measurement of weights of the acces
Page 121 and 122:
compartment of the cells (Chainy el
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the reduction in daily sperm produc
Page 125 and 126:
eported in the TCDD-treated rats (M
Page 127 and 128:
lilnction is to ililcrccpt lipid pc
Page 129 and 130:
in the animals administered with TC
Page 131 and 132:
protective effects on serum testost
Page 133:
suygcstccl that vivamin 1: conld im
Page 136 and 137:
Fig.4~. ENect of TCDD or TCDD and v
Page 138:
tE W d In w it I I (,OCX) 3s PUB (,
Page 142 and 143:
Fig. 7c. Effect of TCDD or TCDD and
Page 145 and 146:
u 3 f ~ = m w * N O .- ~Slew aew en
Page 147 and 148:
Fig.lOb. ENmt of TCDD or TCDD and v
Page 151:
Fig. 1Ir Effect of TCDD or TCDD md
Page 158 and 159:
Fig. 14c. Effect of TCDD or TCDD an
Page 160 and 161:
Fig. 16b. Effect of TCDD or TCDD an
Page 164 and 165:
Fig.18~. EKect of TCDD or TCDD and
Page 166 and 167:
1 1.2 l4 Fig. 19b. ENect of TCDD or
Page 168 and 169:
Fig. ZOb. Elkt of TCDD or TCDD and
Page 171 and 172:
Fig. 21. Effect olTCDD or TCDD and
Page 173 and 174:
Fig. 22c. Effect of TCDD or TCDD an
Page 175 and 176:
Fig. 24b. Eflect ofTCDD or TCDD and
Page 177 and 178:
7 REFERENCES Aitken RJ, Irvine DS,
Page 179 and 180:
Chitm KC, Latchoumycandanc,C, Mathu
Page 181 and 182:
Flsher JS, Turner KJ, Brown D, Shar
Page 183 and 184:
Hornsby PJ. Regulation of cytochrom
Page 185 and 186:
Latcboumycandane C, Chitra KC, Math
Page 187 and 188:
Moore RW, Panona JA, Bookstaff RC,
Page 189 and 190:
Rommerts FFG, Cooke BA, Van Der Kem
Page 191 and 192:
Slaunwhite WR, Burgett MJ. h virro
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1.1 Preparation of dosing solution
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1.4.6 Wash concentrate One bottle,
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1.7.3 Estradiol controls Two vials.
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1.1 1.2 Orcinol(6%) 6 g of orcinol
Page 201 and 202:
1.16.2 Horseradish peroxidase (8 Un
Page 203 and 204:
1.20 Superoxide dismutase 1.20.1 Tr
Page 205 and 206:
1.24.2 Thiobarbituric acid (TBA; 0.
Page 207 and 208:
Chronic effect: of enclosulfan on t
Page 209:
enbw1h1.W mu IUY Wcab unpiliml~t at
Page 212 and 213:
cbniuis 11~11 b"nci:~lc ~wlive oxyg
Page 214 and 215:
DNA, RNA ;uxl Wcin wcrr abarval, wh
Page 216 and 217:
Mt~~m(10-lZsu&)vacob- Wfmn Ihehml ~
Page 218 and 219:
New Delhi, llrliil Ib SCI~KK Rcm& M
Page 220 and 221:
tiii~lc rcprmluction or rut (Cllitr
Page 222 and 223:
wciglit (b.wt.) per day for 45 days
Page 224 and 225:
0.1 00 01 " 0.8 I . .lo Dl* rcnn IW
Page 226 and 227:
Chilr:~. K.C.. L!olnn!myci!~dum. C.
Page 228 and 229:
C. hteboumyeradlos . KC. CMtn . P.P
Page 230 and 231:
I. 1 Ilal 01 2 1.7 # I c I ~ ~ L I
Page 232 and 233:
Fin. L Corrclatwn bclwfcn "perm cou
Page 235:
Iionshii nepmdvctivc mxicity ad upt
Page 240 and 241:
o. Glutathione reductage mg pmWn mg
Page 242 and 243:
IOWAME -. Tor. #558517 PME: 9 SESS:
Page 244 and 245:
JOBNAME: Rqm. Tm. M5W7 PAOB: 11 SBS
Page 246 and 247:
t 02 ELSEVIER Toricology OM) (2W1)
Page 248 and 249:
---- - wcre obtu~ncd from E-Monk. G
Page 250:
3.2. A,III~AILNI syrlo~t of ,nIroch
Page 253 and 254:
Uc,#!dy. SC. N;tdcru. S , 1% Conlrb
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