https://doi.org/10.52973/rcfcv-e34436
Received: 04/04/2024 Accepted: 17/07/2024 Published: 07/11/2024
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Revista Científica, FCV-LUZ / Vol. XXXIV, rcfcv-e34436
ABSTRACT












-1



-1

-1

-1

PP
P
P


P


P
PP
PPP

(P




Key words: 

RESUMEN












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
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
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PP
PP




(P


PP
P
(PP
P
(P




Palabras clave: 

L–Thyroxine induced hyperthyroidism effect on Testicular endoplasmic
reticulum stress and Perk–mediated Nrf2/HO–1 signaling axis of rats
Efecto del hipertiroidismo inducido por L–tiroxina sobre el estrés del retículo endoplásmico
testicular y el eje de señalización Nrf2/HO–1 mediado por benecios de ratas
Gözde Arkalı
1
*, Şeyma Özer Kaya
2
, Songül Çeribaşı
3
, Edanur Güler Ekmen
1
, Mesut Aksakal
1
, Mehmet Çay
1
1
Firat University, Faculty of Veterinary Medicine, Department of Physiology. Elazığ, Türkiye.
2
Firat University, Faculty of Veterinary Medicine, Department of Reproduction and Articial Insemination. Elazığ, Türkiye.
3
Firat University, Faculty of Veterinary Medicine, Department of Pathology. Elazığ, Türkiye.
*Corresponding Author: garkali@rat.edu.tr / g.arkali38@gmail.com
L-Thyroxine induced Hyperthyroidism / Arkali et al. _________________________________________________________________________________

INTRODUCTION


1











6




8


9




11
























MATERIAL AND METHODS
Animals and experimental design




Rattus norvegicus



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



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6
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

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


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

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









18
Enzyme linked immunosorbent assay and oxidative stress analysis








 





19
et al


-1





TABLE I
The table of Johnsen Score
Score Histologic Findings Score Histologic Findings
10
Spermatogenesis is complete, germline epithelium is of regular
height, and TSC lumens are of normal diameter.
9
Numerous spermatozoa in TSC, disorganization of germinal
epithelium and sequestration of germinal cells, TSC lumen occluded
8 Less than 5–10 spermatozoa are present in each TSC lumen
7
No spermatozoa in TSC lumen, numerous spermatids, spermatocyte
and spermatogonia present
6
No spermatozoa in TSC lumen, 5–20 spermatids, numerous
spermatocytes and spermatogonia present
5
No spermatozoa and spermatids in the TSC lumen, numerous
spermatocytes and spermatogonia present
4
There are no spermatozoa and spermatids in the TSC lumen, less
than 5 spermatocytes, but numerous spermatogonia in each TSC.
3 TSCs have only spermatogonia.
2 Germinal cells completely absent, only Sertoli cells are present
1 All TSCs are cell–free.
_____________________________________________________________________________Revista Cientifica, FCV-LUZ / Vol. XXXIV, rcfcv-e34436


-1
] 


-1

Western blot analysis

















 (








Spermatological parameters analysis




















Histopatological analysis and determination of Johsen Skoru





18



Statistical analysis



t

P
RESULTS AND DISCUSSION


(PPP
6










P
P

6


Control Hyperthyroid
0.0
0.5
1.0
1.5
fT3 (ng·mL
-1
)
✱✱
Control Hyperthyroid
0
100
200
300
400
500
Final Body Weight (g)
✱✱✱
1 2 3 4 5 6 7 8
25
30
35
40
45
50
Weeks
Food Intake (g·rat
-1
·day
-1
)
Control
Hyperthyroid
***
***
***
1 2 3 4 5 6 7 8
0
50
100
150
Weeks
Water Intake (g·rat
-1
·day
-1
)
Control
Hyperthyroid
***
***
***
Control Hyperthyroid
0
5
10
15
20
25
fT4 (pmol·L
-1
)
✱
Control Hyperthyroid
0.0
0.2
0.4
0.6
0.8
TSH (mIU·L
-1
)
✱✱
FIGURE 1. (A) Serum fT3 levels of groups (P<0.01). (B) Serum fT4 levels of groups (P<0.05). (C) Serum TSH levels of groups (P<0.01). Values were expressed as mean and
standard deviation. (*; P<0,05; **: P<0.01)
FIGURE 2. (A) Hyperthyroidism eect on Body Weight (***: P<0.001), (B) on food intake (***: P<0.001), (C) on water intake (***: P<0.001). Values were expressed as mean
and standard deviation. (***: P<0.001)
A
A
B
B
C
C
TABLE II
Eects of hyperthyroidism on testicular MDA, GSH levels and
GSH.Px, CAT enzyme activity of the groups (Mean ± SD)
Groups
MDA
(nmol·g
-1
tissue)
GSH
(nmol·g
-1
tissue)
GSH·Px
(IU·g
-1
prot)
CAT
(k·g
-1
protein)
Control 38.45 ± 15.02 1.09 ± 0.15 26.32 ± 2.30 0.058 ± 0.013
Hyperthyroid 67.83 ± 23.18 1.52 ± 0.21 32.72 ± 2.18 0.045 ± 0.007
Signicant
P<0.01 P<0.001 P<0.001 P<0.05
L-Thyroxine induced Hyperthyroidism / Arkali et al. _________________________________________________________________________________

6



-1
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

P






6P
P
P


et al



etal

et al

et al]








TABLE III
Mean TSC diameter, germinal cell thickness and Johnsen Testicular
Score values in control and hyperthyroid groups (Mean ± SD)
Groups TSC Diameter (µm)
Germinal Cell
Thickness (µm)
Johnsen Testicular
Score
Control 273.33 ± 0.98 93.53 ± 0.46 9.62 ± 0.13
Hyperthyroid 261.20 ± 1.37 66.25 ± 0.86 8.36 ± 0.15
Signicant P<0.001 P<0.001 P<0.001
A B
FIGURE 3. (A) Normal histological appearance of testes in control group rats, (B)
Desquamation of germinal epithelial cells (arrow heads), vacuolar degeneration
(arrows) and hypoplasia (asterix) in hyperthyroidism group, HE 100×
TABLE IV
Eects of Hyperthyroidism on Spermatological Parameters (Mean ± SD)
Groups Motility (%)
Sperm concentration
(million/right cauda
epididymis)
Abnormal spermatozoon
rate (%)
Head Tail Total
Control 74,00 ± 9,66 121,20 ± 25,80 1,80 ± 0,78 2,20 ± 0,91 4,00 ± 1,05
Hyperthyroid 48,88 ± 14,52 94,00 ± 14,07 1,88 ± 0,78 2,66 ± 1,32 4,55 ± 1,33
Signicant
P<0.001 P<0.05 P>0.05 P>0.05 P>0.05
TABLE V
Eects of Hyperthyroidism on Absolute Reproductive Organ Weights (g)
(Mean ± SD)
Groups
Testes
(Right +Left )
2
Epididymis
(Right +Left)
2
Right Cauda
Epididymis
Seminal
Vesicles
Ventral
Prostate
Control 1,53 ± 0,17 0,67 ± 0,09 0,27 ± 0,02 1,71 ± 0,22 0,52 ± 0,11
Hyperthyroid 1,36 ± 0,11 0,53 ± 0,04 0,19 ± 0,02 1,17 ± 0,26 0,35 ± 0,11
Signicant
P<0.05 P<0.01 P<0.001 P<0.001 P<0.01
_____________________________________________________________________________Revista Cientifica, FCV-LUZ / Vol. XXXIV, rcfcv-e34436

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
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et alet al


et al



et al

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






PP
PP
PP
P
P
FIGURE 4. (A) Testes tissue PERK protein expression levels (**;P<0.01), (B) Testes tissue GRP78 protein expression levels (**;P<0.01), (C) Testes tissue ATF4 protein expression
levels (*;P<0.05), (D) Testes tissue Nrf2 protein expression levels (***; P<0.001), (E) Testes tissue HO–1 protein expression levels (*;P<0.05)
Control Hyperthyroid
0
50
100
150
200
PERK Protein Expression Levels
(% of control)
✱✱
Control Hyperthyroid
Control Hyperthyroid
0
50
100
150
200
250
GRP78 Protein Expression Levels
(% of control)
✱✱
Control Hyperthyroid
Control Hyperthyroid
0
50
100
150
200
250
ATF4 Protein Expression Levels
(% of control)
✱
Control Hyperthyroid
Control Hyperthyroid
0
50
100
150
200
Nrf2 Protein Expression Levels
(% of control)
✱✱✱
Control Hyperthyroid
Control Hyperthyroid
0
50
100
150
200
HO-1 Protein Expression Levels
(% of control)
Control Hyperthyroid
✱
A B C
D E
L-Thyroxine induced Hyperthyroidism / Arkali et al. _________________________________________________________________________________
6 of 8





CONCLUSIONS








Funding statement


Availability of data and materials


Conicts of interest

Author contributions
•
Gözde Arkali


• Şeyma Özer Kaya
• Songül Çeri̇baş
ı
•
Edanur Güler Ekmen

• Mesut Aksakal
• Mehmet Çay
BIBLIOGRAPHIC REFERENCES
 



_____________________________________________________________________________Revista Cientifica, FCV-LUZ / Vol. XXXIV, rcfcv-e34436
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
 


 



 





 



 


 


 


 


 









 

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 
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

 


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
 



 




 



L-Thyroxine induced Hyperthyroidism / Arkali et al. _________________________________________________________________________________
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 








 



 




 



 

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
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