Accumulation of dietary glycotoxins in the reproductive system of normal female rats.
The aim of the present study was to investigate whether dietary advanced glycation end-products (AGEs) can be detected in the ovarian tissue of normal female rats and whether they can affect their metabolic or hormonal profile. Sixty normal rats (20 animals in each group) were randomly assigned to regular diet, either high (H-AGE) or low (L-AGE) in AGE content for 6 months. H-AGE rats demonstrated higher levels of fasting glucose (P < 0.001), insulin (P < 0.069), and serum AGEs (P < 0.001) than control and L-AGE rats. Additionally, the H-AGE group showed increased AGE localization in the theca interna cells of the ovarian tissue compared to control/L-AGE rats (P = 0.003). Furthermore, increased receptor for AGE (RAGE) staining was also observed in granulosa cells compared to control/L-AGE samples (P = 0.038). In the H-AGE group, plasma testosterone was higher than in control rats (P < 0.001) and in the L-AGE group (P < 0.001). However, H-AGE rats did not exhibit higher body weight compared with normal (P = 0.118) and L-AGE-fed rats (P = 0.35). These results demonstrate for the first time that administration of high AGE diet in female rats for a prolonged period is associated with increased deposition of AGEs in the theca cells and of RAGE in the granulosa and theca interna cells of the ovarian tissue compared with the corresponding ovarian compartments of the control and L-AGE-fed animals. The metabolic alterations in conjuction with the increased deposition in ovarian tissues of dietary glycotoxins and elevated levels of testosterone in H-AGE-fed animals compared to the controls suggest an impact of environmental factors on ovarian tissue and these findings need further exploration.
Diamanti-Kandarakis
Evanthia
E
First Department of Internal Medicine, Endocrine section, Medical School, University of Athens, Athens, Greece.
Piperi
Christina
C
Korkolopoulou
Penelope
P
Kandaraki
Eleni
E
Levidou
Georgia
G
Papalois
Apostolos
A
Patsouris
Efstratios
E
Papavassiliou
Athanasios G
AG
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D004032:Diet; D005260:Female; D017127:Glycation End Products, Advanced / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D006107:Granulosa Cells / Q000378:metabolism; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood; D009929:Organ Size; D010053:Ovary / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D013799:Theca Cells / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation
D001786:Blood Glucose; D017127:Glycation End Products, Advanced; D007328:Insulin; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D013739:Testosterone
Diabetes. 2002 Jul;51(7):2082-9
12086936
Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15596-601
12429856
Crit Rev Food Sci Nutr. 1989;28(3):211-48
2669832
Atherosclerosis. 2002 Aug;163(2):303-11
12052477
J Am Soc Nephrol. 2003 Mar;14(3):728-31
12595509
Ann N Y Acad Sci. 2002 Apr;959:360-7
11976210
Diabetes Metab Res Rev. 2002 May-Jun;18(3):224-37
12112941
Clin Endocrinol (Oxf). 2007 Jan;66(1):103-9
17201808
Lab Invest. 1994 Feb;70(2):138-51
8139257
J Clin Invest. 1993 Jun;91(6):2470-8
8514859
J Intern Med. 2002 Feb;251(2):87-101
11905595
J Am Diet Assoc. 2004 Aug;104(8):1287-91
15281050
Diabetes. 2005 Aug;54(8):2314-9
16046296
Clin Endocrinol (Oxf). 2005 Jan;62(1):37-43
15638868
Kidney Int. 1995 Aug;48(2):517-26
7564121
Metabolism. 2006 Apr;55(4):494-500
16546480
Histochem Cell Biol. 2007 Jun;127(6):581-9
17205306
Proc Natl Acad Sci U S A. 1997 Jun 10;94(12):6474-9
9177242
Prog Food Nutr Sci. 1981;5(1-6):243-56
7034050
Mol Med. 2002 Jul;8(7):337-46
12393931