Effects of Daily Exposure to Saccharin and Sucrose on Testicular Biologic Functions in Mice.
Saccharin sodium consumption is considered safe and beneficial, owing to its very intense sweetness without any associated calories, but supporting scientific data remain sparse and controversial. Herein, we demonstrate that dose-response relationships existed with regard to administration of saccharin or sucrose to mice for 35 days, and this association involved testis-expressed sweet-tasting molecules (taste receptor type 1 subunit 3 [T1R3]; G protein alpha-gustducin [Galpha]). Mouse body weights and testis weights in middle- and low-dose saccharin-treated groups were increased with up-expressions of molecules involved in testicular sweet taste and steroidogenic (middle saccharin: steroidogenic acute regulatory protein [StAR]; P450 cholesterol side-chain cleavage enzyme [CYP11A1]; 17-alpha-hydroxylase/C17,20-lyase [CYP17A1]; low saccharin: StAR). Moreover, a high-dose saccharin-related decline in reproductive hormone levels and injuries to testis and sperm were observed to be associated with suppression of testicular T1R3 and Galpha, as well as steroidogenic-related factors (StAR; 3-beta-hydroxysteroid dehydrogenase [3-beta-HSD]; CYP11A1; CYP17A1; 17-beta-hydroxysteroid dehydrogenase [17-beta-HSD]), and activation of cleaved caspase-3. However, abnormalities of the testis and sperm in high- and middle-dose sucrose-exposed mice were related to the increased-cleaved caspase-3, but independent of T1R3 and/or Galpha. Collectively, our results clearly suggest that saccharin-induced physiologic effects on testis are associated with testicular T1R3 and Galpha, which differed from sucrose. We hence call for a reassessment of the excessive use of sweeteners in daily life, especially artificial ones, considering their potential side effects.
Laboratory of Animal Reproduction, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.
Ting
T
Gong
Laboratory of Animal Reproduction, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.
Quan-Wei
QW
Wei
Laboratory of Animal Reproduction, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.
Da-Gan
DG
Mao
Laboratory of Veterinary Physiology, Department of Veterinary Medicine, Tokyo University of Agriculture and Technology, Tokyo, Japan.
Kentaro
K
Nagaoka
Laboratory of Veterinary Physiology, Department of Veterinary Medicine, Tokyo University of Agriculture and Technology, Tokyo, Japan.
Gen
G
Watanabe
Laboratory of Animal Reproduction, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.|Laboratory of Veterinary Physiology, Department of Veterinary Medicine, Tokyo University of Agriculture and Technology, Tokyo, Japan.
Kazuyoshi
K
Taya
Laboratory of Animal Reproduction, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China fxshi@njau.edu.cn.
Fang-Xiong
FX
Shi
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D048430:Cell Shape / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D004958:Estradiol / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D010750:Phosphoproteins / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D012439:Saccharin / Q000494:pharmacology*; D013081:Sperm Motility / Q000187:drug effects; D013094:Spermatozoa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013395:Sucrose / Q000494:pharmacology*; D013549:Sweetening Agents / Q000494:pharmacology*; D013737:Testis / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D015293:Transducin / Q000378:metabolism; D014280:Triglycerides / Q000097:blood; D000098682:Steroidogenic Acute Regulatory Protein
D001786:Blood Glucose; D010750:Phosphoproteins; D043562:Receptors, G-Protein-Coupled; D013549:Sweetening Agents; D014280:Triglycerides; D000098682:Steroidogenic Acute Regulatory Protein; C431926:taste receptors, type 1; C075192:gustducin; D013739:Testosterone; D004958:Estradiol; D013395:Sucrose; D007986:Luteinizing Hormone; D002784:Cholesterol; D002786:Cholesterol Side-Chain Cleavage Enzyme; D053148:Caspase 3; D015293:Transducin; D012439:Saccharin
saccharin; sperm; steroid hormones; sucrose; testis