Aspartame Intake Delayed Puberty Onset in Female Offspring Rats and Girls

• Published in: Molecular nutrition & food research Vol. 68; no. 5; pp. e2300270 - n/a
• Main Authors: Lin, Chia‐Yuan, Nguyen, Nam Nhat, Tsai, Wan‐Ling, Hsieh, Rong‐Hong, Wu, Hung‐Tsung, Chen, Yang‐Ching
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01-03-2024
• Subjects: Animals; Aspartame; Aspartame - adverse effects; Aspartame - metabolism; Children; delayed puberty; Estrogens; Female; female offspring rat; Females; Gonadotropin-releasing hormone; Gonadotropin-Releasing Hormone - genetics; Gonadotropins; gut microbiota; HPG axis; Humans; Hypothalamus; Hypothalamus - metabolism; Intestinal microflora; Kisspeptins - metabolism; Kisspeptins - pharmacology; Luteinizing hormone; mRNA; Offspring; Pituitary; Pituitary (anterior); Prolongation; Puberty; Puberty, Delayed - metabolism; Rats; Rats, Sprague-Dawley; Risk reduction; RNA, Messenger - metabolism; Sexual Maturation - physiology; female offspring rat; HPG axis; delayed puberty; aspartame; gut microbiota
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.202300270

Scope
The disturbance of the hypothalamic–pituitary‐gonadal (HPG) axis, gut microbiota (GM) community, and short‐chain fatty acids (SCFAs) is a triggering factor for pubertal onset. The study investigates the effects of the long‐term intake of aspartame on puberty and GM in animals and humans.
Methods and results
Aspartame‐fed female offspring rats result in vaginal opening time prolongation, serum estrogen reduction, and serum luteinizing hormone elevation. , 60 mg kg−1 aspartame treatment decreases the mRNA levels of gonadotropin‐releasing hormone (GnRH), Kiss1, and G protein‐coupled receptor 54 (GPR54), increases the mRNA level of RFamide‐related peptide‐3 (RFRP‐3), and decreases the expression of GnRH neurons in the hypothalamus. Significant differences in relative bacterial abundance at the genus levels and decreased fecal SCFA levels are noted by 60 mg kg−1 aspartame treatment. Among which, Escherichia–Shigella is negatively correlated with several SCFAs. In girls, high‐dose aspartame consumption decreases the risk of precocious puberty.
Conclusions
Aspartame reduces the chance of puberty occurring earlier than usual in female offspring and girls. Particularly, 60 mg kg−1 aspartame‐fed female offspring delays pubertal onset through the dysregulation of HPG axis and GM composition by inhibiting the Kiss1/GPR54 system and inducing the RFRP‐3. An acceptable dose of aspartame should be recommended during childhood.
Aspartame, a non‐nutritive sweetener, delayed pubertal onset through the inhibition of Kiss1/GPR54 system, the dysregulation of hypothalamic‐pituitary‐gonadal axis, and the alteration of gut microbiota composition in female offsprng rats and girls.