title: Perinatal sulfamonomethoxine exposure influences physiological and behavioral responses and the brain mTOR pathway in mouse offspring.
abstract: Sulfamonomethoxine (SMM) is widely used in the veterinary field in China. Although some clinical surveys have revealed that sulfonamide antibiotics cause adverse nervous system symptoms, the related mechanisms of maternal SMM exposure on the neurobehavioral development of offspring remain unclear. Here, we investigated the effects of perinatal SMM exposure on the physiological and behavioral responses of pubertal offspring mice and the underlying mechanisms. We randomly allocated pregnant mice into the groups treated with SMM at different doses and the saline-treated groups. Maternal mice were orally administered SMM daily from gestational day 1 to postpartum day 21. On postnatal day (PND) 22, the parameters of growth, endocrine hormones, and brain amino acid composition were assessed, as well as the brain transcript levels of key genes involved in the mammalian target of rapamycin (mTOR) signaling pathway. From PND 50 to 55, a battery of behavioral tests relevant to anxiety and memory were then administered. Analysis of the results indicated that the pups, particularly the pubertal female offspring, showed anxiety-like behavior. Moreover, the pubertal offspring showed cognitive impairments and fat accumulation. Furthermore, the relative mRNA expression of genes involved in the mTOR signaling pathway in females on PND 22 was elevated, whereas the expression of N-methyl-d-aspartate receptor 2B (NR2B) was reduced. Together, the results showed that perinatal SMM exposure perturbs neuroendocrine functions, and further alters gene expression in the mTOR pathway and NR2B gene expression early in life, which may contribute to brain dysfunction in pubertal life.
authors.affiliation: 1 Department of Nutrition and Food Hygiene, School of Public Health, Anhui Medical University, Hefei, People's Republic of China.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: 2 Lujiang County Center for Disease Control and Prevention, Lujiang County, People's Republic of China.
authors.forename: D
authors.initials: D
authors.lastname: Zhang
authors.affiliation: 1 Department of Nutrition and Food Hygiene, School of Public Health, Anhui Medical University, Hefei, People's Republic of China.
authors.forename: Kai-Yong
authors.initials: KY
authors.lastname: Liu
authors.affiliation: 3 Department of Public Health Inspection and Quarantine Science, School of Public Health, Anhui Medical University, Hefei, People's Republic of China.
authors.forename: Ye-Hao
authors.initials: YH
authors.lastname: Liu
authors.affiliation: 3 Department of Public Health Inspection and Quarantine Science, School of Public Health, Anhui Medical University, Hefei, People's Republic of China.
authors.forename: J
authors.initials: J
authors.lastname: Sheng
authors.affiliation: 3 Department of Public Health Inspection and Quarantine Science, School of Public Health, Anhui Medical University, Hefei, People's Republic of China.
authors.forename: Zhong-Xiu
authors.initials: ZX
authors.lastname: Jin
authors.affiliation: 1 Department of Nutrition and Food Hygiene, School of Public Health, Anhui Medical University, Hefei, People's Republic of China.
authors.forename: Su-Fang
authors.initials: SF
authors.lastname: Wang
authors.affiliation: 1 Department of Nutrition and Food Hygiene, School of Public Health, Anhui Medical University, Hefei, People's Republic of China.
authors.forename: Qing-Li
authors.initials: QL
authors.lastname: Bo
authors.affiliation: 1 Department of Nutrition and Food Hygiene, School of Public Health, Anhui Medical University, Hefei, People's Republic of China.
authors.forename: Jia-Jia
authors.initials: JJ
authors.lastname: Wang
authors.affiliation: 4 Fujian Provincial Key Laboratory of Preventive Veterinary Medicine and Veterinary Biotechnology, College of Life Science, Long Yan University, Longyan, People's Republic of China.
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Yin
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006728:Hormones / Q000097:blood; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000235:genetics; D013422:Sulfamonomethoxine / Q000633:toxicity*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D006728:Hormones; D012333:RNA, Messenger; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D013422:Sulfamonomethoxine
keywords: Neurotoxicity; anxiety; perinatal period; spatial cognition; sulfamonomethoxine