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Perinatal antibiotics exposure causes increase in serum 5-hydroxytryptamine level as well as changes in behavior and gastrointestinal motility in the male offspring in mice

ZOU Yu-Yao, WU Xiao-Yu, SHU Lan, JI Pei-Lin, GONG Hua-Shan, RONG Wei-Fang^*

Department of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

Abstract

The current study was aimed to investigate the potential effects of perinatal exposure to therapeutic dose of penicillin and cefixime on the cognitive behaviors, gastrointestinal (GI) motility and serum 5-hydroxytryptamine (5-HT) level in the offspring. Pregnant rats were continuously treated with cefixime or penicillin in the period between 1 week before and 1 week after labor. Behavior tests, including social preference, self-grooming and elevated plus maze tests, and intestinal motility tests were carried out on the offspring at age of 4 to 10 weeks. Serum 5-HT levels were detected with ELISA, and potassium/sodium hyperpolarization activated cyclic nucleotide-gated channel 2 (HCN2) and tryptophan hydroxylase 1 (TPH1) expression levels in colon epithelium of offspring were detected by Western blot and RT-qPCR. The results showed that, compared with the naive group, cefixime increased social behavior in the female offspring, but did not affect the male offspring. Compared with the naive group, cefixime significantly decreased colonic and intestinal transits, and increased cecum net weight and standardized cecum net weight in the male offspring, but did not affect the female offspring. The serum 5-HT levels in the male offspring, rather than the female offspring, in cefixime and penicillin groups were significantly increased compared with that in the naive group. The protein expression level of HCN2 in colon epithelium of the offspring in cefixime group was significantly down-regulated, and the TPH1 expression level was not significantly changed, compared with that in the naive group. These results suggest that perinatal antibiotics exposure may affect neural development and GI functions of the offspring, and the mechanism may involve peripheral 5-HT and gender-dependent factor.

Key words: perinatal; cefixime; antibiotics; behavior; 5-hydroxytryptamine; gastrointestinal motility

Received: 2019-10-31　　Accepted: 2020-03-19

Corresponding author: 戎伟芳　　E-mail: weifangrong@hotmail.com

DOI: 10.13294/j.aps.2020.0042

Citing This Article：

ZOU Yu-Yao, WU Xiao-Yu, SHU Lan, JI Pei-Lin, GONG Hua-Shan, RONG Wei-Fang. Perinatal antibiotics exposure causes increase in serum 5-hydroxytryptamine level as well as changes in behavior and gastrointestinal motility in the male offspring in mice. Acta Physiol Sin 2020; 72 (3): 285-298 (in Chinese with English abstract).