TY - JOUR
T1 - Perfluorooctanesulfonic acid exposure altered hypothalamic metabolism and disturbed male fecundity
AU - Li, Zijie
AU - Lin, Ziyi
AU - Ji, Shuqin
AU - Lai, Keng Po
AU - Wan, Hin Ting
AU - Wong, Chris Kong Chu
AU - Li, Lei
N1 - Funding Information:
This work was supported by National Natural Science Foundation of China (NSFC), NSFC31971072 , NSFC32171154 , NSFC31471109 ; the Key Collaborative Research Program of the Alliance of International Science Organizations ( ANSO-CR-KP-2021-12 ); Guangdong Province Grants 2019A050510032 , 2017B030301017 ; CAS Key Laboratory of Brain Connectome and Manipulation 2019DP173024 ; China Shenzhen Science Technology and Innovative Commission (SZSTI), SZSTI JCYJ20180508152336419 ; SZSTI GJHZ20200731095406021 .
Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2022/10/20
Y1 - 2022/10/20
N2 - Previous studies have examined the effects of perfluorooctanesulfonic acid (PFOS) on disruption of the blood-testis barrier and spermatogenesis. Sertoli and Leydig cells were perturbed, resulting in a decrease in testosterone levels and sperm counts. However, the effects of PFOS on male fecundity are not limited to the testes. In this study, we demonstrated that oral PFOS exposure (1 μg/g BW and 5 μg/g BW) decreased the function of the Luteinizing hormone (LH)/Luteinizing hormone receptor (LHr) and decreased epididymal sperm motility. Consistently, testicular transcriptome analysis revealed that PFOS altered the expression of a cluster of genes associated with sperm motility and steroidogenesis. In mice exposed to PFOS, c-Fos immunostaining showed activation of the lateral septal nucleus (LS), paraventricular thalamus (PVT), locus coeruleus (LC), which are known to be related to anxiety-like behaviors. Metabolomic analyses of the hypothalamus revealed that exposure to PFOS perturbed the translation of proteins, as well as the biosynthesis of neurotransmitters and neuromodulators. Altogether, the activation of brain nuclei, shift of hypothalamic metabolome, and reduction of LH/LHr circuit resulted from PFOS exposure suggested the toxicant's systematic effects on male reproduction.
AB - Previous studies have examined the effects of perfluorooctanesulfonic acid (PFOS) on disruption of the blood-testis barrier and spermatogenesis. Sertoli and Leydig cells were perturbed, resulting in a decrease in testosterone levels and sperm counts. However, the effects of PFOS on male fecundity are not limited to the testes. In this study, we demonstrated that oral PFOS exposure (1 μg/g BW and 5 μg/g BW) decreased the function of the Luteinizing hormone (LH)/Luteinizing hormone receptor (LHr) and decreased epididymal sperm motility. Consistently, testicular transcriptome analysis revealed that PFOS altered the expression of a cluster of genes associated with sperm motility and steroidogenesis. In mice exposed to PFOS, c-Fos immunostaining showed activation of the lateral septal nucleus (LS), paraventricular thalamus (PVT), locus coeruleus (LC), which are known to be related to anxiety-like behaviors. Metabolomic analyses of the hypothalamus revealed that exposure to PFOS perturbed the translation of proteins, as well as the biosynthesis of neurotransmitters and neuromodulators. Altogether, the activation of brain nuclei, shift of hypothalamic metabolome, and reduction of LH/LHr circuit resulted from PFOS exposure suggested the toxicant's systematic effects on male reproduction.
KW - Hypothalamus
KW - Locus coeruleus
KW - Metabolome
KW - PFOS
KW - Transcriptome
UR - http://www.scopus.com/inward/record.url?scp=85133657292&partnerID=8YFLogxK
U2 - 10.1016/j.scitotenv.2022.156881
DO - 10.1016/j.scitotenv.2022.156881
M3 - Journal article
C2 - 35753445
AN - SCOPUS:85133657292
SN - 0048-9697
VL - 844
JO - Science of the Total Environment
JF - Science of the Total Environment
M1 - 156881
ER -