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Citation
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HERO ID
6505878
Reference Type
Journal Article
Title
Exposure of female mice to perfluorooctanoic acid suppresses hypothalamic kisspeptin-reproductive endocrine system through enhanced hepatic fibroblast growth factor 21 synthesis, leading to ovulation failure and prolonged dioestrus
Author(s)
Zhang, Y; Cao, X; Chen, L; Qin, Y; Xu, Y; Tian, Y; Chen, L
Year
2020
Is Peer Reviewed?
Yes
Journal
Journal of Neuroendocrinology
ISSN:
0953-8194
EISSN:
1365-2826
Publisher
WILEY
Location
HOBOKEN
Volume
32
Issue
5
Page Numbers
e12848
Language
English
PMID
32307816
DOI
10.1111/jne.12848
Web of Science Id
WOS:000526577900001
Abstract
Perfluorooctanoic acid (PFOA) is widely used in household applications. High-dose exposure to PFOA has been associated with increased risks of infertility and premature ovarian insufficiency in woman. PFOA can alter hepatic gene expression by activating peroxisome proliferator-activated receptor α (PPARα). The present study investigated whether exposure to PFOA via PPARα activation alters the synthesis of hepatic fibroblast growth factor 21 (FGF21) to disturb female neuroendocrine and reproductive function. In the present study, we show that the oral administration of PFOA (2 or 5 mg kg-1 ) in adult female mice (PFOA mice) caused prolonged dioestrous, a reduction in the number of corpora lutea and decreased levels of hypothalamic gonadotrophin-releasing hormone, serum progesterone and luteinising hormone (LH). Exposure to PFOA decreased the expression of vasopressin in the suprachiasmatic nucleus (SCN) and kisspeptin in the anteroventral periventricular nucleus (AVPV) with deficits in preovulation or oestrogen-induced LH surge. PFOA via activation of PPARα increased dose-dependently hepatic FGF21 expression, leading to elevated serum and hypothalamic FGF21 concentrations. Treatment of PFOA mice with the PPARα antagonist GW6471 or the FGF21 inhibitor PD173074 rescued SCN vasopressin and AVPV-kisspeptin expression. Either administration of GW6471 and PD173074 or treatment with vasopressin and the G protein coupled receptor 54 agonist kisspeptin-10 in PFOA-mice was able to recover the regular oestrous cycle, ovulation ability, LH surge production and reproductive hormone levels. The present study provides in vivo evidence that exposure to PFOA (≥2 mg kg-1 ) in mice causes down-regulation of the kisspeptin-reproductive endocrine system by enhancing PPARα-mediated hepatic FGF21 expression. The liver-brain reproductive endocrine disorder caused by PFOA exposure may lead to prolonged dioestrous and ovulation failure.
Tags
•
PFAS 150
Missing 2021 searches
Not prioritized for screening
•
PFHxS
•
PFOA (335-67-1) and PFOS (1763-23-1)
LitSearch: Feb 2019 - May 2020
PubMed
WoS
Literature Search Update (Apr 2019 - Sep 2020)
PubMed
WOS
•
PFOA and PFOS OW MCLG Approaches
Cited in White Papers
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