Possible role of serotonin and neuropeptide Y on the disruption of the reproductive axis activity by perfluorooctane sulfonate

López-Doval, S.; Salgado, Renato M.; Fernández-Pérez, B; Lafuente, A.

doi:10.1016/j.toxlet.2015.01.012

Cited by 27 publications

(20 citation statements)

References 85 publications

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“…For example, PFOS increased the level of serotonin in different regions of the rat brain [55] and impaired the dopaminergic system in both mice and zebrafish [22,27]. Moreover, it has been shown that PFOS exposure upregulated crhb , which is a marker of the stress response [56].…”

Section: Discussionmentioning

confidence: 99%

A Mixture of Persistent Organic Pollutants and Perfluorooctanesulfonic Acid Induces Similar Behavioural Responses, but Different Gene Expression Profiles in Zebrafish Larvae

Khezri

Fraser

Nourizadeh-Lillabadi

et al. 2017

IJMS

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Persistent organic pollutants (POPs) are widespread in the environment and some may be neurotoxic. As we are exposed to complex mixtures of POPs, we aimed to investigate how a POP mixture based on Scandinavian human blood data affects behaviour and neurodevelopment during early life in zebrafish. Embryos/larvae were exposed to a series of sub-lethal doses and behaviour was examined at 96 h post fertilization (hpf). In order to determine the sensitivity window to the POP mixture, exposure models of 6 to 48 and 48 to 96 hpf were used. The expression of genes related to neurological development was also assessed. Results indicate that the POP mixture increases the swimming speed of larval zebrafish following exposure between 48 to 96 hpf. This behavioural effect was associated with the perfluorinated compounds, and more specifically with perfluorooctanesulfonic acid (PFOS). The expression of genes related to the stress response, GABAergic, dopaminergic, histaminergic, serotoninergic, cholinergic systems and neuronal maintenance, were altered. However, there was little overlap in those genes that were significantly altered by the POP mixture and PFOS. Our findings show that the POP mixture and PFOS can have a similar effect on behaviour, yet alter the expression of genes relevant to neurological development differently.

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Section: Discussionmentioning

confidence: 99%

A Mixture of Persistent Organic Pollutants and Perfluorooctanesulfonic Acid Induces Similar Behavioural Responses, but Different Gene Expression Profiles in Zebrafish Larvae

Khezri

Fraser

Nourizadeh-Lillabadi

et al. 2017

IJMS

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“…The lowest detectable levels for LH, P 4 and E 2 were 0.15 IU L ‐1 , 0.47 ng mL ‐1 and 4.45 pg mL ‐1 . The hypothalamic GnRH concentration was examined using an ELISA kit (Uscn Life Science Inc.) as described previously 33 . The intra‐ and inter‐assay coefficients of variation for GnRH were 5.9% and 8.2%, respectively.…”

Section: Methodsmentioning

confidence: 99%

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

Zhang

Cao

Chen

et al. 2020

J Neuroendocrinology

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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. K E Y W O R D Sfibroblast growth factor 21, kisspeptin neurones, ovulation, perfluorooctanoic acid, peroxisome proliferator-activated receptor α 2 of 16 | ZHANG et Al.

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“…Taking into account that estradiol stimulates prolactin release within the hypothalamus and at the pituitary gland level (Freeman et al, 2000), we can think that PFOS would inhibit prolactin secretion by suppressing estradiol release, which could affect different neuromodulators in the anterior hypothalamus and the sensitivity of lactotroph cells to these modulators. However, norepinephrine and neuropeptide Y do not seem to be involved in the inhibition of prolactin secretion by PFOS because the changes observed in these neuromodulators after PFOS exposure L opez-Doval et al, 2015) do not correlate with the low serum prolactin levels observed in PFOStreated animals.…”

Section: Discussionmentioning

confidence: 94%

“…In fact, PFOS inhibits the reproductive axis function (L opez-Doval et al, 2014(L opez-Doval et al, , 2015 and this effect could be mediated by the increased concentration of dopamine, observed in the anterior hypothalamus after PFOS administration. Likewise, the diminution of the intraneuronal dopamine metabolism reported by the PFOStreated animals might be due to changes in the activity of the dopamine transporter because this transporter is regulated by estrogens and PFOS can alter estrogen secretion (Fang et al, 2012;Du et al, 2013;Lafuente et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…This fact would increase and/or explain, at least in part, some toxicity effects of this perfluorinated compound. Among these diseases, we can note reproductive pathologies (L opez-Doval et al, 2014(L opez-Doval et al, , 2015Watanabe et al, 2014), a disruption of the development and regulation of the stress response (Gunn et al, 2015), alterations in the corticotropin-releasing hormone (Tran et al, 1999), as well as desynchronization of the circadian rhythms (Kalsbeek et al, 2000), insomnia (Plante et al, 2012), and changes in the thermoregulation (Jha and Mallick, 2009).…”

Section: Discussionmentioning

confidence: 99%

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Initial study on the possible mechanisms involved in the effects of high doses of perfluorooctane sulfonate (PFOS) on prolactin secretion

Salgado

Pereiro

López-Doval

et al. 2015

Food and Chemical Toxicology

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Possible role of serotonin and neuropeptide Y on the disruption of the reproductive axis activity by perfluorooctane sulfonate

Cited by 27 publications

References 85 publications

A Mixture of Persistent Organic Pollutants and Perfluorooctanesulfonic Acid Induces Similar Behavioural Responses, but Different Gene Expression Profiles in Zebrafish Larvae

A Mixture of Persistent Organic Pollutants and Perfluorooctanesulfonic Acid Induces Similar Behavioural Responses, but Different Gene Expression Profiles in Zebrafish Larvae

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

Initial study on the possible mechanisms involved in the effects of high doses of perfluorooctane sulfonate (PFOS) on prolactin secretion

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