Subscriber access provided by UNIV OF DURHAM
Ecotoxicology and Human Environmental Health
Multigenerational Disruption of Thyroid Endocrine System in Marine Medaka after A Life-Cycle Exposure to Perfluorobutane Sulfonate (PFBS) Lianguo Chen, Chenyan Hu, Mirabelle M. P. Tsui, Teng Wan, Drew R. Peterson, Qipeng Shi, Paul K.S. Lam, Doris W. T. Au, James C.W. Lam, and Bingsheng Zhou Environ. Sci. Technol., Just Accepted Manuscript • DOI: 10.1021/acs.est.8b00700 • Publication Date (Web): 22 Mar 2018 Downloaded from http://pubs.acs.org on March 23, 2018
Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.
Page 1 of 34
Environmental Science & Technology
1
Multigenerational Disruption of Thyroid Endocrine System in Marine Medaka
2
after A Life-Cycle Exposure to Perfluorobutane Sulfonate (PFBS)
3 †,‡
, Chenyan Hu #, Mirabelle M. P. Tsui †, Teng Wan §, Drew R.
4
Lianguo Chen
5
Peterson §, Qipeng Shi ‡, Paul K. S. Lam †, Doris W. T. Au §, James C. W. Lam †,□,*,
6
Bingsheng Zhou ‡,*
7 8
†
9
Kowloon, Hong Kong SAR, China
State Key Laboratory in Marine Pollution, City University of Hong Kong,
10
‡
11
Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China
12
#
13
Technology, Wuhan 430072, China
14
§
15
SAR, China
16 17
□
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of
School of Chemistry and Environmental Engineering, Wuhan Institute of
Department of Chemistry, City University of Hong Kong, Kowloon, Hong Kong
Department of Science and Environmental Studies, The Education University of
Hong Kong, Hong Kong SAR, China
18 19 20 21 1
ACS Paragon Plus Environment
Environmental Science & Technology
22
* Corresponding authors:
23
Dr. James C.W. Lam
24
Tel: 0852-2948-8537
25
Fax: 0852-2948-7676
26
E-mail:
[email protected] 27 28
Dr. Bingsheng Zhou
29
Tel: +86 27 68780042
30
Fax: +86 27 68780123
31
E-mail:
[email protected] 2
ACS Paragon Plus Environment
Page 2 of 34
Page 3 of 34
Environmental Science & Technology
32
ABSTRACT
33
Accumulation of perfluorobutane sulfonate (PFBS) is frequently detected in biota,
34
raising concern about its ecological safety. However, hazardous effects of PFBS
35
remain largely unexplored, especially for endocrine disrupting potency. In the
36
present study, the multigenerational endocrine disrupting potential of PFBS was
37
investigated by exposing F0 marine medaka eggs to PFBS at different
38
concentrations (0, 1.0, 2.9 and 9.5 µg/L) until sexual maturity. The F1 and F2
39
generations were reared without continued exposure. Thyroidal disturbances were
40
examined in all three generations. PFBS exposure decreased the levels of
41
3,5,3’-triiodothyronine (T3) in F0 female blood, however, increased T3 or thyroxine
42
(T4) levels in F0 brains, which hyperthyroidism suppressed local transcription of
43
5'-deiodinase 2 (Dio2). Obviously decreased T3 was transferred to F1 eggs, although
44
the parental influences were reversed in F1 larvae. Delayed hatching was coupled
45
with elevated T3 levels in F1 larvae. F1 adult showed comparable symptoms of
46
thyroidal disruption with F0 adult. A slight recovery was noted in F2 generation,
47
although F2 larvae still exhibited thyroid disruption and synthesized excessive T4.
48
Our results suggested that the offspring suffered more severe dysfunction of
49
thyroidal axis albeit without direct exposure. This study provided the first molecular
50
insight about PFBS toxicology on thyroid, beneficial to human and environmental
51
risk assessment.
52 3
ACS Paragon Plus Environment
Environmental Science & Technology
Page 4 of 34
53
INTRODUCTION
54
Perfluoroalkyl substances (PFASs) belong to a large class of fully fluorinated
55
organic chemicals with varying carbon backbone length. Due to their unique
56
anti-wetting and surfactant properties, PFASs are widely used in diverse industrial
57
and commercial products, such as textiles, fire-fighting foams, electronics and
58
plastics
59
bioaccumulative nature, as well as potent adverse health effects
60
homolog, perfluorooctane sulfonate (PFOS), has been listed as a persistent organic
61
pollutant by the Stockholm Convention, which drives phasing-out of this substance
62
6,7
63
synthesized to meet the market demand 8.
1,2
. As a result of the increasing awareness of their persistent and 3,4,5
, the C8 PFAS
. As an alternative, the shorter chained (C4) perfluorobutane sulfonate (PFBS) is
64
PFBS is generally considered less bioaccumulative and less toxic compared to
65
PFOS because of its shorter chain length, which imparts characteristics of increased
66
solubility, rapid elimination and reduced affinity with critical receptors (e.g.,
67
peroxisome proliferator activated receptor α)
68
PFBS as a replacement for longer-chain PFASs has led to contamination of
69
environmental matrices. PFBS can be released directly into the environment or can
70
be formed via the degradation of substances based on perfluorobutanesulfonyl
71
fluoride
72
leachate of a landfill site at Singapore 13. A significant elevation in PFBS levels was
73
detected in cetacean samples from 2002 to 2014, resulting in a shift in accumulation
12
9–11
. However, increasing usage of
. For example, as high as 1.9 µg/L of PFBS was recently reported in the
4
ACS Paragon Plus Environment
Page 5 of 34
Environmental Science & Technology
74
from PFOS to PFBS 14. After exposure via contaminated drinking water, PFBS was
75
ubiquitously detected in the blood samples from children, women and men residing
76
in Arnsberg, Germany 15. In addition, chronic dietary exposure of adult quail also led
77
to concentration-dependent increases in PFBS accumulation in offspring eggs and
78
juveniles, indicating maternal transfer to the progeny 12.
79
Albeit to a lesser extent than PFOS, the presence of PFBS in the biota will 11,12,16
80
potentially impair the organismal health
. Furthermore, PFBS shares high
81
structural similarity with PFOS, while the latter has been found to disrupt the
82
functions of the thyroid endocrine system by competing with the plasma transporters
83
of thyroid hormones (THs), reducing circulating TH levels and disruption of the
84
regulatory mechanisms of the hypothalamus-pituitary-thyroid (HPT) axis
85
therefore reasonable to speculate that PFBS exerts disruptive effects on the thyroidal
86
axis, although currently there is no toxicological information available on the
87
endocrine disrupting effects of PFBS. This knowledge gap gives rise to uncertainty
88
about its ecological safety.
17–19
. It is
89
Therefore, in order to elucidate the thyroid endocrine disrupting potency of
90
PFBS and elicit the underlying mechanisms, the present study performed a life-cycle
91
exposure of F0 marine medaka (Oryzias melastigma), a model teleost used in marine
92
toxicology, to low concentrations of PFBS (0, 1, 3 and 10 µg/L). After parental
93
exposure from eggs till sexual maturity, the F1 and F2 generation offspring were
94
reared in PFBS-free seawater. Possible disturbances in the thyroidal axis across three 5
ACS Paragon Plus Environment
Environmental Science & Technology
Page 6 of 34
95
generations (F0, F1 and F2) were investigated to elucidate the multigenerational
96
thyroid disrupting potency of PFBS by analyzing the levels of THs and TH
97
transporters (thyroxine-binding globulin, TBG), HPT gene transcription patterns and
98
developmental defects.
99 100
MATERIALS AND METHODS
101
Chemicals
102
PFBS (purity >98.0%) was purchased from Tokyo Chemical Industry (Tokyo, Japan).
103
Stock
104
chromatography-grade dimethyl sulfoxide (DMSO; Sigma-Aldrich Corp., St. Louis,
105
MO, USA). QIAzol lysis reagent and SYBR Green PCR Kit were obtained from
106
Qiagen (Hilden, Germany). All other reagents used in this study were of analytic
107
grade.
solutions
of
PFBS
were
prepared
in
high-performance
liquid
108 109
Fish Maintenance and Exposure
110
Medaka (O. melastigma) embryos and adults were cultivated and exposed in a
111
semi-static system containing fully aerated, charcoal-filtered artificial seawater
112
(salinity: 25‰) under constant ambient temperature (24 ± 0.5°C) and a photoperiod
113
of 14 h light: 10 h dark, as previously described
114
were included for each exposure group of PFBS (0, 1, 3 and 10 µg/L; n = 3).
115
Approximately 150 embryos were randomly distributed in each glass beaker
20
. Briefly, three replicate beakers
6
ACS Paragon Plus Environment
Page 7 of 34
Environmental Science & Technology
116
containing 100-mL PFBS-spiked exposure medium; the control group received
117
DMSO only (
