PowerPoint PresentationUNC-Chapel Hill
PFAS: Integrating Science and Solutions in NC
Do PFAS in drinking water pose a risk to pregnant women and could they affect the health and function of her placenta?
Do PFAS in drinking water pose a risk to pregnant women and could they affect the health and function of her placenta?
PFAS
What are the levels of PFAS in the placenta??
What is the effect of PFAS on placental health and function?
Human Cells
PFPeS PFHxS PFHpS PFOS PFHxA PFOA PFNA PFDA PFUnA PFTriA PFTA Chain length 5 6 7 8 6 8 9 10 11 13 14
%> LOD 31.1 74.6 54.9 99.2 1.6 27.0 21.3 39.3 49.2 29.5 6.6 Maximum 0.035 0.446 0.063 4.87 5.87 1.23 0.494 0.465 0.24 0.336 0.111 Minimum < 0.005 < 0.033 < 0.008 < 0.001 < 1.32 < 0.290 < 0.148 < 0.030 < 0.033 < 0.050 < 0.049 Median < 0.005 0.067 0.009 0.48 < 1.45 < 0.315 < 0.163 < 0.031 < 0.031 < 0.057 < 0.054
n 122 122 122 122 122 122 122 122 122 122 122
What are the levels of PFAS in the placenta?
PFAS results are presented as ng/g wet weight
• 122 placentas from high-risk pregnancies at UNC Hospitals • Pre-Term Birth cohort • Monitored for a total of 26 PFAS • Including GenX, Nafion BP2 previously seen in Wilmington serum • 11 legacy PFAS found above limit of detection (LOD)
Matched IDs
PFAS Sample ID
PFAS Sample ID
Cannot report: interfering peaks or contaminantion in Mass Spec line
PFBA
PFHpA
Extra
PFHxS2
PFOS1
PFHpS
PFUnA
PFOA
PFNA
PFDA1
PFPeS
PFTriA
PFTA
PFHxA
71
0.072
1.13
0.014
< 0.038
< 0.330
< 0.169
< 0.033
0.007
< 0.060
< 0.056
1.91
23
0.072
0.774
0.012
0.075
1.12
0.381
0.08
0.009
0.065
< 0.057
5.87
9
0.264
1.11
0.025
< 0.031
1.01
0.357
0.137
0.006
< 0.050
< 0.046
< 1.24
213
0.047
0.551
0.009
0.071
< 0.290
< 0.148
< 0.029
< 0.005
0.056
< 0.049
< 1.31
38
0.377
1.91
0.043
0.046
1.23
0.494
0.25
0.012
< 0.053
< 0.049
< 1.31
194
0.064
0.166
< 0.008
< 0.033
< 0.292
< 0.149
< 0.030
0.005
< 0.053
< 0.049
< 1.32
91
0.137
0.372
< 0.008
< 0.033
< 0.292
< 0.149
< 0.030
0.007
< 0.053
< 0.049
< 1.32
50
0.064
0.259
< 0.008
< 0.033
< 0.292
< 0.149
< 0.030
< 0.005
< 0.053
< 0.049
< 1.32
100
0.044
1.72
0.009
0.067
< 0.296
< 0.152
0.226
0.009
0.077
0.056
< 1.34
73
0.14
1.07
0.013
0.1
< 0.295
0.211
0.053
< 0.005
0.139
0.071
< 1.34
79
0.241
0.809
0.019
0.039
< 0.296
< 0.151
0.034
< 0.005
0.057
< 0.050
< 1.34
177
0.124
0.569
0.01
0.057
< 0.296
0.173
0.082
0.005
0.071
< 0.050
< 1.34
60
0.14
0.583
0.008
< 0.034
0.33
0.243
0.069
< 0.005
< 0.054
< 0.050
< 1.34
160
< 0.033
0.211
< 0.008
< 0.034
0.55
< 0.152
< 0.030
0.005
< 0.054
< 0.050
< 1.35
67
0.053
0.668
< 0.008
0.036
< 0.299
< 0.153
< 0.030
< 0.005
0.058
< 0.051
< 1.35
21
0.04
0.381
0.009
< 0.034
< 0.300
< 0.153
< 0.030
< 0.005
0.06
< 0.051
< 1.36
240
0.041
< 0.001
< 0.008
0.04
< 0.300
< 0.154
< 0.030
< 0.005
0.062
< 0.051
< 1.36
120
0.051
0.49
0.009
0.034
< 0.300
< 0.154
< 0.030
< 0.005
0.065
< 0.051
< 1.36
119
0.044
0.205
< 0.009
0.038
< 0.301
< 0.154
< 0.031
< 0.005
0.065
< 0.051
< 1.36
202
0.047
1.02
0.011
0.037
< 0.300
0.187
0.088
< 0.005
0.086
< 0.051
< 1.36
237
< 0.033
0.199
< 0.009
0.051
< 0.301
< 0.154
< 0.031
< 0.005
0.087
< 0.051
< 1.36
103
0.04
0.164
< 0.008
< 0.034
0.857
< 0.153
< 0.030
< 0.005
< 0.055
< 0.051
< 1.36
98
0.121
0.351
< 0.009
< 0.034
< 0.301
< 0.154
< 0.030
< 0.005
< 0.055
< 0.051
< 1.36
190
0.081
0.317
< 0.009
< 0.034
< 0.302
< 0.155
< 0.031
< 0.005
< 0.055
< 0.051
< 1.37
121
< 0.033
0.31
< 0.009
0.105
0.936
< 0.156
0.04
0.005
0.336
0.111
< 1.38
191
< 0.033
0.136
< 0.009
0.043
< 0.304
< 0.156
< 0.031
< 0.005
< 0.056
< 0.051
< 1.38
78
0.043
0.499
< 0.009
0.042
< 0.305
0.184
0.042
< 0.005
< 0.056
< 0.052
< 1.38
42
0.13
0.989
< 0.009
0.04
< 0.305
< 0.156
< 0.031
< 0.005
< 0.056
< 0.052
< 1.38
218
0.116
0.196
0.021
< 0.035
0.31
< 0.157
0.148
0.01
< 0.056
< 0.052
< 1.39
75
0.058
0.978
0.015
< 0.035
< 0.307
< 0.157
< 0.031
0.016
< 0.056
< 0.052
< 1.39
64
0.256
0.373
0.016
0.036
0.613
< 0.157
0.033
0.035
< 0.056
< 0.052
< 1.39
61
0.332
0.847
0.01
0.039
0.56
0.27
0.168
< 0.005
< 0.056
< 0.052
< 1.39
226
0.116
1.06
0.012
0.217
< 0.307
0.192
0.364
< 0.005
< 0.056
< 0.052
< 1.39
62
< 0.034
0.151
< 0.009
< 0.035
0.573
< 0.158
< 0.031
0.006
< 0.056
< 0.052
< 1.40
157
0.144
0.006
0.009
< 0.035
< 0.309
< 0.158
< 0.031
0.006
< 0.057
< 0.052
< 1.40
5
0.363
0.836
0.025
< 0.035
0.358
< 0.158
< 0.031
0.012
< 0.057
< 0.052
< 1.40
234
0.047
0.239
< 0.009
< 0.035
< 0.309
0.193
0.075
< 0.005
< 0.057
< 0.052
< 1.40
74
< 0.034
0.249
< 0.009
< 0.035
< 0.310
< 0.159
< 0.031
< 0.005
< 0.057
< 0.052
< 1.40
8
0.036
0.613
0.011
0.076
< 0.312
< 0.160
0.082
< 0.005
0.072
< 0.053
< 1.41
93
< 0.034
1.82
< 0.009
0.112
0.998
0.249
0.225
< 0.005
0.095
< 0.053
< 1.41
83R
0.093
1.5
0.009
0.24
0.35
0.235
0.465
0.009
0.111
< 0.053
< 1.41
220
0.191
0.791
0.018
0.043
0.953
0.232
0.092
< 0.005
< 0.057
< 0.053
< 1.41
150
< 0.034
0.036
< 0.009
< 0.035
< 0.311
< 0.159
< 0.032
< 0.005
< 0.057
< 0.053
< 1.41
186
0.266
0.662
0.025
0.041
0.549
0.309
0.213
0.01
< 0.057
< 0.053
< 1.42
106
0.085
0.862
0.01
0.045
0.674
< 0.160
< 0.032
< 0.005
< 0.057
< 0.053
< 1.42
232
0.071
1.26
0.009
0.094
< 0.316
< 0.162
0.076
0.006
< 0.058
< 0.053
< 1.43
131
< 0.034
0.528
< 0.009
0.048
< 0.315
0.168
< 0.032
0.006
< 0.058
< 0.053
< 1.43
77R
0.229
0.01
< 0.009
< 0.036
0.356
< 0.162
< 0.032
0.009
< 0.058
< 0.053
< 1.43
68R
0.036
0.304
< 0.009
< 0.036
< 0.316
< 0.162
< 0.032
< 0.005
< 0.058
< 0.054
< 1.43
2
0.056
0.432
0.009
< 0.036
< 0.318
< 0.163
0.048
< 0.005
< 0.058
< 0.054
< 1.44
69
0.257
1.18
0.01
< 0.036
< 0.318
< 0.163
0.057
< 0.005
< 0.058
< 0.054
< 1.44
52
< 0.035
0.141
< 0.009
< 0.036
< 0.318
< 0.163
< 0.032
< 0.005
< 0.058
< 0.054
< 1.44
139
0.117
0.785
0.016
0.043
0.693
< 0.164
0.157
< 0.005
0.072
< 0.054
< 1.45
97
< 0.035
0.475
0.011
< 0.036
< 0.319
< 0.163
< 0.032
0.006
< 0.058
< 0.054
< 1.45
124
0.097
0.737
0.015
< 0.036
< 0.320
< 0.163
< 0.032
0.008
< 0.058
< 0.054
< 1.45
80
0.161
0.249
0.01
< 0.036
< 0.320
< 0.163
< 0.032
< 0.005
< 0.058
< 0.054
< 1.45
18
0.052
0.266
0.01
< 0.036
< 0.320
< 0.164
< 0.032
0.021
< 0.059
< 0.054
< 1.45
199
0.097
0.379
0.01
< 0.036
< 0.321
< 0.164
0.078
< 0.005
< 0.059
< 0.054
< 1.45
49
0.108
0.794
0.025
0.045
< 0.320
< 0.164
< 0.032
< 0.005
< 0.059
< 0.054
< 1.45
40
0.073
0.467
0.015
< 0.036
< 0.321
< 0.164
< 0.032
< 0.005
< 0.059
< 0.054
< 1.45
189
< 0.035
0.026
< 0.009
< 0.036
< 0.321
< 0.164
< 0.032
< 0.005
< 0.059
< 0.054
< 1.45
57
0.043
1.71
0.016
0.134
< 0.322
< 0.165
0.168
< 0.005
0.106
0.108
< 1.46
188
< 0.035
0.426
< 0.009
0.061
< 0.322
0.189
< 0.033
< 0.005
0.074
< 0.054
< 1.46
59
0.22
0.735
0.023
0.038
0.394
0.173
0.035
< 0.005
< 0.059
< 0.054
< 1.46
27
< 0.035
0.296
< 0.009
< 0.037
< 0.322
< 0.165
0.044
< 0.005
< 0.059
< 0.054
< 1.46
14
0.361
0.89
0.027
0.037
0.365
0.165
0.083
< 0.005
< 0.059
< 0.054
< 1.46
245
0.17
0.381
< 0.009
0.042
< 0.324
0.182
0.034
< 0.005
0.068
< 0.055
< 1.46
54
0.12
0.888
0.01
0.052
< 0.323
< 0.165
< 0.033
0.009
< 0.059
< 0.055
< 1.46
53
0.073
0.746
0.018
0.054
0.381
< 0.165
0.137
< 0.005
< 0.059
< 0.055
< 1.46
192
0.427
4.87
0.063
0.177
< 0.324
< 0.166
0.357
0.007
0.086
< 0.055
< 1.47
204
< 0.036
0.432
< 0.009
0.064
< 0.325
< 0.166
< 0.033
< 0.005
0.111
< 0.055
< 1.47
219
0.067
0.644
0.011
0.105
< 0.324
0.172
0.106
< 0.005
0.129
< 0.055
< 1.47
141
< 0.036
0.587
< 0.009
< 0.037
< 0.325
0.168
< 0.033
< 0.005
< 0.060
< 0.055
< 1.47
37
0.049
0.305
< 0.009
0.04
< 0.326
< 0.167
< 0.033
< 0.005
< 0.060
< 0.055
< 1.47
181
0.051
0.422
0.016
< 0.037
< 0.326
< 0.167
< 0.033
< 0.005
< 0.060
< 0.055
< 1.48
201
0.054
0.232
0.011
< 0.037
< 0.326
< 0.167
< 0.033
< 0.005
< 0.060
< 0.055
< 1.48
39
< 0.036
0.236
< 0.009
< 0.037
< 0.327
< 0.167
< 0.033
< 0.005
< 0.060
< 0.055
< 1.48
72
0.047
0.881
0.014
0.156
< 0.329
0.173
0.066
0.008
0.169
0.098
< 1.49
128
< 0.036
0.213
< 0.009
< 0.038
< 0.330
< 0.169
< 0.033
< 0.005
0.062
< 0.056
< 1.49
126
0.037
0.62
0.01
0.06
< 0.330
< 0.169
< 0.033
< 0.005
0.091
< 0.056
< 1.49
123
0.115
0.555
< 0.009
< 0.037
< 0.330
< 0.169
< 0.033
0.006
< 0.060
< 0.056
< 1.49
45
0.112
0.202
< 0.009
< 0.037
< 0.329
< 0.168
< 0.033
< 0.005
< 0.060
< 0.056
< 1.49
16
0.189
0.204
0.015
< 0.038
0.52
< 0.170
< 0.034
0.029
< 0.061
< 0.056
< 1.50
243
< 0.036
0.451
< 0.009
0.047
< 0.331
< 0.169
0.037
< 0.005
< 0.061
< 0.056
< 1.50
147
0.1
0.073
< 0.009
< 0.038
< 0.331
< 0.169
< 0.033
< 0.005
< 0.061
< 0.056
< 1.50
148
0.076
0.569
0.019
< 0.038
< 0.331
< 0.169
< 0.034
< 0.005
< 0.061
< 0.056
< 1.50
94
0.082
0.856
< 0.009
0.132
< 0.333
< 0.170
0.136
< 0.005
0.201
0.093
< 1.51
32
< 0.037
0.608
< 0.009
0.052
< 0.334
< 0.171
0.069
< 0.005
0.062
< 0.056
< 1.51
171
0.062
0.799
< 0.009
0.153
< 0.333
< 0.170
0.102
< 0.005
0.198
< 0.056
< 1.51
109
0.446
0.242
0.01
< 0.038
< 0.334
< 0.171
< 0.034
< 0.005
< 0.061
< 0.057
< 1.51
195
< 0.037
0.245
< 0.009
< 0.038
< 0.335
< 0.171
< 0.034
0.009
< 0.061
< 0.057
< 1.52
216
0.04
0.129
< 0.009
< 0.038
< 0.335
< 0.171
< 0.034
< 0.005
< 0.061
< 0.057
< 1.52
108
< 0.037
0.283
0.012
< 0.038
< 0.336
< 0.172
< 0.034
< 0.005
< 0.062
< 0.057
< 1.52
41
0.187
0.993
0.015
0.084
< 0.338
< 0.173
0.094
0.012
0.117
0.099
< 1.53
221
0.208
0.552
0.013
0.045
0.712
< 0.173
< 0.034
0.008
0.07
< 0.057
< 1.53
134
0.065
0.557
0.01
0.05
0.754
< 0.173
0.128
< 0.005
< 0.062
< 0.057
< 1.53
55
0.17
0.584
0.016
0.044
0.496
0.33
0.158
< 0.005
< 0.062
< 0.057
< 1.53
13
0.062
0.336
0.011
< 0.038
< 0.337
< 0.173
< 0.034
< 0.005
< 0.062
< 0.057
< 1.53
65
0.159
0.597
< 0.010
0.079
< 0.341
< 0.175
< 0.035
0.011
0.084
0.058
< 1.54
236
< 0.037
0.004
< 0.010
< 0.039
< 0.340
< 0.174
< 0.034
< 0.006
< 0.062
< 0.057
< 1.54
30
0.133
0.432
0.012
< 0.039
< 0.340
< 0.174
< 0.034
0.007
< 0.062
< 0.058
< 1.54
187
0.163
0.824
< 0.010
0.047
< 0.340
< 0.174
0.05
< 0.006
< 0.062
< 0.058
< 1.54
4
0.142
0.737
0.011
< 0.039
< 0.343
< 0.175
0.062
0.007
< 0.063
< 0.058
< 1.55
26
0.164
1.42
0.024
< 0.039
0.374
< 0.175
0.066
0.01
< 0.063
< 0.058
< 1.55
46
0.362
0.501
0.022
< 0.039
0.431
0.211
< 0.035
0.013
< 0.063
< 0.058
< 1.55
253
0.067
0.252
< 0.010
0.039
< 0.343
< 0.176
< 0.035
< 0.006
< 0.063
< 0.058
< 1.55
66
0.043
0.495
0.011
0.081
< 0.346
< 0.177
< 0.035
0.006
0.167
< 0.059
< 1.57
47
0.199
0.514
< 0.010
0.047
0.564
< 0.178
0.096
< 0.006
< 0.064
< 0.059
< 1.58
159
0.116
0.654
< 0.010
< 0.040
< 0.350
0.179
< 0.035
< 0.006
< 0.064
< 0.059
< 1.58
3
0.136
0.501
0.018
0.042
< 0.350
< 0.179
< 0.035
< 0.006
< 0.064
< 0.059
< 1.58
111
< 0.038
0.484
0.015
< 0.040
0.63
< 0.179
< 0.035
< 0.006
< 0.064
< 0.059
< 1.58
7
< 0.038
0.205
< 0.010
< 0.040
< 0.349
< 0.179
< 0.035
< 0.006
< 0.064
< 0.059
< 1.58
82
< 0.038
0.252
< 0.010
< 0.040
< 0.351
< 0.180
< 0.036
< 0.006
< 0.064
< 0.059
< 1.59
217
0.102
0.416
0.016
< 0.040
0.71
< 0.181
< 0.036
< 0.006
< 0.065
< 0.060
< 1.60
178
< 0.039
0.006
< 0.010
< 0.040
< 0.354
< 0.181
< 0.036
< 0.006
< 0.065
< 0.060
< 1.60
205
0.138
0.365
0.01
< 0.040
< 0.355
< 0.182
< 0.036
< 0.006
< 0.065
< 0.060
< 1.61
146
0.117
0.136
< 0.010
0.08
< 0.368
< 0.188
< 0.037
< 0.006
0.083
< 0.062
< 1.66
90
< 0.041
0.331
0.014
< 0.043
0.588
< 0.192
< 0.038
< 0.006
< 0.069
< 0.064
< 1.70
164
< 0.042
0.161
< 0.011
0.073
< 0.379
< 0.194
< 0.038
< 0.006
0.078
< 0.064
< 1.72
96
< 0.046
0.385
< 0.012
0.075
0.909
< 0.217
0.124
< 0.007
< 0.078
< 0.072
< 1.92
92
< 0.047
0.192
< 0.012
< 0.049
< 0.431
< 0.220
< 0.044
< 0.007
< 0.079
< 0.073
< 1.95
1
0.213
0.752
0.028
< 0.058
< 0.510
< 0.261
0.053
< 0.008
< 0.093
< 0.086
< 2.31
PFHxS2
PFOS1
PFHpS
PFUnA
PFOA
PFNA
PFDA1
PFPeS
PFTriA
PFTA
PFHxA
%> LOD
74.6
99.2
54.9
49.2
27.0
21.3
39.3
31.1
29.5
6.6
1.6
Maximum
0.446
4.87
0.063
0.240
1.23
0.494
0.465
0.035
0.336
0.111
5.87
Minimum
< 0.033
< 0.001
< 0.008
< 0.033
< 0.290
< 0.148
< 0.030
< 0.005
< 0.050
< 0.049
< 1.32
Median
0.067
0.4795
0.009
< 0.031
< 0.315
< 0.163
< 0.031
< 0.005
< 0.057
< 0.054
< 1.45
PFPeS PFHxS PFHpS PFOS PFHxA PFOA PFNA PFDA PFUnA PFTriA PFTA Chain length 5 6 7 8 6 8 9 10 11 13 14
%> LOD 31.1 74.6 54.9 99.2 1.6 27.0 21.3 39.3 49.2 29.5 6.6 Maximum 0.035 0.446 0.063 4.87 5.87 1.23 0.494 0.465 0.24 0.336 0.111 Minimum < 0.005 < 0.033 < 0.008 < 0.001 < 1.32 < 0.290 < 0.148 < 0.030 < 0.033 < 0.050 < 0.049 Median < 0.005 0.067 0.009 0.48 < 1.45 < 0.315 < 0.163 < 0.031 < 0.031 < 0.057 < 0.054
n 122 122 122 122 122 122 122 122 122 122 122
What are the levels of PFAS in the placenta?
PFAS results are presented as ng/g wet weight
• 122 placentas from high-risk pregnancies at UNC Hospitals • Pre-Term Birth cohort • Monitored for a total of 26 PFAS • Including GenX, Nafion BP2 previously seen in Wilmington serum • 11 legacy PFAS found above limit of detection (LOD)
n = 34n = 78
PFAS Sample ID
PFAS Sample ID
Cannot report: interfering peaks or contaminantion in Mass Spec line
PFBA
PFHpA
Extra
Risk factors associated with elevated PFAS in PTB placenta
PFOS, PFHxS, PFHps, and PFUnA were investigated for associations with risk factors including: • Maternal age
• Maternal smoking status
• Maternal education
• Marital status
• PFOS, PFHxS, PFHps, and PFUnA were investigated for associations with risk factors including: • Maternal age
• Maternal smoking status
p = 0.0283 p = 0.0002
PFOS, PFHxS, PFHps, and PFUnA in relation to adverse outcomes:
• Preeclampsia
• Birthweight
PFAS and adverse outcomes
18 20 22 24 26 28 30 32 34 36 38 40
Gestational Age at Delivery (weeks)
0.00
0.04
0.08
0.12
0.56
0.60
PFAS and adverse outcomes
18 20 22 24 26 28 30 32 34 36 38 40
Gestational Age at Delivery (weeks)
0.00
0.04
0.08
0.12
0.56
0.60
No significant associations were observed between PFAS and any investigated adverse outcome for this study
Examining the effects of PFAS in cell culture
• Late in the first trimester, cells of the placenta known as trophoblast cells migrate to invade and remodel the arteries of the uterine wall.
• Remodeling allows for increased blood flow to the placenta and growing fetus.
• When this migration and invasion of trophoblast is compromised, pregnancy complications develop like Preeclampsia.
PFAS reduce migration in SVneo/HTR8
40 60 80 0
50
100
N = mean of 3 experiments * p < .05 compared to control
Time
https://www.rndsystems.com/resources/articles/chemokines-pregnancy
• Protects fetus against pathogens
Chemokine expression
N = mean of 4 experiments * p < .05 compared to control
CTR
PFAS induced changes in migration
OUR TEAM: UNC at Chapel Hill
Dr. Rebecca Fry
Dr. John Szilagyi
Dr. Jackie Bangma
Dr. Martha Scott
Discussion Questions
• Who needs to know about this research? • How can these results inform clinical practice? • Can we use these data to drive in vivo work?
PFAS and placental toxicity
Slide Number 8
Slide Number 9
PFAS reduce migration in SVneo/HTR8
Immune regulation of trophoblast migration
Chemokine expression
Big picture
Extra slides