Prenatal Metal Exposure Alters the Placental Proteome in a Sex-Dependent Manner in Extremely Low Gestational Age Newborns: Links to Gestational Age Article Swipe

PDF

Freedman A.N. , Kyle R. Roell , Eiona Engwall , Catherine M. Bulka , Kuban K.C.K. , Laura E. Herring , Mills C.A. , Pandya Shashank J , Aubrey L. Galusha , O’Shea T.M. , Fry R.C. ·

YOU? · · 2023 · Open Access · · DOI: https://doi.org/10.17615/10wc-6648

Prenatal exposure to toxic metals is associated with altered placental function and adverse infant and child health outcomes. Adverse outcomes include those that are observed at the time of birth, such as low birthweight, as well as those that arise later in life, such as neurological impairment. It is often the case that these adverse outcomes show sex-specific responses in relation to toxicant exposures. While the precise molecular mechanisms linking in utero toxic metal exposures with later-in-life health are unknown, placental inflammation is posited to play a critical role. Here, we sought to understand whether in utero metal exposure is associated with alterations in the expression of the placental proteome by identifying metal associated proteins (MAPs). Within the Extremely Low Gestational Age Newborns (ELGAN) cohort (n = 230), placental and umbilical cord tissue samples were collected at birth. Arsenic (As), cadmium (Cd), lead (Pb), selenium (Se), and manganese (Mn) concentrations were measured in umbilical cord tissue samples via ICP-MS/MS. Protein expression was examined in placental samples using an LC-MS/MS-based, global, untargeted proteomics analysis measuring more than 3400 proteins. MAPs were then evaluated for associations with pregnancy and neonatal outcomes, including placental weight and gestational age. We hypothesized that metal levels would be positively associated with the altered expression of inflammation/immune-associated pathways and that sex-specific patterns of metal-associated placental protein expression would be observed. Sex-specific analyses identified 89 unique MAPs expressed in female placentas and 41 unique MAPs expressed in male placentas. Notably, many of the female-associated MAPs are known to be involved in immune-related processes, while the male-associated MAPs are associated with intracellular transport and cell localization. Further, several MAPs were significantly associated with gestational age in males and females and placental weight in males. These data highlight the linkage between prenatal metal exposure and an altered placental proteome, with implications for altering the trajectory of fetal development.

Related Topics

Concepts

Obstetrics Gestational age Gestation Fetus Medicine Proteome Pregnancy Biology Bioinformatics Genetics

Metadata

Type: article
Language: en
Landing Page: https://doi.org/10.17615/10wc-6648
PDF: https://doi.org/10.17615/10wc-6648
OA Status: gold
Related Works: 10
OpenAlex ID: https://openalex.org/W4388443757

All OpenAlex metadata

Raw OpenAlex JSON

OpenAlex ID: https://openalex.org/W4388443757

Canonical identifier for this work in OpenAlex
DOI: https://doi.org/10.17615/10wc-6648

Digital Object Identifier
Title: Prenatal Metal Exposure Alters the Placental Proteome in a Sex-Dependent Manner in Extremely Low Gestational Age Newborns: Links to Gestational Age

Work title
Type: article

OpenAlex work type
Language: en

Primary language
Publication year: 2023

Year of publication
Publication date: 2023-01-01

Full publication date if available
Authors: Freedman A.N., Kyle R. Roell, Eiona Engwall, Catherine M. Bulka, Kuban K.C.K., Laura E. Herring, Mills C.A., Pandya Shashank J, Aubrey L. Galusha, O’Shea T.M., Fry R.C.

List of authors in order
Landing page: https://doi.org/10.17615/10wc-6648

Publisher landing page
PDF URL: https://doi.org/10.17615/10wc-6648

Direct link to full text PDF
Open access: Yes

Whether a free full text is available
OA status: gold

Open access status per OpenAlex
OA URL: https://doi.org/10.17615/10wc-6648

Direct OA link when available
Concepts: Obstetrics, Gestational age, Gestation, Fetus, Medicine, Proteome, Pregnancy, Biology, Bioinformatics, Genetics

Top concepts (fields/topics) attached by OpenAlex
Cited by: 0

Total citation count in OpenAlex
Related works (count): 10

Other works algorithmically related by OpenAlex

Full payload

id	https://openalex.org/W4388443757
doi	https://doi.org/10.17615/10wc-6648
ids.openalex	https://openalex.org/W4388443757
fwci	0.0
type	article
title	Prenatal Metal Exposure Alters the Placental Proteome in a Sex-Dependent Manner in Extremely Low Gestational Age Newborns: Links to Gestational Age
biblio.issue
biblio.volume
biblio.last_page
biblio.first_page
topics[0].id	https://openalex.org/T10790
topics[0].field.id	https://openalex.org/fields/23
topics[0].field.display_name	Environmental Science
topics[0].score	0.9488000273704529
topics[0].domain.id	https://openalex.org/domains/3
topics[0].domain.display_name	Physical Sciences
topics[0].subfield.id	https://openalex.org/subfields/2307
topics[0].subfield.display_name	Health, Toxicology and Mutagenesis
topics[0].display_name	Heavy Metal Exposure and Toxicity
topics[1].id	https://openalex.org/T10686
topics[1].field.id	https://openalex.org/fields/23
topics[1].field.display_name	Environmental Science
topics[1].score	0.9473999738693237
topics[1].domain.id	https://openalex.org/domains/3
topics[1].domain.display_name	Physical Sciences
topics[1].subfield.id	https://openalex.org/subfields/2307
topics[1].subfield.display_name	Health, Toxicology and Mutagenesis
topics[1].display_name	Effects and risks of endocrine disrupting chemicals
is_xpac	False
apc_list
apc_paid
concepts[0].id	https://openalex.org/C131872663
concepts[0].level	1
concepts[0].score	0.6337616443634033
concepts[0].wikidata	https://www.wikidata.org/wiki/Q5284418
concepts[0].display_name	Obstetrics
concepts[1].id	https://openalex.org/C2778376644
concepts[1].level	3
concepts[1].score	0.6104928851127625
concepts[1].wikidata	https://www.wikidata.org/wiki/Q2253111
concepts[1].display_name	Gestational age
concepts[2].id	https://openalex.org/C46973012
concepts[2].level	3
concepts[2].score	0.5765442848205566
concepts[2].wikidata	https://www.wikidata.org/wiki/Q28627
concepts[2].display_name	Gestation
concepts[3].id	https://openalex.org/C172680121
concepts[3].level	3
concepts[3].score	0.5110167264938354
concepts[3].wikidata	https://www.wikidata.org/wiki/Q26513
concepts[3].display_name	Fetus
concepts[4].id	https://openalex.org/C71924100
concepts[4].level	0
concepts[4].score	0.47442692518234253
concepts[4].wikidata	https://www.wikidata.org/wiki/Q11190
concepts[4].display_name	Medicine
concepts[5].id	https://openalex.org/C104397665
concepts[5].level	2
concepts[5].score	0.4107200503349304
concepts[5].wikidata	https://www.wikidata.org/wiki/Q860947
concepts[5].display_name	Proteome
concepts[6].id	https://openalex.org/C2779234561
concepts[6].level	2
concepts[6].score	0.3809775710105896
concepts[6].wikidata	https://www.wikidata.org/wiki/Q11995
concepts[6].display_name	Pregnancy
concepts[7].id	https://openalex.org/C86803240
concepts[7].level	0
concepts[7].score	0.22764045000076294
concepts[7].wikidata	https://www.wikidata.org/wiki/Q420
concepts[7].display_name	Biology
concepts[8].id	https://openalex.org/C60644358
concepts[8].level	1
concepts[8].score	0.15995067358016968
concepts[8].wikidata	https://www.wikidata.org/wiki/Q128570
concepts[8].display_name	Bioinformatics
concepts[9].id	https://openalex.org/C54355233
concepts[9].level	1
concepts[9].score	0.06206902861595154
concepts[9].wikidata	https://www.wikidata.org/wiki/Q7162
concepts[9].display_name	Genetics
keywords[0].id	https://openalex.org/keywords/obstetrics
keywords[0].score	0.6337616443634033
keywords[0].display_name	Obstetrics
keywords[1].id	https://openalex.org/keywords/gestational-age
keywords[1].score	0.6104928851127625
keywords[1].display_name	Gestational age
keywords[2].id	https://openalex.org/keywords/gestation
keywords[2].score	0.5765442848205566
keywords[2].display_name	Gestation
keywords[3].id	https://openalex.org/keywords/fetus
keywords[3].score	0.5110167264938354
keywords[3].display_name	Fetus
keywords[4].id	https://openalex.org/keywords/medicine
keywords[4].score	0.47442692518234253
keywords[4].display_name	Medicine
keywords[5].id	https://openalex.org/keywords/proteome
keywords[5].score	0.4107200503349304
keywords[5].display_name	Proteome
keywords[6].id	https://openalex.org/keywords/pregnancy
keywords[6].score	0.3809775710105896
keywords[6].display_name	Pregnancy
keywords[7].id	https://openalex.org/keywords/biology
keywords[7].score	0.22764045000076294
keywords[7].display_name	Biology
keywords[8].id	https://openalex.org/keywords/bioinformatics
keywords[8].score	0.15995067358016968
keywords[8].display_name	Bioinformatics
keywords[9].id	https://openalex.org/keywords/genetics
keywords[9].score	0.06206902861595154
keywords[9].display_name	Genetics
language	en
locations[0].id	pmh:cdr.lib.unc.edu:000009367
locations[0].is_oa	True
locations[0].source
locations[0].license
locations[0].pdf_url	https://doi.org/10.17615/10wc-6648
locations[0].version	submittedVersion
locations[0].raw_type	Article
locations[0].license_id
locations[0].is_accepted	False
locations[0].is_published	False
locations[0].raw_source_name	International Journal of Molecular Sciences, 24(19)
locations[0].landing_page_url	https://doi.org/10.17615/10wc-6648
authorships[0].author.id	https://openalex.org/A5093210721
authorships[0].author.orcid
authorships[0].author.display_name	Freedman A.N.
authorships[0].author_position	first
authorships[0].raw_author_name	Freedman A.N.
authorships[0].is_corresponding	False
authorships[1].author.id	https://openalex.org/A5008906493
authorships[1].author.orcid	https://orcid.org/0000-0001-7491-6095
authorships[1].author.display_name	Kyle R. Roell
authorships[1].author_position	middle
authorships[1].raw_author_name	Roell K.
authorships[1].is_corresponding	False
authorships[2].author.id	https://openalex.org/A5093021086
authorships[2].author.orcid	https://orcid.org/0009-0002-2092-6495
authorships[2].author.display_name	Eiona Engwall
authorships[2].author_position	middle
authorships[2].raw_author_name	Engwall E.
authorships[2].is_corresponding	False
authorships[3].author.id	https://openalex.org/A5017617910
authorships[3].author.orcid	https://orcid.org/0000-0002-6529-7226
authorships[3].author.display_name	Catherine M. Bulka
authorships[3].author_position	middle
authorships[3].raw_author_name	Bulka C.
authorships[3].is_corresponding	False
authorships[4].author.id	https://openalex.org/A5093210724
authorships[4].author.orcid
authorships[4].author.display_name	Kuban K.C.K.
authorships[4].author_position	middle
authorships[4].raw_author_name	Kuban K.C.K.
authorships[4].is_corresponding	False
authorships[5].author.id	https://openalex.org/A5053713564
authorships[5].author.orcid	https://orcid.org/0000-0003-4496-7312
authorships[5].author.display_name	Laura E. Herring
authorships[5].author_position	middle
authorships[5].raw_author_name	Herring L.
authorships[5].is_corresponding	False
authorships[6].author.id	https://openalex.org/A5111070230
authorships[6].author.orcid
authorships[6].author.display_name	Mills C.A.
authorships[6].author_position	middle
authorships[6].raw_author_name	Mills C.A.
authorships[6].is_corresponding	False
authorships[7].author.id	https://openalex.org/A5111070231
authorships[7].author.orcid
authorships[7].author.display_name	Pandya Shashank J
authorships[7].author_position	middle
authorships[7].raw_author_name	Parsons P.J.
authorships[7].is_corresponding	False
authorships[8].author.id	https://openalex.org/A5009672713
authorships[8].author.orcid	https://orcid.org/0000-0001-8351-0396
authorships[8].author.display_name	Aubrey L. Galusha
authorships[8].author_position	middle
authorships[8].raw_author_name	Galusha A.
authorships[8].is_corresponding	False
authorships[9].author.id	https://openalex.org/A5093210722
authorships[9].author.orcid
authorships[9].author.display_name	O’Shea T.M.
authorships[9].author_position	middle
authorships[9].raw_author_name	O’Shea T.M.
authorships[9].is_corresponding	False
authorships[10].author.id	https://openalex.org/A5093210723
authorships[10].author.orcid
authorships[10].author.display_name	Fry R.C.
authorships[10].author_position	last
authorships[10].raw_author_name	Fry R.C.
authorships[10].is_corresponding	False
has_content.pdf	True
has_content.grobid_xml	False
is_paratext	False
open_access.is_oa	True
open_access.oa_url	https://doi.org/10.17615/10wc-6648
open_access.oa_status	gold
open_access.any_repository_has_fulltext	False
created_date	2023-11-07T00:00:00
display_name	Prenatal Metal Exposure Alters the Placental Proteome in a Sex-Dependent Manner in Extremely Low Gestational Age Newborns: Links to Gestational Age
has_fulltext	False
is_retracted	False
updated_date	2025-11-06T03:46:38.306776
primary_topic.id	https://openalex.org/T10790
primary_topic.field.id	https://openalex.org/fields/23
primary_topic.field.display_name	Environmental Science
primary_topic.score	0.9488000273704529
primary_topic.domain.id	https://openalex.org/domains/3
primary_topic.domain.display_name	Physical Sciences
primary_topic.subfield.id	https://openalex.org/subfields/2307
primary_topic.subfield.display_name	Health, Toxicology and Mutagenesis
primary_topic.display_name	Heavy Metal Exposure and Toxicity
related_works	https://openalex.org/W2041269450, https://openalex.org/W2397830406, https://openalex.org/W1996912214, https://openalex.org/W2046375634, https://openalex.org/W2107304850, https://openalex.org/W2034531855, https://openalex.org/W2004317605, https://openalex.org/W2063828562, https://openalex.org/W2017292534, https://openalex.org/W2411232222
cited_by_count	0
locations_count	1
best_oa_location.id	pmh:cdr.lib.unc.edu:000009367
best_oa_location.is_oa	True
best_oa_location.source
best_oa_location.license
best_oa_location.pdf_url	https://doi.org/10.17615/10wc-6648
best_oa_location.version	submittedVersion
best_oa_location.raw_type	Article
best_oa_location.license_id
best_oa_location.is_accepted	False
best_oa_location.is_published	False
best_oa_location.raw_source_name	International Journal of Molecular Sciences, 24(19)
best_oa_location.landing_page_url	https://doi.org/10.17615/10wc-6648
primary_location.id	pmh:cdr.lib.unc.edu:000009367
primary_location.is_oa	True
primary_location.source
primary_location.license
primary_location.pdf_url	https://doi.org/10.17615/10wc-6648
primary_location.version	submittedVersion
primary_location.raw_type	Article
primary_location.license_id
primary_location.is_accepted	False
primary_location.is_published	False
primary_location.raw_source_name	International Journal of Molecular Sciences, 24(19)
primary_location.landing_page_url	https://doi.org/10.17615/10wc-6648
publication_date	2023-01-01
publication_year	2023
referenced_works_count	0
abstract_inverted_index.=	126
abstract_inverted_index.a	86
abstract_inverted_index.(n	125
abstract_inverted_index.41	234
abstract_inverted_index.89	226
abstract_inverted_index.It	47
abstract_inverted_index.We	195
abstract_inverted_index.an	167, 295
abstract_inverted_index.as	31, 34, 36, 44
abstract_inverted_index.at	25, 136
abstract_inverted_index.be	201, 221, 250
abstract_inverted_index.by	110
abstract_inverted_index.in	41, 59, 70, 95, 103, 152, 163, 230, 238, 252, 276, 283
abstract_inverted_index.is	5, 48, 82, 99
abstract_inverted_index.of	28, 106, 208, 215, 243, 305
abstract_inverted_index.to	2, 61, 84, 92, 249
abstract_inverted_index.we	90
abstract_inverted_index.Age	121
abstract_inverted_index.Low	119
abstract_inverted_index.age	275
abstract_inverted_index.and	11, 14, 129, 146, 186, 192, 211, 233, 264, 278, 280, 294
abstract_inverted_index.are	23, 78, 247, 259
abstract_inverted_index.for	182, 301
abstract_inverted_index.low	32
abstract_inverted_index.the	26, 50, 65, 104, 107, 117, 205, 244, 256, 288, 303
abstract_inverted_index.via	157
abstract_inverted_index.was	161
abstract_inverted_index.(Mn)	148
abstract_inverted_index.3400	176
abstract_inverted_index.MAPs	178, 228, 236, 246, 258, 269
abstract_inverted_index.age.	194
abstract_inverted_index.case	51
abstract_inverted_index.cell	265
abstract_inverted_index.cord	131, 154
abstract_inverted_index.data	286
abstract_inverted_index.lead	142
abstract_inverted_index.male	239
abstract_inverted_index.many	242
abstract_inverted_index.more	174
abstract_inverted_index.play	85
abstract_inverted_index.show	56
abstract_inverted_index.such	30, 43
abstract_inverted_index.than	175
abstract_inverted_index.that	22, 38, 52, 197, 212
abstract_inverted_index.then	180
abstract_inverted_index.time	27
abstract_inverted_index.well	35
abstract_inverted_index.were	134, 150, 179, 270
abstract_inverted_index.with	7, 75, 101, 184, 204, 261, 273, 299
abstract_inverted_index.(As),	139
abstract_inverted_index.(Cd),	141
abstract_inverted_index.(Pb),	143
abstract_inverted_index.(Se),	145
abstract_inverted_index.230),	127
abstract_inverted_index.Here,	89
abstract_inverted_index.These	285
abstract_inverted_index.While	64
abstract_inverted_index.arise	39
abstract_inverted_index.child	15
abstract_inverted_index.fetal	306
abstract_inverted_index.known	248
abstract_inverted_index.later	40
abstract_inverted_index.life,	42
abstract_inverted_index.males	277
abstract_inverted_index.metal	73, 97, 112, 198, 292
abstract_inverted_index.often	49
abstract_inverted_index.role.	88
abstract_inverted_index.these	53
abstract_inverted_index.those	21, 37
abstract_inverted_index.toxic	3, 72
abstract_inverted_index.using	166
abstract_inverted_index.utero	71, 96
abstract_inverted_index.while	255
abstract_inverted_index.would	200, 220
abstract_inverted_index.Within	116
abstract_inverted_index.birth,	29
abstract_inverted_index.birth.	137
abstract_inverted_index.cohort	124
abstract_inverted_index.female	231
abstract_inverted_index.health	16, 77
abstract_inverted_index.infant	13
abstract_inverted_index.levels	199
abstract_inverted_index.males.	284
abstract_inverted_index.metals	4
abstract_inverted_index.sought	91
abstract_inverted_index.tissue	132, 155
abstract_inverted_index.unique	227, 235
abstract_inverted_index.weight	191, 282
abstract_inverted_index.(ELGAN)	123
abstract_inverted_index.(MAPs).	115
abstract_inverted_index.Adverse	18
abstract_inverted_index.Arsenic	138
abstract_inverted_index.Protein	159
abstract_inverted_index.adverse	12, 54
abstract_inverted_index.altered	8, 206, 296
abstract_inverted_index.between	290
abstract_inverted_index.cadmium	140
abstract_inverted_index.females	279
abstract_inverted_index.global,	169
abstract_inverted_index.include	20
abstract_inverted_index.linkage	289
abstract_inverted_index.linking	69
abstract_inverted_index.posited	83
abstract_inverted_index.precise	66
abstract_inverted_index.protein	218
abstract_inverted_index.samples	133, 156, 165
abstract_inverted_index.several	268
abstract_inverted_index.whether	94
abstract_inverted_index.Further,	267
abstract_inverted_index.Newborns	122
abstract_inverted_index.Notably,	241
abstract_inverted_index.Prenatal	0
abstract_inverted_index.altering	302
abstract_inverted_index.analyses	224
abstract_inverted_index.analysis	172
abstract_inverted_index.critical	87
abstract_inverted_index.examined	162
abstract_inverted_index.exposure	1, 98, 293
abstract_inverted_index.function	10
abstract_inverted_index.involved	251
abstract_inverted_index.measured	151
abstract_inverted_index.neonatal	187
abstract_inverted_index.observed	24
abstract_inverted_index.outcomes	19, 55
abstract_inverted_index.pathways	210
abstract_inverted_index.patterns	214
abstract_inverted_index.prenatal	291
abstract_inverted_index.proteins	114
abstract_inverted_index.proteome	109
abstract_inverted_index.relation	60
abstract_inverted_index.selenium	144
abstract_inverted_index.toxicant	62
abstract_inverted_index.unknown,	79
abstract_inverted_index.Extremely	118
abstract_inverted_index.collected	135
abstract_inverted_index.evaluated	181
abstract_inverted_index.exposures	74
abstract_inverted_index.expressed	229, 237
abstract_inverted_index.highlight	287
abstract_inverted_index.including	189
abstract_inverted_index.manganese	147
abstract_inverted_index.measuring	173
abstract_inverted_index.molecular	67
abstract_inverted_index.observed.	222
abstract_inverted_index.outcomes,	188
abstract_inverted_index.outcomes.	17
abstract_inverted_index.placental	9, 80, 108, 128, 164, 190, 217, 281, 297
abstract_inverted_index.placentas	232
abstract_inverted_index.pregnancy	185
abstract_inverted_index.proteins.	177
abstract_inverted_index.proteome,	298
abstract_inverted_index.responses	58
abstract_inverted_index.transport	263
abstract_inverted_index.umbilical	130, 153
abstract_inverted_index.ICP-MS/MS.	158
abstract_inverted_index.associated	6, 100, 113, 203, 260, 272
abstract_inverted_index.exposures.	63
abstract_inverted_index.expression	105, 160, 207, 219
abstract_inverted_index.identified	225
abstract_inverted_index.mechanisms	68
abstract_inverted_index.placentas.	240
abstract_inverted_index.positively	202
abstract_inverted_index.processes,	254
abstract_inverted_index.proteomics	171
abstract_inverted_index.trajectory	304
abstract_inverted_index.understand	93
abstract_inverted_index.untargeted	170
abstract_inverted_index.Gestational	120
abstract_inverted_index.alterations	102
abstract_inverted_index.gestational	193, 274
abstract_inverted_index.identifying	111
abstract_inverted_index.impairment.	46
abstract_inverted_index.Sex-specific	223
abstract_inverted_index.associations	183
abstract_inverted_index.birthweight,	33
abstract_inverted_index.development.	307
abstract_inverted_index.hypothesized	196
abstract_inverted_index.implications	300
abstract_inverted_index.inflammation	81
abstract_inverted_index.neurological	45
abstract_inverted_index.sex-specific	57, 213
abstract_inverted_index.intracellular	262
abstract_inverted_index.later-in-life	76
abstract_inverted_index.localization.	266
abstract_inverted_index.significantly	271
abstract_inverted_index.concentrations	149
abstract_inverted_index.immune-related	253
abstract_inverted_index.LC-MS/MS-based,	168
abstract_inverted_index.male-associated	257
abstract_inverted_index.metal-associated	216
abstract_inverted_index.female-associated	245
abstract_inverted_index.inflammation/immune-associated	209
cited_by_percentile_year
countries_distinct_count	0
institutions_distinct_count	11
citation_normalized_percentile.value	0.21742683
citation_normalized_percentile.is_in_top_1_percent	False
citation_normalized_percentile.is_in_top_10_percent	False