Prenatal Metal Exposure Alters the Placental Proteome in a Sex-Dependent Manner in Extremely Low Gestational Age Newborns: Links to Gestational Age
Abstract
:1. Introduction
2. Results
2.1. Demographic Characteristics of Study Participants
2.2. Trace Elements in Umbilical Cord Tissue
2.3. The Identification of Metal-Associated Proteins
2.4. Biological Functional Analysis of the MAPs
2.5. Upstream Regulator Analysis of the MAPs
2.6. Associations of MAPs with Placental Weight and Gestational Age
3. Discussion
4. Materials and Methods
4.1. The ELGAN Cohort
4.2. Placental Tissue Collection and Quantification of Protein Expression
4.3. Umbilical Cord Tissue Collection and Trace Element Measurements
4.4. Covariate Selection
4.5. Significance Tests across Demographic Characteristics
4.6. Evaluation of the Relationship between Trace Elements and Placental Protein Expression
4.7. Assessment of MAP Associations with Pregnancy or Neonatal Outcomes
4.8. Network Interaction Analysis
4.9. Biological Functional Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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All Participants (n = 230) | Females (n = 99) | Males (n = 131) | p-Value | |
---|---|---|---|---|
Maternal age (average) | 29.6 [6.70] | 28.9 [6.59] | 30.1 [6.75] | 0.159 |
Gestational age in weeks (average) | 26.0 [1.26] | 26.1 [1.22] | 25.9 [1.28] | 0.230 |
Birthweight in grams | 825 [183] | 810 [188] | 839 [179] | 0.282 |
Birthweight z-score | −0.22 [1.03] | −0.37 [1.15] | −0.10 [0.91] | 0.057 |
Placental weight in grams | 246 [121] | 260 [122] | 236 [119] | 0.139 |
C-section delivery | ||||
Yes | 162 (70.4%) | 70 (70.7%) | 92 (70.2%) | 1.000 |
No | 68 (29.6%) | 29 (29.3%) | 39 (29.8%) | |
Duration of labor | ||||
0 h | 64 (27.8%) | 28 (28.3%) | 36 (27.5%) | 0.851 |
≤12 h | 50 (21.7%) | 23 (23.2%) | 27 (20.6%) | |
>12 h | 116 (50.4%) | 48 (48.5%) | 68 (51.9%) | |
Public insurance | ||||
No | 150 (65.2%) | 60 (60.6%) | 90 (68.7%) | 0.262 |
Yes | 78 (33.9%) | 38 (38.4%) | 40 (30.5%) | |
“Missing” | 2 (0.87%) | 1 (1.01%) | 1 (0.76%) | |
Mother’s education (years) | ||||
≤12 | 93 (40.9%) | 42 (42.4%) | 51 (38.9%) | 0.260 |
3–15 | 49 (21.3%) | 24 (24.2%) | 25 (19.1%) | |
16+ | 84 (36.5%) | 30 (30.3%) | 54 (41.2%) | |
“Missing” | 4 (1.74%) | 3 (3.03%) | 1 (0.76%) | |
Mother’s race | ||||
White | 136 (59.1%) | 57 (57.6%) | 79 (60.3%) | 0.684 |
Black | 70 (30.4%) | 33 (33.3%) | 37 (28.2%) | |
Other | 21 (9.13%) | 8 (8.08%) | 13 (9.92%) | |
“Missing” | 3 (1.30%) | 1 (1.01%) | 2 (1.53%) | |
Marital status (married) | ||||
No | 104 (45.2%) | 49 (49.5%) | 55 (42.0%) | 0.318 |
Yes | 126 (54.8%) | 50 (50.5%) | 76 (58.0%) | |
Maternal pre-pregnancy BMI | ||||
Underweight | 18 (7.83%) | 6 (6.06%) | 12 (9.16%) | 0.573 |
Normal | 115 (50.0%) | 46 (46.5%) | 69 (52.7%) | |
Overweight | 39 (17.0%) | 19 (19.2%) | 20 (15.3%) | |
Obese | 53 (23.0%) | 25 (25.3%) | 28 (21.4%) | |
“Missing” | 5 (2.17%) | 3 (3.03%) | 2 (1.53%) | |
Maternal smoking while pregnant | ||||
No | 204 (88.7%) | 86 (86.9%) | 118 (90.1%) | 0.765 |
Yes | 23 (10.0%) | 11 (11.1%) | 12 (9.16%) | |
“Missing” | 3 (1.30%) | 2 (2.02%) | 1 (0.76%) | |
Maternal SES score | ||||
0 | 109 (47.4%) | 43 (43.4%) | 66 (50.4%) | 0.149 |
1 | 36 (15.7%) | 13 (13.1%) | 23 (17.6%) | |
2 | 55 (23.9%) | 26 (26.3%) | 29 (22.1%) | |
3 | 23 (10.0%) | 15 (15.2%) | 8 (6.11%) | |
4 | 7 (3.04%) | 2 (2.02%) | 5 (3.82%) |
Metal | Sex | Median | Mean | Minimum | Maximum | p-Value |
---|---|---|---|---|---|---|
Selenium (Se) | Female | 0.880 | 0.877 | 0.436 | 1.610 | 0.493 |
Male | 0.851 | 0.892 | 0.600 | 1.980 | ||
Manganese (Mn) | Female | 0.342 | 0.432 | 0.101 | 5.577 | 0.310 |
Male | 0.344 | 0.373 | 0.194 | 1.699 | ||
Lead (Pb) | Female | 0.014 | 0.029 | 0.003 | 0.350 | 0.463 |
Male | 0.017 | 0.036 | 0.003 | 0.893 | ||
Arsenic (As) | Female | 0.004 | 0.006 | 0.001 | 0.078 | 0.600 |
Male | 0.005 | 0.007 | 0.001 | 0.067 | ||
Cadmium (Cd) | Female | 0.001 | 0.005 | 0.0002 | 0.075 | 0.204 |
Male | 0.001 | 0.045 | 0.0002 | 4.06 |
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Freedman, A.N.; Roell, K.; Engwall, E.; Bulka, C.; Kuban, K.C.K.; Herring, L.; Mills, C.A.; Parsons, P.J.; Galusha, A.; O’Shea, T.M.; et al. Prenatal Metal Exposure Alters the Placental Proteome in a Sex-Dependent Manner in Extremely Low Gestational Age Newborns: Links to Gestational Age. Int. J. Mol. Sci. 2023, 24, 14977. https://doi.org/10.3390/ijms241914977
Freedman AN, Roell K, Engwall E, Bulka C, Kuban KCK, Herring L, Mills CA, Parsons PJ, Galusha A, O’Shea TM, et al. Prenatal Metal Exposure Alters the Placental Proteome in a Sex-Dependent Manner in Extremely Low Gestational Age Newborns: Links to Gestational Age. International Journal of Molecular Sciences. 2023; 24(19):14977. https://doi.org/10.3390/ijms241914977
Chicago/Turabian StyleFreedman, Anastasia N., Kyle Roell, Eiona Engwall, Catherine Bulka, Karl C. K. Kuban, Laura Herring, Christina A. Mills, Patrick J. Parsons, Aubrey Galusha, Thomas Michael O’Shea, and et al. 2023. "Prenatal Metal Exposure Alters the Placental Proteome in a Sex-Dependent Manner in Extremely Low Gestational Age Newborns: Links to Gestational Age" International Journal of Molecular Sciences 24, no. 19: 14977. https://doi.org/10.3390/ijms241914977
APA StyleFreedman, A. N., Roell, K., Engwall, E., Bulka, C., Kuban, K. C. K., Herring, L., Mills, C. A., Parsons, P. J., Galusha, A., O’Shea, T. M., & Fry, R. C. (2023). Prenatal Metal Exposure Alters the Placental Proteome in a Sex-Dependent Manner in Extremely Low Gestational Age Newborns: Links to Gestational Age. International Journal of Molecular Sciences, 24(19), 14977. https://doi.org/10.3390/ijms241914977