Mapping Steroidogenic Perturbations Under Endocrine Disruptor Mixtures Across Demographic Subgroups: Structural and Metabolomic Insights
Source abstract
Abstract
ABSTRACT Endocrine‐disrupting chemicals (EDCs) are pervasive environmental chemicals affecting hormone homeostasis, yet mapping mixture exposures to mechanisms at the population scale remains challenging. Here, analyses of 4255 U.S. participants are integrated with computational and experimental validation, linking population signals to molecular targets. Profiling 37 EDCs reveals consistent associations between phthalate metabolites and lower testosterone, strongest in adult males. Mono‐(3‐carboxypropyl) phthalate (MCPP) is identified as a key disruptor and is shown to inhibit CYP17A1, consistent with engagement of the enzyme's iron–protoporphyrin IX (heme) center. Docking/molecular dynamics prioritizes this interaction, which is supported by surface plasmon resonance, multi‐matrix metabolomics in vivo and in vitro, and functional assays in primary Leydig cells. An interactive web resource ( https://chembio.njmu.edu.cn/edc‐hormone‐explorer.html ) provides open access to the association landscape and supports risk prioritization.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Effects and risks of endocrine disrupting chemicals · Pharmacological Effects and Toxicity Studies · Folate and B Vitamins Research
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
State Key Laboratory of Reproductive Medicine and Offspring Health Center For Global Health School of Public Health Nanjing Medical University Nanjing China
Key Laboratory of Modern Toxicology of Ministry of Education Nanjing Medical University Nanjing China
Department of Hygienic Analysis and Detection School of Public Health Nanjing Medical University Nanjing China
Department of Epidemiology Center For Global Health School of Public Health Nanjing Medical University Nanjing China
Department of Occupational Medicine and Environmental Health School of Public Health Key Laboratory of Public Health Safety and Emergency Prevention and Control Technology of Higher Education Institutions in Jiangsu Province Nanjing Medical University Nanjing China
Funding
National Natural Science Foundation of China
References (87)
Show source-provided references
1. 10.1016/j.physbeh.2009.02.02610.1016/j.physbeh.2009.02.026 ↗
2. Puberty Dysregulation And Increased Risk Of Disease In Adult Life: Possible Modes Of Action10.1016/j.reprotox.2013.06.002 ↗
3. 10.1111/andr.1347010.1111/andr.13470 ↗
4. 10.1159/00047187610.1159/000471876 ↗
5. 10.1016/j.dsx.2022.10244710.1016/j.dsx.2022.102447 ↗
6. 10.1093/oxfordjournals.bmb.a07156810.1093/oxfordjournals.bmb.a071568 ↗
7. 10.1016/j.bbr.2021.11359310.1016/j.bbr.2021.113593 ↗
8. 10.3390/nu1616273210.3390/nu16162732 ↗
9. 10.1016/j.etap.2017.02.02410.1016/j.etap.2017.02.024 ↗
10. Endocrine‐Disrupting Chemicals And Male Reproductive Health10.1016/j.rbmo.2013.02.005 ↗
11. Exposure To Endocrine Disruptors During Adulthood: Consequences For Female Fertility10.1530/JOE-17-0023 ↗
12. 10.1073/pnas.211863111910.1073/pnas.2118631119 ↗
13. 10.1073/pnas.171680211510.1073/pnas.1716802115 ↗
14. 10.1126/science.abe824410.1126/science.abe8244 ↗
15. 10.1016/j.arcmed.2004.11.00410.1016/j.arcmed.2004.11.004 ↗
16. 10.1007/s10735‐025‐10463‐x10.1007/s10735‐025‐10463‐x ↗
17. 10.3390/ijms23201211510.3390/ijms232012115 ↗
18. 10.1210/jendso/bvac06810.1210/jendso/bvac068 ↗
19. 10.1146/annurev.physiol.63.1.19310.1146/annurev.physiol.63.1.193 ↗
20. 10.1074/jbc.M110.18843310.1074/jbc.M110.188433 ↗
21. 10.1021/jacs.8b0390110.1021/jacs.8b03901 ↗
22. 10.1371/journal.pone.008392210.1371/journal.pone.0083922 ↗
23. 10.3389/fphar.2024.135290710.3389/fphar.2024.1352907 ↗
24. 10.1016/j.bmcl.2022.12895110.1016/j.bmcl.2022.128951 ↗
25. 10.1016/j.scitotenv.2022.15354810.1016/j.scitotenv.2022.153548 ↗
26. 10.3389/fimmu.2020.57008310.3389/fimmu.2020.570083 ↗
27. 10.1136/bmjopen‐2022‐07082010.1136/bmjopen‐2022‐070820 ↗
28. Cumulative Risk Assessment And Exposure Characteristics Of Parabens In The General Taiwanese Using Multiple Hazard Indices Approaches10.1016/j.scitotenv.2022.156821 ↗
29. The Smoking Estrogens–A Potential Synergy Between Estradiol and benzo (a) pyrene10.1016/j.biopha.2021.111658 ↗
30. 10.1016/j.envint.2017.04.01410.1016/j.envint.2017.04.014 ↗
31. 10.1016/j.jhazmat.2022.12921310.1016/j.jhazmat.2022.129213 ↗
32. 10.1093/humrep/des06910.1093/humrep/des069 ↗
33. 10.1016/j.envpol.2019.11350910.1016/j.envpol.2019.113509 ↗
34. 10.1016/j.envres.2017.01.03310.1016/j.envres.2017.01.033 ↗
35. 10.1016/j.scitotenv.2020.13962610.1016/j.scitotenv.2020.139626 ↗
36. 10.1038/s41598‐022‐15300‐910.1038/s41598‐022‐15300‐9 ↗
37. Electrotopological State Indices For Atom Types: A Novel Combination Of Electronic, Topological, And Valence State Information10.1021/ci00028a014 ↗
38. 10.1016/j.tox.2021.15298510.1016/j.tox.2021.152985 ↗
39. 10.3390/cells1119302910.3390/cells11193029 ↗
40. 10.1155/2016/137652610.1155/2016/1376526 ↗
41. 10.1021/acs.jmedchem.3c0044210.1021/acs.jmedchem.3c00442 ↗
42. 10.1021/acs.jmedchem.9b0184910.1021/acs.jmedchem.9b01849 ↗
43. 10.1016/j.ecoenv.2024.11605410.1016/j.ecoenv.2024.116054 ↗
44. 10.1016/j.ijheh.2018.07.00910.1016/j.ijheh.2018.07.009 ↗
45. 10.1016/j.repbio.2023.10076810.1016/j.repbio.2023.100768 ↗
46. Chronic Exposure To Perfluorohexane Sulfonate Leads To A Reproduction Deficit By Suppressing Hypothalamic Kisspeptin Expression In Mice
47. 10.1016/j.reprotox.2018.09.00610.1016/j.reprotox.2018.09.006 ↗
48. 10.1095/biolreprod.111.09259310.1095/biolreprod.111.092593 ↗
49. 10.1530/joe‐16‐007010.1530/joe‐16‐0070 ↗
50. 10.3389/fendo.2015.0000810.3389/fendo.2015.00008 ↗
51. 10.1095/biolreprod.115.13033610.1095/biolreprod.115.130336 ↗
52. 10.1021/acs.est.2c0535710.1021/acs.est.2c05357 ↗
53. 10.1016/j.heliyon.2024.e3453110.1016/j.heliyon.2024.e34531 ↗
54. Comparison Of Simple Potential Functions For Simulating Liquid Water10.1063/1.445869 ↗
55. Canonical Sampling Through Velocity Rescaling10.1063/1.2408420 ↗
56. 10.1038/s41598‐022‐11925‐y10.1038/s41598‐022‐11925‐y ↗
57. Thyroid Hormone Biomonitoring: A Review on Their Metabolism and Machine‐Learning Based Analysis on Effects of Endocrine Disrupting Chemicals10.1021/envhealth.3c00184 ↗
58. 10.3389/fendo.2022.109665510.3389/fendo.2022.1096655 ↗
59. 10.1038/s41593‐023‐01478‐210.1038/s41593‐023‐01478‐2 ↗
60. 10.1080/1528739050022738110.1080/15287390500227381 ↗
61. 10.1542/peds.2006‐376610.1542/peds.2006‐3766 ↗
62. 10.1016/j.taap.2021.11581410.1016/j.taap.2021.115814 ↗
63. 10.1016/j.tox.2005.01.01210.1016/j.tox.2005.01.012 ↗
64. 10.1016/j.scitotenv.2014.11.08110.1016/j.scitotenv.2014.11.081 ↗
65. 10.1371/journal.pone.009570110.1371/journal.pone.0095701 ↗
66. 10.1016/j.fct.2017.11.00510.1016/j.fct.2017.11.005 ↗
67. 10.1016/j.envres.2024.11822110.1016/j.envres.2024.118221 ↗
68. 10.1093/jat/29.8.81910.1093/jat/29.8.819 ↗
69. 10.1093/annhyg/men06610.1093/annhyg/men066 ↗
70. 10.4161/endo.2506610.4161/endo.25066 ↗
71. 10.1016/j.jare.2025.04.02210.1016/j.jare.2025.04.022 ↗
72. 10.1016/j.molcel.2020.09.02210.1016/j.molcel.2020.09.022 ↗
73. 10.3389/fendo.2025.168460810.3389/fendo.2025.1684608 ↗
74. 10.3389/fpls.2022.86274610.3389/fpls.2022.862746 ↗
75. 10.3390/metabo903005710.3390/metabo9030057 ↗
76. 10.1021/acs.est.9b0247410.1021/acs.est.9b02474 ↗
77. 10.1016/j.jbc.2023.10299910.1016/j.jbc.2023.102999 ↗
78. 10.1158/1535‐7163.Mct‐22‐011510.1158/1535‐7163.Mct‐22‐0115 ↗
79. 10.1021/acs.est.3c0648010.1021/acs.est.3c06480 ↗
80. 10.1111/j.1743‐6109.2011.02265.x10.1111/j.1743‐6109.2011.02265.x ↗
81. Age‐Specific Serum Total and Free Estradiol Concentrations in Healthy Men in US Nationally Representative Samples10.1210/js.2019-00178 ↗
82. The Association Between Testosterone, Estradiol And Their Ratio And Mortality Among US Men10.1111/and.13993 ↗
83. Weisburd D. · 2007 · 161
84. 10.3390/genes1103026810.3390/genes11030268 ↗
85. 10.1093/nar/gkp35610.1093/nar/gkp356 ↗
86. 10.3390/foods1402023210.3390/foods14020232 ↗
87. 10.3389/fnagi.2025.156183110.3389/fnagi.2025.1561831 ↗