@misc{10481/80323,
year = {2023},
month = {1},
url = {https://hdl.handle.net/10481/80323},
abstract = {Background: Kisspeptin has been proposed as an effect biomarker to understand the mechanisms by which some environmental
chemicals adversely affect the human reproductive system.
Objective: To ascertain whether kisspeptin serum protein and DNA methylation levels are associated with exposure to
several environmental chemicals (individually and as a mixture) and serum reproductive hormone levels in adolescent
males.
Methods: Three phenols (bisphenol A [BPA], methyl-paraben [MPB], and benzophenone-3 [BP3]); two toxic metals
(arsenic and cadmium); and four metabolites of non-persistent pesticides, including insecticides (2-isopropyl-6-
methyl-4-pyrimidinol [IMPy], malathion diacid [MDA], and dimethylcyclopropane carboxylic acid [DCCA]) and fungicides
(ethylene thiourea [ETU]) were measured in first-morning urine samples of 133 adolescent males aged 15–17
years from the INMA-Granada cohort. In blood samples collected on the same day, KISS1 gene DNA methylation was
measured at four CpGs from the Exon IV, as well as serumlevels of kiss54 protein, total testosterone (T), estradiol (E2), sex hormone binding-globulin, dehydroepiandrosterone sulfate, luteinizing hormone (LH), and follicle-stimulating
hormone (FSH). Multiple linear regression and mixture (quantile g-computation) models were fit.
Results: UrinaryMDA and DCCA concentrations were associatedwith higher kiss54 levels [%change (95%CI) for each
log-unit increase in concentration = 2.90 (0.32;5.56), and 1.93 (0.45,3.43), respectively]; IMPy with lower DNA
methylation percentage at CpG1 and total CpGs [% change (95%CI) = −1.15 (−1.96;-0.33): −0.89 (−1.73;-
0.01), respectively]; and BP3 and DCCA with lower total CpGs methylation [−0.53 (−1.04;-0.01) and − 0.69
(−1.37;-0.01), respectively]. The pesticide mixture and the whole chemical mixture were associated with higher
kiss54 [% change (95%CI) = 9.09 (3.29;15.21) and 11.61 (3.96;19.82), respectively] and lower methylation levels
at several CpGs. Additionally, serum kiss54 in the third tertile was associated with higher LH levels [% change
(95%CI) = 28.69 (3.75–59.63)], and third-tertile CpG1, CpG2, and total CpG methylation percentages were associated
with lower FSH and E2.
Conclusion: The findings of the present study and the negative correlation between serumkiss54 levels and KISS1 DNA
methylation percentages suggested that kisspeptin may be a promising effect biomarker.},
organization = {European Union's Horizon 2020 research and innovation program	733032	
CP16/00085},
organization = {Instituto de Salud Carlos III	PI 17/01526	
PT17/0019},
organization = {Human Genotyping Laboratory at the Spanish National Cancer Research Centre	UCE-PP2017-06},
organization = {Instituto de Salud Carlos III
European Commission		
European Commission},
organization = {Biomedical Research Networking Center-CIBER de Epidemiologia y Salud Publica (CIBERESP)},
organization = {University of Granada	CPII21/00014},
organization = {Ramon Areces Foundation},
organization = {Miguel Servet Type II program of the ISCIII},
organization = {European Commission},
organization = {Spanish Government},
publisher = {Elsevier},
keywords = {Kisspeptin},
keywords = {Effect biomarker},
keywords = {Xenobiotic mixtures},
keywords = {Endocrine disrupting chemicals},
keywords = {HBM4EU},
title = {Kisspeptin as potential biomarker of environmental chemical mixture effect on reproductive hormone profile: A pilot study in adolescent males},
doi = {10.1016/j.scitotenv.2023.161668},
author = {Rodríguez Carrillo, Andrea and Remy, Sylvie and Salamanca Fernández, Elena and Gil Hernández, Fernando and Olmedo Palma, Pablo and Mustieles Miralles, Vicente and Vela Soria, Fernando and Olea Serrano, Nicolás and Fernández Cabrera, Mariana Fátima and Freire, Carmen},
}