Urinary phthalate metabolites and small non-coding RNAs from seminal plasma extracellular vesicles among men undergoing infertility treatment.

Autor: Oluwayiose OA; C.S. Mott Center for Human Growth and Development, Department of Obstetrics and Gynecology, School of Medicine, Wayne State University, Detroit, MI, 48201, USA., Houle E; C.S. Mott Center for Human Growth and Development, Department of Obstetrics and Gynecology, School of Medicine, Wayne State University, Detroit, MI, 48201, USA., Whitcomb BW; Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts Amherst, 715 North Pleasant Street, Amherst, MA, USA., Suvorov A; Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts Amherst, 686 North Pleasant Street, Amherst, MA, USA., Rahil T; Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, UMass Chan-Baystate, 759 Chestnut Street, Springfield, MA, USA., Sites CK; Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, UMass Chan-Baystate, 759 Chestnut Street, Springfield, MA, USA., Krawetz SA; C.S. Mott Center for Human Growth and Development, Department of Obstetrics and Gynecology, School of Medicine, Wayne State University, Detroit, MI, 48201, USA; Center for Molecular Medicine and Genetics, Wayne State School of Medicine, USA., Visconti PE; Department of Veterinary and Animal Sciences, University of Massachusetts Amherst, 661 N. Pleasant St, Amherst, MA, 01003, USA., Pilsner JR; C.S. Mott Center for Human Growth and Development, Department of Obstetrics and Gynecology, School of Medicine, Wayne State University, Detroit, MI, 48201, USA; Institute of Environmental Health Sciences, Wayne State University, Detroit, MI, 48201, USA. Electronic address: rpilsner@wayne.edu.
Jazyk: angličtina
Zdroj: Environmental pollution (Barking, Essex : 1987) [Environ Pollut] 2023 Jul 15; Vol. 329, pp. 121529. Date of Electronic Publication: 2023 Mar 30.
DOI: 10.1016/j.envpol.2023.121529
Abstrakt: Non-coding RNA (ncRNA) cargo of extracellular vesicles (EVs) in the male reproductive tract play critical roles in semen quality and emerging evidence suggests their susceptibility to environmental factors. Male phthalate exposures have been linked to poor semen quality, sperm DNA methylation profiles and embryo development; however, there is limited evidence on their potential impact on EV ncRNAs profiles. We evaluated the association between urinary phthalate metabolites and small ncRNAs (sncRNAs) of seminal plasma EVs (spEV) among men receiving clinical infertility care. We conducted sncRNA sequencing of EVs in 96 seminal plasma samples collected from the Sperm Environmental Epigenetics and Development Study (SEEDS). Sequencing reads were mapped to human transcriptome databases using STAR. Urinary metabolite concentrations of thirteen phthalates and two DiNCH, a phthalate alternative, were measured via tandem mass spectrometry. Associations with normalized counts were assessed using EdgeR (FDR<0.05) adjusting for urinary dilution via specific gravity, age, BMI, batch, and biotype-specific total counts. Select metabolites, MEOHP, MECPP, ∑DEHP, MCPP, MCNP, MCOP, were negatively (p < 0.05) correlated with miRNA relative abundance. Similarly, nine metabolites including MEOHP, MECPP, MEHP, MCPP, MHBP, MHiNCH, MiBP, MEHHP, MCOP and ∑DEHP were associated (q < 0.05) with normalized counts from 23 unique ncRNA transcripts (7 miRNAs (pre & mature); 6 tRFs; and 10 piRNAs), most (78%) of which displayed increased expression patterns. miRNA and tRFs gene targets were enriched in vesicle-mediated transport and developmental-related ontology terms, such as tyrosine kinase, head development, and cell morphogenesis. Six genes (MAPK1, BMPR1A/2, PTEN, TGFBR2, TP53 and APP) were present in all the ontology terms and predicted to form protein association networks. piRNAs were annotated to pseudogenes of genes important in EV cargo transfer and embryonic development. This is the first study to associate phthalate exposures to altered spEV sncRNA profiles. Future studies are needed to determine their impact on reproductive outcomes.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023. Published by Elsevier Ltd.)
Databáze: MEDLINE
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