Transgenerational Transmission of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) Effects in Human Granulosa Cells: The Role of MicroRNAs

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 Jan 23

PMID 38256218

Authors

Laura Gaspari

Delphine Haouzi

Aurelie Gennetier

Gaby Granes

Alexandra Soler

Charles Sultan

Francoise Paris

Samir Hamamah

Affiliations

Soon will be listed here.

Abstract

Endocrine-disrupting chemicals (EDCs) might contribute to the increase in female-specific cancers in Western countries. 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD) is considered the "prototypical toxicant" to study EDCs' effects on reproductive health. Epigenetic regulation by small noncoding RNAs (sncRNAs), such as microRNAs (miRNA), is crucial for controlling cancer development. The aim of this study was to analyze transcriptional activity and sncRNA expression changes in the KGN cell line after acute (3 h) and chronic (72 h) exposure to 10 nM TCDD in order to determine whether sncRNAs' deregulation may contribute to transmitting TCDD effects to the subsequent cell generations (day 9 and day 14 after chronic exposure). Using Affymetrix GeneChip miRNA 4.0 arrays, 109 sncRNAs were found to be differentially expressed (fold change < -2 or >2; -value < 0.05) between cells exposed or not (control) to TCDD for 3 h and 72 h and on day 9 and day 14 after chronic exposure. Ingenuity Pathway Analysis predicted that following the acute and chronic exposure of KGN cells, sncRNAs linked to cellular development, growth and proliferation were downregulated, and those linked to cancer promotion were upregulated on day 9 and day 14. These results indicated that TCDD-induced sncRNA dysregulation may have transgenerational cancer-promoting effects.

Citing Articles

Impact of Endocrine Disruptors on the Genitourinary Tract.

Caneparo C, Carignan L, Lonina E, Goulet S, Pellerin F, Chabaud S J Xenobiot. 2024; 14(4):1849-1888.

PMID: 39728407 PMC: 11676856. DOI: 10.3390/jox14040099.

References

Valleron W, Laprevotte E, Gautier E, Quelen C, Demur C, Delabesse E . Specific small nucleolar RNA expression profiles in acute leukemia. Leukemia. 2012; 26(9):2052-60. DOI: 10.1038/leu.2012.111. View

Jablonska O, Piasecka-Srader J, Nynca A, Kolomycka A, Robak A, Wasowska B . 2,3,7,8-Tetrachlorodibenzo-p-dioxin alters steroid secretion but does not affect cell viability and the incidence of apoptosis in porcine luteinised granulosa cells. Acta Vet Hung. 2014; 62(3):408-21. DOI: 10.1556/AVet.2014.015. View

Sopo M, Anttila M, Hamalainen K, Kivela A, Yla-Herttuala S, Kosma V . Expression profiles of VEGF-A, VEGF-D and VEGFR1 are higher in distant metastases than in matched primary high grade epithelial ovarian cancer. BMC Cancer. 2019; 19(1):584. PMC: 6570919. DOI: 10.1186/s12885-019-5757-3. View

Wojtowicz A, Tomanek M, Augustowska K, Gregoraszczuk E . Aromatic hydrocarbon receptor (AhR) in the porcine theca and granulosa cells: effect of TCDD, PCB 126 and PCB 153 on the expression of AhR. Endocr Regul. 2006; 39(4):109-18. View

Huumonen K, Korkalainen M, Viluksela M, Lahtinen T, Naarala J, Juutilainen J . Role of microRNAs and DNA Methyltransferases in Transmitting Induced Genomic Instability between Cell Generations. Front Public Health. 2014; 2:139. PMC: 4163984. DOI: 10.3389/fpubh.2014.00139. View

Orlowska K, Swigonska S, Sadowska A, Ruszkowska M, Nynca A, Molcan T . The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the proteome of porcine granulosa cells. Chemosphere. 2018; 212:170-181. DOI: 10.1016/j.chemosphere.2018.08.046. View

Jablonska O, Piasecka J, Ostrowska M, Sobocinska N, Wasowska B, Wasowka B . The expression of the aryl hydrocarbon receptor in reproductive and neuroendocrine tissues during the estrous cycle in the pig. Anim Reprod Sci. 2011; 126(3-4):221-8. DOI: 10.1016/j.anireprosci.2011.05.010. View

Huang W, Sun Y, Pan Q, Fang K, Chen X, Zeng Z . The snoRNA-like lncRNA LNC-SNO49AB drives leukemia by activating the RNA-editing enzyme ADAR1. Cell Discov. 2022; 8(1):117. PMC: 9622897. DOI: 10.1038/s41421-022-00460-9. View

Ruszkowska M, Sadowska A, Nynca A, Orlowska K, Swigonska S, Molcan T . The effects of 2,3,7,8-tetrachlorodibenzo--dioxin (TCDD) on the transcriptome of aryl hydrocarbon receptor (AhR) knock-down porcine granulosa cells. PeerJ. 2020; 8:e8371. PMC: 6982409. DOI: 10.7717/peerj.8371. View

10.

Chaffin C, Heimler I, Rawlins R, Wimpee B, Sommer C, Hutz R . Estrogen receptor and aromatic hydrocarbon receptor in the primate ovary. Endocrine. 2010; 5(3):315-21. DOI: 10.1007/BF02739065. View

11.

Patino-Garcia D, Cruz-Fernandes L, Bunay J, Orellana R, Moreno R . Daily exposure to phthalates and alkylphenols alters miR biogenesis and expression in mice ovaries. J Mol Endocrinol. 2020; 65(4):175-186. DOI: 10.1530/JME-20-0149. View

12.

Bunkar N, Pathak N, Lohiya N, Mishra P . Epigenetics: A key paradigm in reproductive health. Clin Exp Reprod Med. 2016; 43(2):59-81. PMC: 4925870. DOI: 10.5653/cerm.2016.43.2.59. View

13.

Eskenazi B, Warner M, Marks A, Samuels S, Needham L, Brambilla P . Serum dioxin concentrations and time to pregnancy. Epidemiology. 2010; 21(2):224-31. PMC: 6267871. DOI: 10.1097/EDE.0b013e3181cb8b95. View

14.

Enan E, Moran F, VandeVoort C, Stewart D, Overstreet J, Lasley B . Mechanism of toxic action of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in cultured human luteinized granulosa cells. Reprod Toxicol. 1996; 10(6):497-508. DOI: 10.1016/s0890-6238(96)00137-2. View

15.

Zhang Y, Yao C, Ju Z, Jiao D, Hu D, Qi L . Krüppel-like factors in tumors: Key regulators and therapeutic avenues. Front Oncol. 2023; 13:1080720. PMC: 9905823. DOI: 10.3389/fonc.2023.1080720. View

16.

Eskenazi B, Warner M, Brambilla P, Signorini S, Ames J, Mocarelli P . The Seveso accident: A look at 40 years of health research and beyond. Environ Int. 2018; 121(Pt 1):71-84. PMC: 6221983. DOI: 10.1016/j.envint.2018.08.051. View

17.

Rogers R, Chai S, Pask A, Mattiske D . Prenatal exposure to diethylstilbestrol has long-lasting, transgenerational impacts on fertility and reproductive development. Toxicol Sci. 2023; 195(1):53-60. PMC: 10464516. DOI: 10.1093/toxsci/kfad066. View

18.

Ernst J, Jann J, Biemann R, Koch H, Fischer B . Effects of the environmental contaminants DEHP and TCDD on estradiol synthesis and aryl hydrocarbon receptor and peroxisome proliferator-activated receptor signalling in the human granulosa cell line KGN. Mol Hum Reprod. 2014; 20(9):919-28. DOI: 10.1093/molehr/gau045. View

19.

Cherukunnath A, Davargaon R, Ashraf R, Kamdar U, Srivastava A, Tripathi P . KLF8 is activated by TGF-β1 via Smad2 and contributes to ovarian cancer progression. J Cell Biochem. 2022; 123(5):921-934. DOI: 10.1002/jcb.30235. View

20.

Xu L, Xiang J, Shen J, Zou X, Zhai S, Yin Y . Oncogenic MicroRNA-27a is a target for genistein in ovarian cancer cells. Anticancer Agents Med Chem. 2013; 13(7):1126-32. DOI: 10.2174/18715206113139990006. View