Flutamide-induced alterations in transcriptional profiling of neonatal porcine ovaries

Journal of Animal Science and Biotechnology

Patrycja Witek¹  Elzbieta Czaja¹  Katarzyna Knapczyk-Stwora¹  Maria Slomczynska¹  Marek Koziorowski²  Jan P. Jastrzebski³  Lukasz Paukszto³  Anna Nynca⁴  Renata E. Ciereszko⁴ 

[1] Department of Endocrinology, Institute of Zoology and Biomedical Research, Jagiellonian University in Krakow;Department of Physiology and Reproduction of Animals, University of Rzeszow;Department of Plant Physiology, Genetics and Biotechnology, Faculty of Biology and Biotechnology, University of Warmia and Mazury in Olsztyn;Laboratory of Molecular Diagnostics, Faculty of Biology and Biotechnology, University of Warmia and Mazury in Olsztyn;

关键词: Flutamide;    LncRNA;    Ovary;    Pig;    RNA-Seq;    Transcriptome;   

DOI  :  10.1186/s40104-019-0340-y

来源: DOAJ

【 摘 要 】

Abstract Background Androgens are involved in the regulation of ovarian development during fetal/neonatal life. Environmental chemicals displaying anti-androgenic activities may affect multiple signal transduction pathways by blocking endogenous androgen action. The aim of the current study was to examine effects of the anti-androgen flutamide on the expression of coding transcripts and long non-coding RNAs (lncRNAs) in neonatal porcine ovaries. By employing RNA-Seq technology we aimed to extend our understanding of the role of androgens in neonatal folliculogenesis and examine the impact of the anti-androgen flutamide on ovarian function. Method Piglets were subcutaneously injected with flutamide (50 mg/kg BW) or corn oil (controls) between postnatal days 1 and 10 (n = 3/group). Ovaries were excised from the 11-day-old piglets and total cellular RNAs were isolated and sequenced. Results Flutamide-treated piglet ovaries showed 280 differentially expressed genes (DEGs; P-adjusted < 0.05 and log2 fold change ≥1.0) and 98 differentially expressed lncRNAs (DELs; P-adjusted < 0.05 and log2FC ≥ 1.0). The DEGs were assigned to GO term, covering biological processes, molecular functions and cellular components, which linked the DEGs to functions associated with cellular transport, cell divisions and cytoskeleton. In addition, STRING software demonstrated strongest interactions between genes related to cell proliferation. Correlations between DEGs and DELs were also found, revealing that a majority of the genes targeted by the flutamide-affected lncRNAs were associated with intracellular transport and cell division. Conclusions Our results suggest that neonatal exposure of pigs to flutamide alters the expression of genes involved in ovarian cell proliferation, ovarian steroidogenesis and oocyte fertilization, which in turn may affect female reproduction in adult life.

【 授权许可】

Unknown