Transcriptional landscape of mouse-aged ovaries reveals a unique set of non-coding RNAs associated with physiological and environmental ovarian dysfunctions

Danila Cuomo, Immacolata Porreca, Michele Ceccarelli, David W. Threadgill, William T. Barrington, Annacristina Petriella, Fulvio D’Angelo, Gilda Cobellis, Francesca De Stefano, Maria N. D’Agostino, Mario De Felice, Massimo Mallardo, Concetta Ambrosino

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The progressive and physiological decline in ovarian function depends on the rate of follicular loss by atresia, contributing to the reduction in ovarian reserve. Genetics and environmental factors play important roles in ovarian senescence and in the onset of ovarian dysfunctions such as diminished ovarian reserve. A better understanding of the mechanisms underlying ovarian aging and their regulation by genetic and environmental factors is needed to evaluate ovarian reserve and to predict fertility potential by identification of more accurate and less invasive markers. We report transcriptomic data (i) implicating novel (e.g. EIF2 signalling) and well-known pathways (e.g. TGFβ signalling), and (ii) defining a unique set of non-coding RNA (ncRNA), both associated with ovarian function. The latter includes miRNAs (e.g. Mir143 and Mir145), snoRNAs (e.g. Snord16a and Snora34), and one lncRNA (Gas5), which are differentially expressed in middle-aged ovaries (12 months) vs young-aged (3 months) from CD1 mice. Experimental analysis confirms that ovary lifespan varies across genetic backgrounds in mice and, genetics influences the response to environmental perturbations such as diet. Moreover, the identified ncRNAs were verified in a model of reproductive dysfunction promoted by the environmental toxicant ethylenthiourea. We also report the increase of miRNA143 and miRNA145 in follicular fluid of women with diminished ovarian reserve. Their levels inversely correlate with the hormonal profile and with the number of the oocytes recruited upon hormonal stimulation. Overall, we report a transcriptomic signature for ovarian dysfunction in vivo that provides a valuable resource for translational research in human reproductive aging.

Original languageEnglish
Article number112
JournalCell Death Discovery
Volume4
Issue number1
DOIs
Publication statusPublished - 1 Dec 2018

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Untranslated RNA
Ovary
Follicular Atresia
Eukaryotic Initiation Factor-2
Small Nucleolar RNA
Long Noncoding RNA
Follicular Fluid
Translational Medical Research
MicroRNAs
Oocytes
Fertility
Diet
Ovarian Reserve

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

Cite this

Transcriptional landscape of mouse-aged ovaries reveals a unique set of non-coding RNAs associated with physiological and environmental ovarian dysfunctions. / Cuomo, Danila; Porreca, Immacolata; Ceccarelli, Michele; Threadgill, David W.; Barrington, William T.; Petriella, Annacristina; D’Angelo, Fulvio; Cobellis, Gilda; De Stefano, Francesca; D’Agostino, Maria N.; De Felice, Mario; Mallardo, Massimo; Ambrosino, Concetta.

In: Cell Death Discovery, Vol. 4, No. 1, 112, 01.12.2018.

Research output: Contribution to journalArticle

Cuomo, D, Porreca, I, Ceccarelli, M, Threadgill, DW, Barrington, WT, Petriella, A, D’Angelo, F, Cobellis, G, De Stefano, F, D’Agostino, MN, De Felice, M, Mallardo, M & Ambrosino, C 2018, 'Transcriptional landscape of mouse-aged ovaries reveals a unique set of non-coding RNAs associated with physiological and environmental ovarian dysfunctions', Cell Death Discovery, vol. 4, no. 1, 112. https://doi.org/10.1038/s41420-018-0121-y
Cuomo, Danila ; Porreca, Immacolata ; Ceccarelli, Michele ; Threadgill, David W. ; Barrington, William T. ; Petriella, Annacristina ; D’Angelo, Fulvio ; Cobellis, Gilda ; De Stefano, Francesca ; D’Agostino, Maria N. ; De Felice, Mario ; Mallardo, Massimo ; Ambrosino, Concetta. / Transcriptional landscape of mouse-aged ovaries reveals a unique set of non-coding RNAs associated with physiological and environmental ovarian dysfunctions. In: Cell Death Discovery. 2018 ; Vol. 4, No. 1.
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