Downregulation of autophagy gene expression in endometria from women with polycystic ovary syndrome
2017
Authors:
Šumarac-Dumanović, MirjanaApostolović, Milica
Janjetović, Kristina
Jeremić, Danka
Popadić, Dušan
Ljubić, Aleksandar
Micić, Jelena
Dukanac-Stamenković, Jelena
Tubić, Aleksandra
Stevanović, Darko
Micić, Dragan
Trajković, Vladimir
Document Type:
Article (Accepted Version)
Metadata
Show full item recordAbstract:
Autophagy, a process of controlled cellular self-digestion, could be involved in cyclic remodeling
of the human endometrium. We investigated endometrial mRNA expression of 23 autophagyrelated
(ATG) genes and transcription factors in healthy controls (n = 12) and anovulatory
polycystic ovary syndrome (PCOS) patients (n = 24), as well as in their subgroup (n = 12) before
and after metformin treatment. The mRNA levels of transcription factor forkhead box protein O1
(FOXO1) and several molecules involved in autophagosome formation (ATG13, RB1-inducible
coiled-coil 1), autophagosome nucleation (ATG14, beclin 1, SH3-domain GRB2-like endophilin
B1), autophagosome elongation (ATG3, ATG5, g-aminobutyric acid receptor-associated protein -
GABARAP), and delivery of ubiquitinated proteins to autophagosomes (sequestosome 1), were
significantly reduced in anovulatory PCOS compared to healthy endometrium. Free androgen
index, but not free estrogen index, insulin levels, or BMI, negatively correlated with the
endometrial expression of ATG3, ATG14, and GABARAP in PCOS patients. Treatment of
PCOS patients with metformin (2 g/day for 3 months) significantly increased the endometrial
mRNA levels of FOXO1, ATG3, and UV radiation resistance-associated gene. These data
suggest that increased androgen availability in PCOS is associated with metformin-sensitive
transcriptional downregulation of endometrial autophagy
Note:
This is a peer-reviewed version of the following article: Sumarac-Dumanovic, M., Apostolovic, M., Janjetovic, K., Jeremic, D., Popadic, D., Ljubic, A., Micic, J., Dukanac-Stamenkovic, J., Tubic, A., Stevanovic, D., Micic, D., Trajkovic, V., Downregulation of autophagy gene expression in endometria from women with polycystic ovary syndrome, Molecular and Cellular Endocrinology (2016). http://dx.doi.org/10.1016/j.mce.2016.11.009
Keywords:
polycystic ovary sindrome; endometrium; autophagy; autophagy-related genes; free androgen indexSource:
Molecular and Cellular Endocrinology, 2017, 440, 116-124Funding / projects:
- Merck Serono GmbH (Darmstadt, Germany)
- Research of endocrine regulatory mechanisms, markers of systemic inflammation and cardiovascular risk factors in metabolic disorders (RS-MESTD-Basic Research (BR or ON)-175067)
- Modulation of intracellular energy balance-controlling signalling pathways in therapy of cancer and neuro-immuno-endocrine disorders (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41025)
DOI: 10.1016/j.mce.2016.11.009
ISSN: 0303-7207
PubMed: 27845161