Decreased expression of TERT and telomeric proteins as human ovaries age may cause telomere shortening
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REPRODUCTIVE PHYSIOLOGY AND DISEASE
Decreased expression of TERT and telomeric proteins as human ovaries age may cause telomere shortening Fatma Uysal 1,2 & Esra Gozde Kosebent 1 & Havva Serap Toru 3 & Saffet Ozturk 1 Received: 15 April 2020 / Accepted: 18 August 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Objective Telomeres are repetitive sequences localized at the ends of eukaryotic chromosomes comprising noncoding DNA and telomere-binding proteins. TRF1 and TRF2 both bind to the double-stranded telomeric DNA to regulate its length throughout the lifespan of eukaryotic cells. POT1 interacts with single-stranded telomeric DNA and contributes to protecting genomic integrity. Previous studies have shown that telomeres gradually shorten as ovaries age, coinciding with fertility loss. However, the molecular background of telomere shortening with ovarian aging is not fully understood. Methods The present study aimed to determine the spatial and temporal expression levels of the TERT, TRF1, TRF2, and POT1 proteins in different groups of human ovaries: fetal (n = 11), early postnatal (n = 10), premenopausal (n = 12), and postmenopausal (n = 14). Also, the relative telomere signal intensity of each group was measured using the Q-FISH method. Results We found that the telomere signal intensities decreased evenly and significantly from fetal to postmenopausal groups (P < 0.05). The TERT, TRF1, TRF2, and POT1 proteins were localized in the cytoplasmic and nuclear regions of the oocytes, granulosa and stromal cells. Furthermore, the expression levels of these proteins reduced significantly from fetal to postmenopausal groups (P < 0.05). Conclusion These findings suggest that decreased TERT and telomere-binding protein expression may underlie the telomere shortening of ovaries with age, which may be associated with female fertility loss. Further investigations are required to elicit the molecular mechanisms regulating the gradual decrease in the expression of TERT and telomere-binding proteins in human oocytes and granulosa cells during ovarian aging. Keywords Ovarian aging . Telomere . TERT . Telomere-binding proteins
Introduction Telomeres are repetitive noncoding DNA sequences localized at the ends of eukaryotic chromosomes that consist primarily of telomeric DNA and telomere-binding proteins [1]. Telomeric DNA is composed of a long array of doublestranded TTAGGG repeats and a single-stranded 3′ overhang. The 3′ overhang enters the double-stranded telomeric duplex to create T- and D-loop structures. Telomeres are directly * Saffet Ozturk [email protected] 1
Department of Histology and Embryology, Akdeniz University School of Medicine, Campus, 07070 Antalya, Turkey
2
Department of Histology and Embryology, Ankara University School of Medicine, Ankara, Turkey
3
Department of Pathology, Akdeniz University School of Medicine, Antalya, Turkey
bound by telomere repeat-binding factors including telomeric repeat-binding factor 1 (TRF1), telomeric repeat-binding factor 2 (TRF2),
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