Abstract
Telomeres cap the ends of eukaryotic chromosomes to maintain genomic stability and integrity during an organism’s lifespan. The length of telomeres inevitably shortens due to DNA replication, genotoxic agents, and biological aging. A limited number of cell types, e.g., stem cells, germline cells, and early embryos can elongate shortened telomeres via the enzymatic action of telomerase, which is composed of telomerase reverse transcriptase (TERT) and telomerase RNA component (Terc). Additionally, telomere-associated proteins including telomeric repeat binding factor 1 (TRF1) and 2 (TRF2), as well as protection of telomeres 1a (POT1a), bind to telomeres to maintain their structural integrity and length. During ovarian aging in mammals, telomeres progressively shorten, accompanied by fertility loss; however, the molecular mechanism underlying this attrition during follicle development remains unclear. In this study, the primary, secondary, preantral, and antral follicles were obtained either from 6-week-old adult (n = 19) or 52-week-old aged (n = 12) mice. We revealed that the Tert, Terc, Trf1, Trf2, and Pot1a gene expression (P < 0.001) and TERT protein (P < 0.01) levels significantly decreased in certain ovarian follicles of the aged group when compared to those of the adult group. Also, telomerase activity exhibited remarkable changes in the follicles of both groups. Consequently, altered telomere-associated gene expression and reduced TERT protein levels in the follicles of aged mice may be a determinant of telomere shortening during ovarian aging, and infertility appearing in the later decades of reproductive lifespan. Further investigations are required to determine the molecular mechanisms underlying these alterations in the follicles during ovarian aging.
Highlights
Telomeres cap the ends of eukaryotic chromosomes to maintain genomic stability and integrity during an organism’s lifespan
We determined for the first time that the altered Tert, telomerase RNA component (Terc), Trf[1], Trf[2], and Pot1a gene expression, telomerase reverse transcriptase (TERT) protein levels and telomerase activity in the aged ovarian follicles which may mediate shortening of telomeres and loss of fertility during biological a ging[35,36]
That pregnant mare’s serum gonadotropin [PMSG, 10 IU/mL; an FSH analog], enhanced TERT protein and mRNA levels as well as telomerase activity in the rat granulosa c ells[42]. These findings suggest that the fluctuating Tert gene expression in the follicles during aging may arise from altered estradiol and FSH levels as well as from changes in their receptors
Summary
Telomeres cap the ends of eukaryotic chromosomes to maintain genomic stability and integrity during an organism’s lifespan. (TRF1) and 2 (TRF2), protection of telomeres 1a (POT1a), POT1 and TIN2 interacting protein 1 (TPP1), TRF1 interacting nuclear protein 2 (TIN2), and repressor activator protein 1 (RAP1) are exclusively defined as the shelterin complex, which maintains the integrity of chromosome ends and regulates telomere elongation p rocess[8,10]. Among these telomere-associated proteins, the TRF1 and TRF2 proteins bind to the doublestranded part of telomeric sequences in order to maintain their length[11,12]. As POT1 influences telomere length by positively modulating telomerase activity, its absence leads to certain defects related to chromosome pairing and genomic integrity, as a consequence of excessive telomere s hortening[20]
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