مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
Umbilical cord blood thyroid hormones are inversely related to telomere length and mitochondrial DNA copy number
Umbilical cord blood thyroid hormones are inversely related to telomere length and mitochondrial DNA copy number
homa ohadi,1parvin khalili,2farzaneh abasnezhad kasrineh,3ozra sadat esmaeili,4faeze esmaeili ranjbar,5zahra jalali,6,*
1. Department of Clinical Biochemistry, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran 2. Social Determinants of Health Research Centre, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.Department of Epidemiology, School of Public Health, Iran University of Medical Sciences, Tehran, Iran. 3. Department of Clinical Biochemistry, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran. 4. Department of Clinical Biochemistry, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran. 5. Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran 6. Department of Clinical Biochemistry, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran. Zahra.jalali@mail.mcgill.ca.Non-Communicable Diseases Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
Introduction: Hypothyroidism has been linked to reduced mortality rate and increased lifespan and health span. Telomere shortening, enhanced oxidative stress, and reduced cellular mitochondrial content are important hallmarks of aging shown to be related to age-associated diseases. It was proposed that the status of these markers in early life can be predictive of lifespan and the predisposition to certain age-associated disease in adulthood. Animal studies indicated that prenatal injection of thyroid hormones affects postnatal telomere length.
Methods: Here, we sought to determine whether thyroid hormones TSH and fT4 are related to the telomere length, mitochondrial DNA copy number (mtDNAcn), and oxidative stress resistance marker GPX in the cord blood of newborns. In this study, we analyzed 70 mothers (18-42 years) and neonate dyads born in 2022 at the Nik Nafs maternity Hospital in Rafsanjan. The relative telomere length (RTL) and mtDNAcn were measured in the genomic DNA of cord blood leukocytes using real-time PCR. GPX enzyme activity was measured in the serum using colorimetric assays. In this study the correlation between these markers and the cord blood TSH and fT4 hormones were assessed using regression models.
Results: We found a reverse relationship between TSH levels and RTL in the cord blood of neonates. Additionally, our results displayed increased TSH levels associated with enhanced GPX activity. Regarding the mitochondrial DNA copy number, we found an indirect relationship between fT4 level and mtDNAcn only in male newborns. Future analyses of various oxidative stress markers, mitochondrial biogenesis status, telomerase activity, and the level of DNA damage are warranted to demonstrate the underlying mechanism of our observations.
Conclusion: Overall, our study indicated a reverse relationship between cord blood leukocytes telomere length and serum
TSH levels, accompanied by increased GPX activity. In addition, we observed lower levels of mitochondrial
DNA copy number in association with higher fT4 thyroid hormone. Our results provide data on the effects of
the level of prenatal thyroid hormones on age-related factors which will potentially exert life-long influence on
the individual’s health. Therefore, our data implicates the importance of tightly regulating the level of TSH and
fT4 during pregnancy and suggest the transgenerational effects of thyroid hormones on aging. Future follow-up
studies on larger population sizes are required to validate our findings. The underlying molecular mechanism
of the relation between thyroid hormones and molecular aging parameters can be better understood by future
analyses that provide a comprehensive view of the status of various oxidative stress markers, mitochondrial
biogenesis status, telomerase activity, and the level of DNA damage.