Mitochondrial translocation of human telomerase reverse transcriptase in cord blood mononuclear cells of newborns with gestational diabetes mellitus mothers.
OBJECTIVE
To better understand the role of oxidative stress in fetal programming, we assessed the hypothesis that the mitochondrial translocation of human telomerase reverse transcriptase (hTERT) could protect neonatal mitochondrial DNA (mtDNA) from oxidative damage during pregnancies complicated by gestational diabetes mellitus (GDM).


METHODS
26 GDM mothers and 47 controls and their newborns were enrolled. The plasma levels of 8-isoprostaglandin F(2α) in maternal and cord blood were measured to evaluate oxidative stress. Western blotting was then used to assess the mitochondrial localization of hTERT in cord blood mononuclear cells (CBMCs). Finally, the relative mtDNA content was analyzed by real-time PCR.


RESULTS
GDM mothers and their newborns had significantly higher levels of oxidative stress than controls. hTERT was localized in both the nuclei and mitochondria of CBMCs, and the increased CBMC mitochondrial hTERT levels were significantly correlated with elevated oxidative stress in newborns. The neonatal mtDNA content in the GDM group was comparable to controls, and was positively correlated with mitochondrial hTERT levels in CBMCs, suggesting that mitochondrial hTERT in CBMCs may have a protective effect on neonatal mtDNA in GDM pregnancies.


CONCLUSIONS
This study is the first to suggest that the mitochondrial translocation of hTERT in CBMCs under heightened oxidative stress might protect neonatal mtDNA from oxidative damage in GDM pregnancies. This could be an in utero adaptive response of a fetus that is suffering from elevated oxidative stress, and could help our understanding of the roles of oxidative stress in fetal programming.
Department of Pediatrics, West China Second University Hospital, Sichuan University, No. 17, People's South Road, Chengdu 610041, Sichuan Province, PR China; Laboratory of Early Developmental and Injuries, West China Institute of Woman and Children's Health, West China Second University Hospital, Sichuan University, PR China; Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, PR China.
Ping
P
Li
Laboratory of Early Developmental and Injuries, West China Institute of Woman and Children's Health, West China Second University Hospital, Sichuan University, PR China; Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, PR China.
Yu
Y
Tong
Department of Pediatrics, West China Second University Hospital, Sichuan University, No. 17, People's South Road, Chengdu 610041, Sichuan Province, PR China.
Huiming
H
Yang
Department of Obstetrics, West China Second University Hospital, Sichuan University, No. 17, People's South Road, Chengdu 610041, Sichuan Province, PR China.
Shu
S
Zhou
Department of Pediatrics, West China Second University Hospital, Sichuan University, No. 17, People's South Road, Chengdu 610041, Sichuan Province, PR China.
Fei
F
Xiong
Department of Pediatrics, West China Second University Hospital, Sichuan University, No. 17, People's South Road, Chengdu 610041, Sichuan Province, PR China.
Tingzhu
T
Huo
Laboratory of Early Developmental and Injuries, West China Institute of Woman and Children's Health, West China Second University Hospital, Sichuan University, PR China; Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, PR China; Chengdu Women's and Children's Central Hospital, No. 1617, Riyue Avenue, Chengdu 610091, Sichuan Province, PR China. Electronic address: tina_mao1225@163.com.
Meng
M
Mao
D000328:Adult; D016241:Child of Impaired Parents; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D016640:Diabetes, Gestational / Q000097:blood*; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D047109:Fetal Development; D006801:Humans; D007231:Infant, Newborn; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D011247:Pregnancy; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*
D004272:DNA, Mitochondrial; C509186:TERT protein, human; D019098:Telomerase
Fetal programming; Gestational diabetes; Mitochondrial hTERT; Oxidative stress