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. 2024 Dec 16:15:1490336.
doi: 10.3389/fendo.2024.1490336. eCollection 2024.

Decreased telomerase activity and shortened telomere length in infants whose mothers have gestational diabetes mellitus and increased severity of telomere shortening in male infants

Shuhua Liu #  1   2   3 , Liping Xu #  4 , Yan Cheng #  4 , Dehong Liu  1   2   3 , Bin Zhang  1   2   3 , Xianxia Chen  1   2   3 , Mingming Zheng  1   2   3
Affiliations

Decreased telomerase activity and shortened telomere length in infants whose mothers have gestational diabetes mellitus and increased severity of telomere shortening in male infants

Shuhua Liu et al. Front Endocrinol (Lausanne). .

Abstract

Objective: Gestational diabetes mellitus (GDM) is a common complication during pregnancy and increases the risk of metabolic diseases in offspring. We hypothesize that the poor intrauterine environment in pregnant women with GDM may lead to chromosomal DNA damage and telomere damage in umbilical cord blood cells, providing evidence of an association between intrauterine programming and increased long-term metabolic disease risk in offspring.

Methods: We measured telomere length (TL), serum telomerase (TE) activity, and oxidative stress markers in umbilical cord blood mononuclear cells (CBMCs) from pregnant women with GDM (N=200) and healthy controls (Ctrls) (N=200) and analysed the associations of TL with demographic characteristics, biochemical indicators, and blood glucose levels.

Results: The length of telomeres in umbilical CBMCs in the GDM group was significantly shorter than that in the Ctrl group (P<0.001), and the shortening of telomeres in male infants in the GDM group was more significant than that in the Ctrl group (P<0.001) after adjustment for Pre-pregnancy body mass index (PBMI), Pregnancy weight gain (PGW), and Triglyceride (TG) as confounding factors. In addition, the TE expression level in the GDM group was lower after adjustment. There was no statistically significant difference in oxidative stress hydroxydeoxyguanosine (8-OHdG), malondialdehyde (MDA) and superoxide dismutase (SOD) between the two groups. TL was positively correlated with TE activity, and both were negatively correlated with blood glucose levels. There was no correlation between TL and Gestational age (GA), PBMI, PGW, or TG levels.

Conclusion: The poor intrauterine environment in pregnant women with GDM increases telomere attrition and reduces TE activity, which may be potential genetic risk factors for an increased risk of metabolic diseases in offspring later in life due to intrauterine reprogramming.

Keywords: GDM; TE; TL; gestational diabetes mellitus; telomerase; telomere length.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flowchart of the research object.
Figure 2
Figure 2
Comparison of the relative TL of umbilical CBMC in GDM group and Ctrl group.(*** for P<0.001) There was a significant statistical difference in relative telomere length between the two groups (0.69±0.22 vs. 0.77±0.19, P < 0.001). By adjusting for PBMI, PWG, and TG, there were still differences between the two groups (P<0.001).(*** for P<0.001, Ctrl for healthy control).
Figure 3
Figure 3
Comparison of umbilical cord blood relative TL between GDM group and Ctrl group offspring male infants. There were statistically significant differences in the relative TL between the two groups (0.68±0.22 vs. 0.78±0.17, P < 0.001), and the differences were still statistically significant after adjusting for PBMI, PWG, and TG (P<0.001).(*** for P<0.001,Ctrl for healthy control).
Figure 4
Figure 4
Comparison of umbilical cord blood relative TL of GDM group and Ctrl group offspring of female infants. There was a statistically significant difference in the relative TL between the two groups (0.71±0.23 vs. 0.76±0.22, P=0.028), and the difference was still statistically significant after adjusting for PBMI, PWG, and TG (P=0.322).(* for P<0.05, Ctrl for healthy control).
Figure 5
Figure 5
Correlation analysis between cord blood relative TL and clinical indicators. As shown in figure , the relative TL in umbilical cord blood was negatively correlated with FPG (r = -0.140, P = 0.021), and there was no correlation with the statistical differences between PBMI, Maternal age, PWG and TG (all p>0.05). (* for P<0.05).
Figure 6
Figure 6
Comparison of oxidative stress indexes in umbilical cord blood between GDM patients and healthy control patients. As shown in figure, although the expression levels of 8-OHdG, MDA, AND SOD in the umbilical cord blood of GDM patients increased, no statistical difference was found (all P>0.05).
Figure 7
Figure 7
Comparison of cord blood telomerase expression levels between GDM group and Ctrl group. The expression level of TE in cord blood of GDM offspring was significantly lower than that of Ctrl group (10.43±1.80 vs. 16.24±1.53, P<0.001), and the difference was still statistically significant after adjusting for PBMI, PWG, TG (P<0.001).(*** for P<0.001,TE for telomerase, Ctrl for healthy control).
Figure 8
Figure 8
Correlation analysis between TE and TL and various clinical indicators (***for P<0.001).
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