Parental Genetics Communicate with Intrauterine Environment to Reprogram Newborn Telomeres and Immunity

Abstract

Telomeres, markers for cellular senescence, have been found substantially influenced by parental inheritance. It is well known that genomic stability is preserved by the DNA repair mechanism through telomerase. This study aimed to determine the association between parents−newborn telomere length (TL) and telomerase gene (TERT), highlighting DNA repair combined with TL/TERT polymorphism and immunosenescence of the triad. The mother−father−newborn triad blood samples (n = 312) were collected from Ziauddin Hospitals, Pakistan, between September 2021 and June 2022. The telomere length (T/S ratio) was quantified by qPCR, polymorphism was identified by Sanger sequencing, and immunosenescence by flow cytometry. The linear regression was applied to TL and gene association. The newborns had longest TL (2.51 ± 2.87) and strong positive association (R = 0.25, p ≤ 0.0001) (transgenerational health effects) with mothers’ TL (1.6 ± 2.00). Maternal demographics—socioeconomic status, education, and occupation—showed significant effects on TL of newborns (p < 0.015, 0.034, 0.04, respectively). The TERT risk genotype CC (rs2736100) was predominant in the triad (0.6, 0.5, 0.65, respectively) with a strong positive association with newborn TL (β = 2.91, <0.0011). Further analysis highlighted the expression of KLRG 1+ in T-cells with shorter TL but less frequent among newborns. The study concludes that TERT, parental TL, antenatal maternal health, and immunity have a significantly positive effect on the repair of newborn TL.

Keywords: DNA repair; TERT; immunity; polymorphism; reprogramming; telomerase; telomere; telomere length (TL).

Figure 1

Telomere length (T/S ratio) comparison between mother, father and newborn. Newborn TL was longer, followed by mother and father TL.

Figure 2

(A,B) Comparison of mother age with newborn telomere length. The longest newborn telomere length (TL) was seen in mothers aged 21–25, whereas TL in mothers decreases with an increase in their age. (C,D) Comparison of fathers’ age with newborn telomere length. An increase in fathers’ age showed an increase in newborns TL. The longest father TL was seen in ages 21–25. (*) symbol for p < 0.05; (**) for p < 0.01; (***) for p < 0.001.

Figure 3

Telomere length (TL) comparison between newborn girls and boys. Girls have longer TL than boys.

Figure 4

(A–C) Association between newborn telomere length (TL) and gestational age and birth weight. There was no association between newborn weight and gestational age, but there was a positive association between gestational age and newborn weight.

Figure 5

(A,B) Linear regression between mother and father TL among genders. No association was found between girls and boys with both parents.

Figure 6

Sanger sequencing of TERT gene. Heterozygous genotype (AC) in both mothers and newborns but homozygous (AA, CC) in the father and newborns. The black arrow shows the SNP C/A allele at the restriction site rs2736100.

Figure 7

Comparison of immune markers (CD57, KLRG1) among mother, father, and newborn.

Figure 8

Comparison between telomere length and immune markers (CD57, KLRG1) in the triad: significant results (* p < 0.05) among mothers and newborns, whereas insignificant (p > 0.05) results between fathers and newborns. ns: not significant.