Telomeres, oxidative stress, and timing for spontaneous term and preterm labor

Abstract

Telomeres are nucleoprotein complexes located at the distal ends of chromosomes. In adults, progressive telomere shortening occurs throughout the lifetime and is thought to contribute to progressive aging, physiological senescence, multiorgan dysfunction, and ultimately, death. As discussed in this review, multiple lines of evidence provide support for the biological plausibility that a telomere-based clock mechanism also determines the length of gestation, leading to the onset of labor (parturition). After telomere expansion at the beginning of pregnancy, the telomere lengths in the gestational tissues (ie, the placenta and fetal membranes) progressively shorten throughout the remainder of pregnancy. The rate of telomere shortening can be accelerated by conditions that affect the mother and result in oxidative stress. Preterm births in the United States are associated with multiple risk factors that are linked with increased oxidative stress. Antioxidant vitamins (ie, vitamins E and C) mitigate the effects of oxidative stress and delay or prevent telomere shortening. Clinical trials with vitamins E and C and with multivitamins started during the periconception period have been associated with reduced rates of preterm births. In the United States, African-American women have a 2-3-fold higher rate of preterm birth. African-American women have multiple risk factors for premature birth, all of which are distinct and potentially additive with regard to epigenetic telomere shortening. The "weathering effect" is the hypothesis to explain the increased rates of chronic illness, disabilities, and early death observed in African-Americans. With regard to pregnancy, accelerated weathering with the associated telomere shortening in the gestational tissues would not only explain the preterm birth disparity but could also explain why highly educated, affluent African-American women continue to have an increased rate of preterm birth. These studies suggest that the racial disparities in preterm birth are potentially mediated by telomere shortening produced by lifetime or even generational exposure to the effects of systemic racism and socioeconomic marginalization. In conclusion, this review presents multiple lines of evidence supporting a novel hypothesis regarding the biological clock mechanism that determines the length of pregnancy, and it opens the possibility of new approaches to prevent or reduce the rate of spontaneous preterm birth.

Keywords: antioxidants; apoptosis; biological clock; cell-free DNA; gestational length; nativity effect; preterm birth; racial disparity; telomere shortening; vitamin C; vitamin E; weathering.