Differences in placental telomere length suggest a link between racial disparities in birth outcomes and cellular aging

Abstract

BACKGROUND Health disparities begin early in life and persist across the life course. Despite current efforts Black women exhibit greater risk for pregnancy complications and negative perinatal outcomes compared to White women. The placenta, a complex multi-tissue organ, serves as the primary transducer of bidirectional information between the mother and fetus. Altered placental function is linked to multiple racially disparate pregnancy complications, however little is known about racial differences in molecular factors within the placenta. Several pregnancy complications, including preeclampsia and fetal growth restriction, exhibit racial disparities and are associated with shorter placental telomere length, an indicator of cellular stress and aging. Cellular senescence and telomere dynamics are linked to the molecular mechanisms associated with the onset of labor and parturition. Further, racial differences in telomere length are found in a range of different peripheral tissues. Together these factors suggest that exploration of racial differences in telomere length of the placenta may provide novel mechanistic insight into racial disparities in birth outcomes. OBJECTIVE This study examined whether telomere length measured in four distinct fetally-derived tissues were significantly different between Blacks and Whites. The study had two hypotheses: (1) that telomere length measured in different placental tissue types would be correlated and (2) that across all sampled tissues telomere length would differ by race. STUDY DESIGN In a prospective study, placental tissue samples were collected from the amnion, chorion, villus, and umbilical cord from Black and White singleton pregnancies (N=46). Telomere length was determined using monochrome multiplex quantitative real-time polymerase chain reaction in each placental tissue. Demographic and pregnancy-related data were also collected. Descriptive statistics characterized the sample overall and among Black and White women separately. The overall impact of race was assessed by multilevel mixed-effects linear regression models that included empirically relevant covariates. RESULTS Telomere length was significantly correlated across all placental tissues. Pairwise analyses of placental tissue telomere length revealed significantly longer telomere length in the amnion compared to the chorion (t=−2.06, p=0.043). Overall telomere length measured in placenta samples from Black mothers were significantly shorter than those from White mothers (β=−0.09, p=0.04). Controlling for relevant maternal and infant characteristics strengthened the significance of the observed racial differences (β=−0.12, p=0.02). Within tissue analyses revealed that the greatest difference by race was found in chorionic telomere length (t=−2.81, p=0.007). CONCLUSION These findings provide the first evidence of racial differences in placental telomere length. Telomere length was significantly shorter in placental samples derived from Black mothers compared to White. Given previous studies repo...

Preterm labor in the absence of acute histologic chorioamnionitis is characterized by cellular senescence of the chorioamniotic membranes

“…One mechanism capable of elongating telomeres includes the ectopic expression of the enzyme telomerase, which lessens telomere shortening generated during cell division and evades cellular senescence 101 . Upon exposure to mild oxidative stress, cells reduce their replicative capacity and exhibit telomere shortening, which is thought to represent cellular senescence 102–113 . Telomere shortening has been observed in the chorioamniotic membranes from women who underwent spontaneous labor at term 35 and in those from women who underwent spontaneous preterm labor with pPROM 114 .…”

Contribution of Socioeconomic Status to Racial/Ethnic Disparities in Adverse Pregnancy Outcomes Among Women With Systemic Lupus Erythematosus

“…Despite the small sample sizes for minority women, the 3‐fold higher odds of APO in whites and 6‐fold higher odds in African Americans remained significant after adjustment of SES. These results suggest that the association of race/ethnicity in this group is explained by other factors, such as genetics, increased stress levels, and shorter placental telomere length .…”

Sex-specific associations between telomere length and candidate miRNA expression in placenta

“…In addition, placental telomere length has been previously associated with in utero environmental exposures such as pre-pregnancy BMI [ 9 ], air pollution [ 17 ] and tobacco smoking [ 58 ]. Newborn’s sex, paternal age [ 9 ], parity, gestational age [ 59 ] and race [ 60 ] were also shown to affect the placental telomere length.…”

“…In a first sensitivity analysis ( Model 1 ), we tested whether the ethnicity of the newborn affected these associations between placental miRNAs and telomere length, as racial differences in placental telomere length have been previously demonstrated [ 60 ]. The newborns with non-European origin were excluded from the analysis, resulting in a subpopulation consisting of 98 and 88 newborn girls and boys, respectively.…”