Placental telomere length shortening is not associated with severe preeclampsia but the gestational age

Abstract

Variations in telomere length (TL) have been associated with aging, stress, and many diseases. Placenta TL is an essential molecular component influencing the outcome of birth. Previous investigations into the relationship between placenta TL and preeclampsia (PE) have produced conflicting findings. We conducted a retrospective case-control analysis in this study to address the disparity. We used placenta samples from 224 births received from Hawaii Biorepository (HiBR) between 2006 and 2013, comprising 129 healthy full-term controls and 95 severe PE samples. The average absolute placental TL was calculated using the quantitative polymerase chain reaction (qPCR) technique. We utilized multiple linear regressions to associate placental TL with severe PE and other demographic, clinical and physiological data. The outcome demonstrates that the placental TL of severe PE cases did not significantly differ from that of healthy controls. Instead, there is a strong correlation between gestational age and placenta TL shortening. Placental TL also exhibits racial differences: (1) Latino moms' TL is significantly longer than non-Latino mothers' (p=0.009). (2) Caucasian patients with severe PE have shorter TL than non-Caucasian patients (p=0.0037). This work puts the long-standing question of whether severe PE influences placental TL to rest. Placental TL is not related to severe PE but is negatively associated with gestational age and is also affected by race.

Keywords: placenta; placenta aging; preeclampsia; pregnancy; telomere length.

Figure 1

The lack of association between severe preeclampsia (PE) and telomere length (TL) after stratifying by gestational age. (A) Distribution of ln-transformed relative placental TL in the third trimester. Red color: severe PE samples; Blue color: control samples. (B) Severe PE is highly confounded by clinical variables. Top 10 most relevant phenotypic variables of severe PE, calculated using logistic regression. (C) Top 10 variables with the highest proportion of variance explained (PVE), per ANOVA analysis. (D) Scatter plot of TL by delivery gestational age, with red dots representing severe PE cases and blue dots representing controls. The black line represents linear regression of TL on gestational age using all samples; the red line shows the linear regression of TL on gestational age using only severe PE cases. (E) Boxplots of placenta TL of term severe PE samples (n=18) and term controls (n=133). (F) Boxplots of placenta TL of term severe PE samples (n=18) and the subset of matched term controls (n=18) stratified by gestational age (38, 39, 40+ weeks).

Figure 2

The associations between placental telomere length (TL) and race. Shown are the boxplot of placental TLs in Latino, Caucasian, African American, Pacific Islander and Asians in: (A) all samples (n=224); (B) severe PE samples (n=95); (C) control samples (n=129). “**” denotes the t-test p-value is less than 0.01, “*” denotes the t-test p-value less than 0.05 and “NS” means the p-value greater or equal to 0.05.