Placental telomere shortening in stillbirth: a sign of premature senescence?

The objective of this study is to investigate placental telomere shortening in unexplained stillbirths (SBs) as an indication of premature senescence.Placentas were collected from 42 unexplained SB (22 weeks), 43 term and 15 preterm live births, at the Policlinico Hospital of Modena (Italy). DNA extracted from placentae was studied for telomere length by real time PCR. Standard curves were generated for telomere lengths from single copy gene amplifications using a reference DNA. The telomere length for each sample was derived based on the ratio of telomere length between the sample and single copy gene standard (T/S ratio). The mean ratio of placental telomere in term live births was 5.181 ± 3.841.A twofold decrease in telomere length was seen in SBs (over all 2.455 ± 1.239; p0.001). For early SBs (above 34 weeks), the T/S was 2.8884 ± 1.224 and for late SBs, the T/S was 2.207 ± 1.201, both lower than term live births (both p0.01). T/S remained lower both in small for gestational age-SB (2.639 ± 1.619) and appropriate for gestational age-SB (2.653 ± 1.335) with no difference between these subgroups (p = ns). T/S was lower in SB compared with spontaneous preterm births (PTBs) (6.382 ± 5.525; p0.01), whereas SBs telomere length were similar to those of preterm premature rupture of membranes (pPROM) (3.296 ± 3.599; p = ns).Substantial reduction in telomere length in SBs is indicative of placental senescence. These data provide mechanistic insights that premature aging may lead to placental dysfunction as an initiator of fetal demise in unexplained SBs.