T Biron-Shental1, R Sukenik-Halevy2, H Naboani3, M Liberman4, R Kats4, A Amiel5. 1. Department of Obstetrics and Gynecology, Meir Medical Center, Kfar Saba, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: shentalt@inter.net.il.com. 2. Department of Obstetrics and Gynecology, Meir Medical Center, Kfar Saba, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; Genetic Institute, Meir Medical Center, Kfar Saba, Israel. 3. Department of Obstetrics and Gynecology, Meir Medical Center, Kfar Saba, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. 4. Genetic Institute, Meir Medical Center, Kfar Saba, Israel. 5. Genetic Institute, Meir Medical Center, Kfar Saba, Israel; Faculty of Life Sciences, Bar Ilan University, Ramat Gan, Israel.
Abstract
INTRODUCTION: The intrauterine environment, including the placenta, is influenced by a variety of factors, among which is diabetes during pregnancy. These factors can affect lifetime morbidity. Senescence is a state of cellular metabolic arrest, known to be correlated with age-related diseases and is usually accompanied by short telomeres. This study evaluated telomere characteristics in placentas and in cord blood from term pregnancies complicated by uncontrolled diabetes mellitus. METHODS: Placental biopsies and cord blood were collected from 16 pregnancies with poorly controlled diabetes and from 16 healthy controls. Senescence-associated heterochromatin foci (SAHF) and senescence-associated β-galactosidase (SAβ-Gal) staining were evaluated. Apoptosis was evaluated using tunel staining. Telomere length and aggregate formation were assessed in placentas and in cord blood using Q-FISH. RESULTS: Increased SAHF (19.28% ± 7.93 vs. 7.78% ± 5.31, P < 0.001) and SAβ-Gal (7.1% ± 1.32 vs. 0.8% ± 0.41, P < 0.001), but not apoptosis were present in placentas from diabetic pregnancies compared to controls. Higher percentage of trophoblasts with short telomeres (24.42% ± 12.6 vs. 4.92% ± 6.4, P = 0.013) and noticeably more aggregate formation (2.75% ± 1.14 vs. 0.62% ± 0.87, P < 0.001) were observed in diabetic placentas compared to controls. These differences were not observed in cord blood samples. DISCUSSION: Poorly controlled diabetes is related to increased senescence and shorter telomeres in placentas. Those findings may partially explain increased long-term, related morbidity.
INTRODUCTION: The intrauterine environment, including the placenta, is influenced by a variety of factors, among which is diabetes during pregnancy. These factors can affect lifetime morbidity. Senescence is a state of cellular metabolic arrest, known to be correlated with age-related diseases and is usually accompanied by short telomeres. This study evaluated telomere characteristics in placentas and in cord blood from term pregnancies complicated by uncontrolled diabetes mellitus. METHODS: Placental biopsies and cord blood were collected from 16 pregnancies with poorly controlled diabetes and from 16 healthy controls. Senescence-associated heterochromatin foci (SAHF) and senescence-associated β-galactosidase (SAβ-Gal) staining were evaluated. Apoptosis was evaluated using tunel staining. Telomere length and aggregate formation were assessed in placentas and in cord blood using Q-FISH. RESULTS: Increased SAHF (19.28% ± 7.93 vs. 7.78% ± 5.31, P < 0.001) and SAβ-Gal (7.1% ± 1.32 vs. 0.8% ± 0.41, P < 0.001), but not apoptosis were present in placentas from diabetic pregnancies compared to controls. Higher percentage of trophoblasts with short telomeres (24.42% ± 12.6 vs. 4.92% ± 6.4, P = 0.013) and noticeably more aggregate formation (2.75% ± 1.14 vs. 0.62% ± 0.87, P < 0.001) were observed in diabetic placentas compared to controls. These differences were not observed in cord blood samples. DISCUSSION: Poorly controlled diabetes is related to increased senescence and shorter telomeres in placentas. Those findings may partially explain increased long-term, related morbidity.
Authors: Line Hjort; Regan Vryer; Louise G Grunnet; David Burgner; Sjurdur F Olsen; Richard Saffery; Allan Vaag Journal: Diabetologia Date: 2018-01-23 Impact factor: 10.122
Authors: Christopher W Jones; Cecilia Gambala; Kyle C Esteves; Maeve Wallace; Reid Schlesinger; Marguerite O'Quinn; Laura Kidd; Katherine P Theall; Stacy S Drury Journal: Am J Obstet Gynecol Date: 2016-11-16 Impact factor: 8.661
Authors: Isabel Garcia-Martin; Richard J A Penketh; Anna B Janssen; Rhiannon E Jones; Julia Grimstead; Duncan M Baird; Rosalind M John Journal: PLoS One Date: 2018-12-11 Impact factor: 3.240
Authors: Dries S Martens; Michelle Plusquin; Wilfried Gyselaers; Immaculata De Vivo; Tim S Nawrot Journal: BMC Med Date: 2016-10-18 Impact factor: 8.775
Authors: Sonja Entringer; Karin de Punder; Claudia Buss; Pathik D Wadhwa Journal: Philos Trans R Soc Lond B Biol Sci Date: 2018-03-05 Impact factor: 6.237
Authors: Maria Tsamou; Dries S Martens; Bianca Cox; Narjes Madhloum; Karen Vrijens; Tim S Nawrot Journal: J Transl Med Date: 2018-09-12 Impact factor: 5.531
Authors: Diana B P Clemente; Lea Maitre; Mariona Bustamante; Leda Chatzi; Theano Roumeliotaki; Serena Fossati; Regina Grazuleviciene; Kristine B Gützkow; Johanna Lepeule; Dries S Martens; Rosie R C McEachan; Helle M Meltzer; Inga Petraviciene; Rémy Slama; Ibon Tamayo-Uria; Jose Urquiza; Marina Vafeiadi; John Wright; Tim S Nawrot; Martine Vrijheid Journal: Sci Rep Date: 2019-12-10 Impact factor: 4.379