Katherine Leavey1, Samantha J Benton2, David Grynspan3, Shannon A Bainbridge4, Eric K Morgen5, Brian J Cox6. 1. Department of Physiology, University of Toronto, Ontario, Canada. 2. Department of Cellular and Molecular Medicine, University of Ottawa, Ontario, Canada. 3. Department of Pathology and Laboratory Medicine, University of Ottawa, Ontario, Canada. 4. Department of Cellular and Molecular Medicine, University of Ottawa, Ontario, Canada; Interdisciplinary School of Health Sciences, University of Ottawa, Ontario, Canada. 5. Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada. Electronic address: eric.morgen@utoronto.ca. 6. Department of Physiology, University of Toronto, Ontario, Canada; Department of Obstetrics and Gynaecology, University of Toronto, Ontario, Canada. Electronic address: b.cox@utoronto.ca.
Abstract
INTRODUCTION: The placenta demonstrates a recognized sequence of histomorphologic maturation throughout pregnancy, and in some cases, shows abnormally advanced (AVM) or delayed (DVM) villous maturation. While AVM and DVM have important clinical implications, it is unknown whether they truly represent a state of accelerated/delayed normal maturation or a state of pathological maldevelopment. The purpose of our study is, therefore, to address this challenge via a genome-wide search for expression markers of normal villous maturation (NM) and the assessment of these genes in cases of maturational pathology. METHODS: A total of 142 placentas, previously evaluated by gene expression microarray, were reviewed histologically and classified as NM, AVM, or DVM. Expression data from healthy NM placentas underwent Pearson correlations with gestational age (GA) and network/pathway analysis to identify candidate gene markers. Candidates were then validated in an independent microarray dataset and used to calculate "molecular GAs" of placentas with maturational pathology. RESULTS: Analysis of NM placentas yielded 17 candidate markers of normal villous maturation, of which 11 were independently validated. Genes with expression increasing across gestation were associated with transcription and metabolism, while those demonstrating decreasing expression were involved in cell cycle and division. Molecular GA was 5.3 weeks older than true GA among AVM placentas (p < 0.001), and 1.1 weeks younger among DVM placentas (p = 0.149). DISCUSSION: We have found evidence of advanced molecular GA in AVM placentas, while molecular alterations in DVM placentas were merely suggestive of delayed maturation. In the future, these findings will need to be validated with additional techniques such as in situ hybridization or immunohistochemistry.
INTRODUCTION: The placenta demonstrates a recognized sequence of histomorphologic maturation throughout pregnancy, and in some cases, shows abnormally advanced (AVM) or delayed (DVM) villous maturation. While AVM and DVM have important clinical implications, it is unknown whether they truly represent a state of accelerated/delayed normal maturation or a state of pathological maldevelopment. The purpose of our study is, therefore, to address this challenge via a genome-wide search for expression markers of normal villous maturation (NM) and the assessment of these genes in cases of maturational pathology. METHODS: A total of 142 placentas, previously evaluated by gene expression microarray, were reviewed histologically and classified as NM, AVM, or DVM. Expression data from healthy NM placentas underwent Pearson correlations with gestational age (GA) and network/pathway analysis to identify candidate gene markers. Candidates were then validated in an independent microarray dataset and used to calculate "molecular GAs" of placentas with maturational pathology. RESULTS: Analysis of NM placentas yielded 17 candidate markers of normal villous maturation, of which 11 were independently validated. Genes with expression increasing across gestation were associated with transcription and metabolism, while those demonstrating decreasing expression were involved in cell cycle and division. Molecular GA was 5.3 weeks older than true GA among AVM placentas (p < 0.001), and 1.1 weeks younger among DVM placentas (p = 0.149). DISCUSSION: We have found evidence of advanced molecular GA in AVM placentas, while molecular alterations in DVM placentas were merely suggestive of delayed maturation. In the future, these findings will need to be validated with additional techniques such as in situ hybridization or immunohistochemistry.
Authors: Theresa L Barke; Jeffery A Goldstein; Alexandra C Sundermann; Arun P Reddy; Jodell E Linder; Hernan Correa; Digna R Velez-Edwards; David M Aronoff Journal: Am J Reprod Immunol Date: 2018-07-09 Impact factor: 3.886
Authors: Yunsung Lee; Sanaa Choufani; Rosanna Weksberg; Samantha L Wilson; Victor Yuan; Amber Burt; Carmen Marsit; Ake T Lu; Beate Ritz; Jon Bohlin; Håkon K Gjessing; Jennifer R Harris; Per Magnus; Alexandra M Binder; Wendy P Robinson; Astanand Jugessur; Steve Horvath Journal: Aging (Albany NY) Date: 2019-06-24 Impact factor: 5.682