Abnormal labyrinthine zone in the Hectd1 -null placenta

Abstract

Introduction The labyrinthine zone of the placenta is where exchange of nutrients and waste occurs between maternal and fetal circulations. Proper development of the placental labyrinth is essential for successful growth of the developing fetus and abnormalities in placental development are associated with intrauterine growth restriction (IUGR), preeclampsia and fetal demise. Our previous studies demonstrate that Hectd1 is essential for development of the junctional and labyrinthine zones of the placenta. Here we further characterize labyrinthine zone defects in the Hectd1 mutant placenta. Methods The structure of the mutant placenta was compared to wildtype littermates using histological methods. The expression of cell type specific markers was examined by immunohistochemistry and in situ hybridization. Results Hectd1 is expressed in the labyrinthine zone throughout development and the protein is enriched in syncytiotrophoblast layer type I cells (SynT-I) and Sinusoidal Trophoblast Giant cells (S-TGCs) in the mature placenta. Mutation of Hectd1 results in pale placentas with frequent hemorrhages along with gross abnormalities in the structure of the labyrinthine zone including a smaller overall volume and a poorly elaborated fetal vasculature that contain fewer fetal blood cells. Examination of molecular markers of labyrinthine trophoblast cell types reveals increased Dlx3 positive cells and Syna positive SynT-I cells, along with decreased Hand1 and Ctsq positive sinusoidal trophoblast giant cells (S-TGCs). Discussion Together these defects indicate that Hectd1 is required for development of the labyrinthine zone or the mouse placenta.

Mechanistic Insight into Long Noncoding RNAs and the Placenta

“…lncRHOFX1 is a newly-discovered 4.8-kb lncRNA located on the X chromosome and is one of the most abundantly expressed lncRNAs in the trophectoderm and primitive endoderm [ 107 ]. In addition, lncRHOFX1 is expressed highly within syncytio- and extravillous cytotrophoblast (EVTs) cells obtained by differentiating human embryonic stem cells (hESCs) in an in vitro culture model [ 108 , 109 , 110 ]. lncRHOFX1 is also expressed by JEG-3 cells and primary isolated EVTs.…”

Effect of Rhodomyrtus tomentosa Hassk. on HIF1α and VEGF expressions on hypertension placental

“…Damage to the labyrinth zone is strongly linked to intrauterine growth retardation (IUGR) (Belkacemi et al, 2011;Hemberger, 2012). Because of its high blood flow, high cellular proliferative activity, and long proliferative period compared to other parts of the placenta, the labyrinthine zone is vulnerable to target sites in placental free radicals (Sarkar et al, 2016). The basal zone, which forms just beneath the labyrinthine zone, is made up of spongiotrophoblasts, glycogen cells, and trophoblast giant cells (secondary).…”

Ubiquitin ligases: guardians of mammalian development

“…Extraembryonic silencing of CUL4B elevates levels of p21 and cyclin E, resulting in cell-cycle arrest, growth arrest, apoptosis of extraembryonic tissues, and embryonic lethality 48,104 . A similar outcome of intrauterine growth restriction and embryonic lethality occurs from dysregulated placental-HECTD1-mediated Hsp90 localization, CUL3-mediated cyclin E degradation, and MULE-mediated Mcl-1 and p53 degradation 47,[105][106][107] . In fact, altered MULE expression is characteristic of human pre-eclampsia and intrauterine growth restriction placentae 105 .…”