title: Pregnancy and estrogen enhance neural progenitor-cell proliferation in the vomeronasal sensory epithelium.
abstract: BACKGROUND
  The hormonal state during the estrus cycle or pregnancy produces alterations on female olfactory perception that are accompanied by specific maternal behaviors, but it is unclear how sex hormones act on the olfactory system to enable these sensory changes.
  
  
  RESULTS
  Herein, we show that the production of neuronal progenitors is stimulated in the vomeronasal organ (VNO) epithelium of female mice during a late phase of pregnancy. Using a wide range of molecular markers that cover the whole VNO cell maturation process in combination with Ca(2+) imaging in early postmitotic neurons, we show that newly generated VNO cells adopt morphological and functional properties of mature sensory neurons. A fraction of these newly generated cells project their axons to the olfactory forebrain, extend dendrites that contact the VNO lumen, and can detect peptides and urinary proteins shown to contain pheromone activity. High-throughput RNA-sequencing reveals concomitant differences in gene expression in the VNO transcriptomes of pregnant females. These include relative increases in expression of 20 vomeronasal receptors, of which 17 belong to the V1R subfamily, and may therefore be considered as candidate receptors for mediating maternal behaviors. We identify the expression of several hormone receptors in the VNO of which estrogen receptor α (Esr1) is directly localized to neural progenitors. Administration of sustained high levels of estrogen, but not progesterone, is sufficient to stimulate vomeronasal progenitor cell proliferation in the VNO epithelium.
  
  
  CONCLUSIONS
  Peripheral olfactory neurogenesis driven by estrogen may contribute to modulate sensory perception and adaptive VNO-dependent behaviors during pregnancy and early motherhood.
authors.affiliation: Department of Physiology, and Center for Integrative Physiology and Molecular Medicine, University of Saarland School of Medicine, 66421, Homburg, Germany. livio.oboti@gmail.com.|Present address: Center for Neuroscience Research, Children's National Health System, 20010, Washington, DC, USA. livio.oboti@gmail.com.
authors.forename: Livio
authors.initials: L
authors.lastname: Oboti
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK. xs1@sanger.ac.uk.
authors.forename: Ximena
authors.initials: X
authors.lastname: Ibarra-Soria
authors.affiliation: Department of Physiology, and Center for Integrative Physiology and Molecular Medicine, University of Saarland School of Medicine, 66421, Homburg, Germany. anabelpgo@gmail.com.
authors.forename: Anabel
authors.initials: A
authors.lastname: Pérez-Gómez
authors.affiliation: Department of Physiology, and Center for Integrative Physiology and Molecular Medicine, University of Saarland School of Medicine, 66421, Homburg, Germany. andreas.schmid@uks.eu.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schmid
authors.affiliation: Department of Physiology, and Center for Integrative Physiology and Molecular Medicine, University of Saarland School of Medicine, 66421, Homburg, Germany. martina.pyrski@uks.eu.
authors.forename: Martina
authors.initials: M
authors.lastname: Pyrski
authors.affiliation: Department of Physiology, and Center for Integrative Physiology and Molecular Medicine, University of Saarland School of Medicine, 66421, Homburg, Germany. n.paschek@gmx.de.
authors.forename: Nicole
authors.initials: N
authors.lastname: Paschek
authors.affiliation: Department of Physiology, and Center for Integrative Physiology and Molecular Medicine, University of Saarland School of Medicine, 66421, Homburg, Germany. sarah.kircher@uks.de.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kircher
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK. dl5@sanger.ac.uk.|Monell Chemical Senses Center, 3500 Market Street, Philadelphia, Pennsylvania, 19104, USA. dl5@sanger.ac.uk.
authors.forename: Darren W
authors.initials: DW
authors.lastname: Logan
authors.affiliation: Department of Physiology, and Center for Integrative Physiology and Molecular Medicine, University of Saarland School of Medicine, 66421, Homburg, Germany. trese.leinders@uks.de.
authors.forename: Trese
authors.initials: T
authors.lastname: Leinders-Zufall
authors.affiliation: Department of Physiology, and Center for Integrative Physiology and Molecular Medicine, University of Saarland School of Medicine, 66421, Homburg, Germany. frank.zufall@uks.eu.
authors.forename: Frank
authors.initials: F
authors.lastname: Zufall
authors.affiliation: Department of Physiology, and Center for Integrative Physiology and Molecular Medicine, University of Saarland School of Medicine, 66421, Homburg, Germany. pablo.chamero@uks.eu.|Present address: Laboratoire de Physiologie de la Reproduction & des Comportments, UMR 7247 INRA-CNRS-Université François Rabelais, F-37380, Nouzilly, France. pablo.chamero@uks.eu.
authors.forename: Pablo
authors.initials: P
authors.lastname: Chamero
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D051379:Mice; D058953:Neural Stem Cells / Q000502:physiology; D055495:Neurogenesis; D011247:Pregnancy; D019147:Vomeronasal Organ / Q000254:growth & development / Q000502:physiology*
chemical_list: D047628:Estrogen Receptor alpha; D004967:Estrogens