title: Mid- to late term hypoxia in the mouse alters placental morphology, glucocorticoid regulatory pathways and nutrient transporters in a sex-specific manner.
abstract: Maternal hypoxia is a common perturbation that can disrupt placental and thus fetal development, contributing to neonatal impairments. Recently, evidence has suggested that physiological outcomes are dependent upon the sex of the fetus, with males more susceptible to hypoxic insults than females. This study investigated the effects of maternal hypoxia during mid- to late gestation on fetal growth and placental development and determined if responses were sex specific. CD1 mice were housed under 21% or 12% oxygen from embryonic day (E) 14.5 until tissue collection at E18.5. Fetuses and placentas were weighed before collection for gene and protein expression and morphological analysis. Hypoxia reduced fetal weight in both sexes at E18.5 by 7% but did not affect placental weight. Hypoxia reduced placental mRNA levels of the mineralocorticoid and glucocorticoid receptors and reduced the gene and protein expression of the glucocorticoid metabolizing enzyme HSD11B2. However, placentas of female fetuses responded differently to maternal hypoxia than did placentas of male fetuses. Notably, morphology was significantly altered in placentas from hypoxic female fetuses, with a reduction in placental labyrinth blood spaces. In addition mRNA expression of Glut1, Igf2 and Igf1r were reduced in placentas of female fetuses only. In summary, maternal hypoxia altered placental formation in a sex specific manner through mechanisms involving placental vascular development, growth factor and nutrient transporter expression and placental glucocorticoid signalling. This study provides insight into how sex differences in offspring disease development may be due to sex specific placental adaptations to maternal insults.
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland, Australia.
authors.forename: J S M
authors.initials: JS
authors.lastname: Cuffe
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland, Australia.
authors.forename: S L
authors.initials: SL
authors.lastname: Walton
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland, Australia.
authors.forename: R R
authors.initials: RR
authors.lastname: Singh
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland, Australia.
authors.forename: J G
authors.initials: JG
authors.lastname: Spiers
authors.affiliation: School of Veterinary Science, The University of Queensland, Gatton, Queensland, Australia.
authors.forename: H
authors.initials: H
authors.lastname: Bielefeldt-Ohmann
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland, Australia.
authors.forename: L
authors.initials: L
authors.lastname: Wilkinson
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland, Australia.
authors.forename: M H
authors.initials: MH
authors.lastname: Little
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland, Australia k.moritz@uq.edu.au.
authors.forename: K M
authors.initials: KM
authors.lastname: Moritz
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics / Q000378:metabolism; D026924:Amino Acid Transport System A / Q000235:genetics; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003345:Corticosterone / Q000097:blood; D005260:Female; D051272:Glucose Transporter Type 1 / Q000235:genetics; D000860:Hypoxia / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D008297:Male; D051379:Mice; D010920:Placenta / Q000378:metabolism*; D010929:Placentation; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics; D012727:Sex Characteristics
chemical_list: D026924:Amino Acid Transport System A; D001786:Blood Glucose; D051272:Glucose Transporter Type 1; C513121:IGF2 protein, mouse; D012333:RNA, Messenger; C495678:Slc2a1 protein, mouse; C432411:Slc38a1 protein, mouse; D007335:Insulin-Like Growth Factor II; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D017526:Receptor, IGF Type 1; D003345:Corticosterone