Abstract
16p11.2 Microdeletion Induces Sex-Specific Defects in Placental Development in Mice
Placenta (Eastbourne), Vol.154, pp.e16-e17
09/02/2024
DOI: 10.1016/j.placenta.2024.07.101
Abstract
Objectives: Neurodevelopmental disorders (NDDs) are extremely common. The prenatal environment significantly influences NDD risk which may include how NDD risk genes affect placental function. However, placental disruptions in mouse models of NDD risk genes remain unexplored. Our objective was to investigate placental development and function in the 16p11.2 microdeletion model (16p del). 16p del in humans is associated with NDDs including autism spectrum disorder, attention deficit hyperactivity disorder, and intellectual disability. Mice modeling this deletion display sex-specific behavioral phenotypes relevant to NDDs, mirroring the male bias observed in human NDDs. We hypothesized that 16p del would alter placental growth and function with more severe phenotypes observed in male placentas.
Methods: To test this, wildtype female mice were bred with hemizygous 16p del males, and placental weight, fetal weight, placental morphology, and placental gene expression were assessed.
Results: Male 16p del placental mass was increased at embryonic day 16 (E16) and E18 compared to litter-matched wildtypes; females showed no group differences. This increased 16p del male placental weight may have been related to increased E16 decidual proportion we found in 16p del males, a phenotype typically associated with reduced fetal growth. Indeed, both male and female 16p del embryos had reduced body weight at E14 and E16, but females recovered body weight to wildtype levels on E18. There were no group differences in E16 female placental subregion morphology. Unexpectedly, E16 16p del male placentas exhibited comparable expression to wildtypes in two of three 16p11.2 genes tested. E16 16p del female placentas, on the other hand, showed the expected 50% expression level in all three genes. E16 16p del male placentas also had increased expression of growth factors Igf-1 and Vegf.
Conclusion: The sex-specific placental abnormalities in 16p del mice likely impact postnatal development and may contribute to early developmental origins of male bias in NDDs.
Details
- Title: Subtitle
- 16p11.2 Microdeletion Induces Sex-Specific Defects in Placental Development in Mice
- Creators
- Annemarie Carver - University of IowaBenjamin Kelvingtion - Iowa Neuroscience Institute, Carver College of Medicine, University of Iowa, Iowa City, USAFaith Fairbairn - Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, USATed Abel - University of IowaHanna Stevens - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Placenta (Eastbourne), Vol.154, pp.e16-e17
- Publisher
- Elsevier Ltd
- DOI
- 10.1016/j.placenta.2024.07.101
- ISSN
- 0143-4004
- Language
- English
- Date published
- 09/02/2024
- Academic Unit
- Molecular Physiology and Biophysics; Psychiatry; Neuroscience and Pharmacology; Psychological and Brain Sciences; Biochemistry and Molecular Biology; Iowa Neuroscience Institute
- Record Identifier
- 9984699518902771
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