Impact of X/Y genes and sex hormones on mouse neuroanatomy

Dulcie A Vousden; Christina Corre; Shoshana Spring; Lily R Qiu; Ariane Metcalf; Elizabeth Cox; Jason P Lerch; Mark R Palmert

doi:10.1016/j.neuroimage.2018.02.051

Impact of X/Y genes and sex hormones on mouse neuroanatomy

Neuroimage. 2018 Jun:173:551-563. doi: 10.1016/j.neuroimage.2018.02.051. Epub 2018 Mar 2.

Authors

Dulcie A Vousden¹, Christina Corre², Shoshana Spring³, Lily R Qiu⁴, Ariane Metcalf³, Elizabeth Cox³, Jason P Lerch⁵, Mark R Palmert⁶

Affiliations

¹ Mouse Imaging Centre and Program in Neuroscience and Mental Health, The Hospital for Sick Children, 25 Orde Street, Toronto, ON, M5T 3H7, Canada; Department of Medical Biophysics, The University of Toronto, 101 College Street, Suite 15-701, Toronto, ON, M5G 1L7, Canada.
² Division of Endocrinology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.
³ Mouse Imaging Centre and Program in Neuroscience and Mental Health, The Hospital for Sick Children, 25 Orde Street, Toronto, ON, M5T 3H7, Canada.
⁴ Mouse Imaging Centre and Program in Neuroscience and Mental Health, The Hospital for Sick Children, 25 Orde Street, Toronto, ON, M5T 3H7, Canada; Institute of Medical Science, Faculty of Medicine, University of Toronto, Medical Sciences Building, 1 King's College Circle, Room 2374, Toronto, Ontario, M5S 1A8, Canada.
⁵ Mouse Imaging Centre and Program in Neuroscience and Mental Health, The Hospital for Sick Children, 25 Orde Street, Toronto, ON, M5T 3H7, Canada; Department of Medical Biophysics, The University of Toronto, 101 College Street, Suite 15-701, Toronto, ON, M5G 1L7, Canada. Electronic address: jason.lerch@sickkids.ca.
⁶ Division of Endocrinology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada; Institute of Medical Science, Faculty of Medicine, University of Toronto, Medical Sciences Building, 1 King's College Circle, Room 2374, Toronto, Ontario, M5S 1A8, Canada; Department of Paediatrics, The University of Toronto, 555 University Avenue, Toronto, Ontario, M5G 1X8, Canada; Department of Physiology, The University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada. Electronic address: mark.palmert@sickkids.ca.

PMID: 29501873
DOI: 10.1016/j.neuroimage.2018.02.051

Abstract

Biological sex influences brain anatomy across many species. Sex differences in brain anatomy have classically been attributed to differences in sex chromosome complement (XX versus XY) and/or in levels of gonadal sex steroids released from ovaries and testes. Using the four core genotype (4CG) mouse model in which gonadal sex and sex chromosome complement are decoupled, we previously found that sex hormones and chromosomes influence the volume of distinct brain regions. However, recent studies suggest there may be more complex interactions between hormones and chromosomes, and that circulating steroids can compensate for and/or mask underlying chromosomal effects. Moreover, the impact of pre vs post-pubertal sex hormone exposure on this sex hormone/sex chromosome interplay is not well understood. Thus, we used whole brain high-resolution ex-vivo MRI of intact and pre-pubertally gonadectomized 4CG mice to investigate two questions: 1) Do circulating steroids mask sex differences in brain anatomy driven by sex chromosome complement? And 2) What is the contribution of pre- versus post-pubertal hormones to sex-hormone-dependent differences in brain anatomy? We found evidence of both cooperative and compensatory interactions between sex chromosomes and sex hormones in several brain regions, but the interaction effects were of low magnitude. Additionally, most brain regions affected by sex hormones were sensitive to both pre- and post-pubertal hormones. This data provides further insight into the biological origins of sex differences in brain anatomy.

Keywords: Compensation; Four core genotypes; Mouse MRI; Sex chromosomes; Sex differences; Sex hormones.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain / anatomy & histology*
Female
Genotype
Gonadal Steroid Hormones*
Magnetic Resonance Imaging
Male
Mice
Mice, Mutant Strains
Sex Characteristics*
X Chromosome*
Y Chromosome*

Substances

Gonadal Steroid Hormones