TY - JOUR
T1 - In vivo magnetic resonance imaging reveals the effect of gonadal hormones on morphological and functional brain sexual dimorphisms in adult sheep
AU - Barrière, David André
AU - Ella, Arsène
AU - Adriaensen, Hans
AU - Roselli, Charles E.
AU - Chemineau, Philippe
AU - Keller, Matthieu
N1 - Funding Information:
We thank Didier Chesneau and Chantal Porte for their valuable help at different stages of this project. We thank all the shepherds, especially Damien Capo, Olivier Lasserre and Didier Dubreuil, from the experimental unit (UEPAO) for the care provided to the animals. We are also grateful to Anne-Lyse Lainé, Corinne Laclie and Dominique Gennetay from the laboratoire de Phénotypage-Endocrinologie for hormonal assays. We thank all the staff from the CIRE platform for their help during surgeries and imaging sessions, especially Gilles Gomot, Christian Moussu and Frédéric Elleboudt. Finally, we thank Julie Bakker, Charlotte Cornil and Jacques Balthazart for helpful feedback on this manuscript. This project was funded by grants from the French Agence Nationale de la Recherche (ANR) and the regional council Centre-Val-de-Loire (Pherobouc project). Additional funding to CER provided by NIH R01 OD011047 .
Publisher Copyright:
© 2019 Elsevier Ltd
PY - 2019/11
Y1 - 2019/11
N2 - Sex differences in the brain and behavior are produced by the perinatal action of testosterone, which is converted into estradiol by the enzyme aromatase in the brain. Although magnetic resonance imaging (MRI) has been widely used in humans to study these differences, the use of animal models, where hormonal status can be properly manipulated, is necessary to explore the mechanisms involved. We used sheep, a recognized model in the field of neuroendocrinology, to assess brain morphological and functional sex differences and their regulation by adult gonadal hormones. To this end, we performed voxel-based morphometry and a resting-state functional MRI approach to assess sex differences in gonadally intact animals. We demonstrated significant sex differences in gray matter concentration (GMC) at the level of the gonadotropic axis, i.e., not only within the hypothalamus and pituitary but also within the hippocampus and the amygdala of intact animals. We then performed the same analysis one month after gonadectomy and found that some of these differences were reduced, especially in the hypothalamus and amygdala. By contrast, we found few differences in the organization of the functional connectome between males and females either before or after gonadectomy. As a whole, our study identifies brain regions that are sexually dimorphic in the sheep brain at the resolution of the MRI and highlights the role of gonadal hormones in the maintenance of these differences.
AB - Sex differences in the brain and behavior are produced by the perinatal action of testosterone, which is converted into estradiol by the enzyme aromatase in the brain. Although magnetic resonance imaging (MRI) has been widely used in humans to study these differences, the use of animal models, where hormonal status can be properly manipulated, is necessary to explore the mechanisms involved. We used sheep, a recognized model in the field of neuroendocrinology, to assess brain morphological and functional sex differences and their regulation by adult gonadal hormones. To this end, we performed voxel-based morphometry and a resting-state functional MRI approach to assess sex differences in gonadally intact animals. We demonstrated significant sex differences in gray matter concentration (GMC) at the level of the gonadotropic axis, i.e., not only within the hypothalamus and pituitary but also within the hippocampus and the amygdala of intact animals. We then performed the same analysis one month after gonadectomy and found that some of these differences were reduced, especially in the hypothalamus and amygdala. By contrast, we found few differences in the organization of the functional connectome between males and females either before or after gonadectomy. As a whole, our study identifies brain regions that are sexually dimorphic in the sheep brain at the resolution of the MRI and highlights the role of gonadal hormones in the maintenance of these differences.
KW - Gonadectomy
KW - Resting state fMRI
KW - Sex differences
KW - Sheep
KW - Voxel-based morphometry
UR - http://www.scopus.com/inward/record.url?scp=85071129707&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85071129707&partnerID=8YFLogxK
U2 - 10.1016/j.psyneuen.2019.104387
DO - 10.1016/j.psyneuen.2019.104387
M3 - Article
C2 - 31465941
AN - SCOPUS:85071129707
SN - 0306-4530
VL - 109
JO - Psychoneuroendocrinology
JF - Psychoneuroendocrinology
M1 - 104387
ER -