Effects of sex and prenatal androgen manipulations on Onuf's nucleus of rhesus macaques

• Type of Material: Article
• Authors: Nancy G. Forger, Georgia State University; Elara Ruszkowski, Georgia State University; Andrew Jacobs, Georgia State University; Kim Wallen, Emory University
• Language: English
• Date: 2018-04-01
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.yhbeh.2018.03.003
• Title of Journal or Parent Work: Hormones and Behavior
• ISSN: 0018-506X
• Volume: 100
• Start Page: 39
• End Page: 46
• Grant/Funding Information: This study was partially supported by the National Center for Research Resources P51RR165 and is currently supported by the Office of Research Infrastructure Programs/OD/P51OD11132.; Further support was in part by NIH Grants R01-MH50268 to K.W.
• Keywords: Cell Count; Spinal cord; Brain; Primate; Androgen Antagonists; Muscle, Skeletal; Macaca mulatta; Testosterone; Cell Size; Female; Prenatal Exposure Delayed Effects; Male; Spinal Cord; Sex Characteristics; Onuf's nucleus; Animals, Newborn; Sex difference; Androgens; Motor Neurons; Pregnancy; Motoneuron; Animals
• Research Categories: Psychology, Physiological; Biology, Neuroscience

Abstract

The role of gonadal steroids in sexual differentiation of the central nervous system (CNS) is well established in rodents, but no study to date has manipulated androgens prenatally and examined their effects on any CNS structure in a primate. Onuf's nucleus is a column of motoneurons in the sacral spinal cord that innervates the striated perineal muscles. This cell group is larger in males than in females of many species, due to androgens acting during a sensitive perinatal period. Here, we examined Onuf's nucleus in 21 adult rhesus monkeys, including control males and females, as well as males whose mothers had been treated with an anti-androgen or testosterone during gestation. We found a robust sex difference, with more motoneurons in control males than in females. The soma size of Onuf's nucleus motoneurons was also marginally larger in males. Treatment with the anti-androgen flutamide for 35–40 days during early gestation partially blocked masculinization of Onuf's nucleus: motoneuron number in flutamide-treated males was decreased relative to control and testosterone-treated males, but remained greater than in females, with no effect on cell size. A control motor nucleus that innervates foot muscles (Pes9) showed no difference in motoneuron number or size between control males and females. Prenatal testosterone treatment of males did not alter Onuf's nucleus motoneuron number, but did increase the size of both Onuf's and Pes9 motoneurons. Thus, prenatal androgen manipulations cause cellular-level changes in the primate CNS, which may underlie previously observed effects of these manipulations on behavior.