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

Horm Behav. 2018 Apr;100:39-46. doi: 10.1016/j.yhbeh.2018.03.003. Epub 2018 Mar 12.


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.

Keywords: Brain; Motoneuron; Onuf's nucleus; Primate; Sex difference; Spinal cord; Testosterone.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Androgen Antagonists / pharmacology*
  • Androgens / pharmacology*
  • Animals
  • Animals, Newborn
  • Cell Count
  • Cell Size
  • Female
  • Macaca mulatta
  • Male
  • Motor Neurons / cytology
  • Motor Neurons / drug effects*
  • Motor Neurons / physiology
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / physiology
  • Pregnancy
  • Prenatal Exposure Delayed Effects* / chemically induced
  • Prenatal Exposure Delayed Effects* / psychology
  • Sex Characteristics*
  • Spinal Cord / cytology
  • Spinal Cord / drug effects*
  • Spinal Cord / physiology
  • Testosterone / pharmacology*


  • Androgen Antagonists
  • Androgens
  • Testosterone