title: Sex-specific development of spatial orientation is independent of peripubertal gonadal steroids.
abstract: Prenatal exposure to androgens has been shown to modulate brain development, resulting in changed behavioral attitudes, sexual orientation and cognitive functions, including processing of spatial information. Whether later changes in gonadotropic hormones during puberty induce further organizational effects within the brain is still insufficiently understood. The purpose of this study was to assess development of spatial orientation before and after the time of normal pubertal development, in an ovine model where half of the animals did not undergo typical reproductive maturation due to the pharmacological blockade of gonadotropin releasing hormone receptor (GnRHR) signaling. The study formed part of a larger trial and utilized 46 pairs of same sex Scottish Mule Texel Cross twins (22 female and 24 male). One twin remained untreated throughout (control) while the other received a subcutaneous GnRH agonist (GnRHa: Goserelin-Acetate) implant every fourth week. GnRHa treatment began at eight and 28 weeks of age, in males and females respectively, because the timing of the pubertal transition is sexually differentiated in sheep as it is in humans. Spatial orientation was assessed at three different time points: eight weeks of age, before puberty and treatment in both sexes; 28 weeks of age, after 20 weeks GnRHa treatment in males and before puberty and GnRHa treatment in females; and at 48 weeks of age, which is after the normal time of the pubertal transition in both sexes. Spatial orientation was tested in a spatial maze with traverse time as the main outcome measure. GnRHa treatment did not affect spatial maze performance as no significant differences in traverse time between treated and untreated animals were observed at any time-point. Adolescent females (48 weeks of age) traversed the maze significantly faster than adolescent males, whereas no sex differences in traverse time were seen at earlier developmental stages (eight and 28 weeks). Development of sex differences in spatial orientation was independent of exposure to pubertal hormones since puberty-blocked and control animals both showed the same pattern of spatial maze performance. This result demonstrates the prenatal nature of spatial orientation development. Furthermore, the unexpected finding that female animals outperformed males in the spatial orientation task, underscores the importance of the testing context in spatial orientation experiments.
authors.affiliation: Department of Neuropsychiatry and Psychosomatic Medicine, Division of Surgery and Clinical Neuroscience, Oslo University Hospital - Rikshospitalet, 0027 Oslo, Norway; Faculty of Health Sciences, Oslo and Akershus University College of Applied Sciences, Pb 4 St. Olavsplass, 0130 Oslo, Norway.
authors.forename: Slawomir
authors.initials: S
authors.lastname: Wojniusz
authors.forename: Erik
authors.initials: E
authors.lastname: Ropstad
authors.forename: Neil
authors.initials: N
authors.lastname: Evans
authors.forename: Jane
authors.initials: J
authors.lastname: Robinson
authors.forename: Anne-Kristin
authors.initials: AK
authors.lastname: Solbakk
authors.forename: Tor
authors.initials: T
authors.lastname: Endestad
authors.forename: Ira Ronit Hebold
authors.initials: IR
authors.lastname: Haraldsen
mesh_terms: D000818:Animals; D004343:Drug Implants; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D017273:Goserelin / Q000008:administration & dosage / Q000494:pharmacology*; D008098:Litter Size; D008297:Male; D018782:Maze Learning / Q000502:physiology; D009949:Orientation / Q000502:physiology*; D010053:Ovary / Q000254:growth & development / Q000378:metabolism*; D011897:Random Allocation; D012727:Sex Characteristics; D012741:Sexual Maturation / Q000502:physiology*; D012756:Sheep; D013028:Space Perception / Q000502:physiology*; D013045:Species Specificity; D013737:Testis / Q000254:growth & development / Q000378:metabolism*; D014828:Vocalization, Animal
chemical_list: D004343:Drug Implants; D017273:Goserelin; D007987:Gonadotropin-Releasing Hormone
keywords: Cognitive function; GnRH; Gonadotropin releasing hormone; Gonadotropin releasing hormone agonist; Puberty; Sex differences; Sheep; Spatial orientation