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.
Psychoneuroendocrinology. 2013 Sep;38(9):1709-16. doi: 10.1016/j.psyneuen.2013.02.005. Epub 2013 Mar 9.
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.
产前雄激素暴露已被证明可调节大脑发育，导致行为态度、性取向和认知功能发生变化，包括空间信息处理。青春期时促性腺激素的变化是否会导致大脑进一步的组织效应，目前仍知之甚少。本研究旨在评估正常青春期发育前后绵羊模型中空间定向的发育情况，该模型中一半动物由于促性腺激素释放激素受体（GnRHR）信号的药理学阻断而未经历典型的生殖成熟。该研究是一项更大规模试验的一部分，使用了 46 对同性苏格兰穆勒-泰塞尔十字羊双胞胎（22 只雌性和 24 只雄性）。一只双胞胎始终未接受治疗（对照组），而另一只则每四周接受一次皮下 GnRH 激动剂（GnRHa：醋酸戈舍瑞林）植入物。GnRHa 治疗分别于雄性 8 周和 28 周、雌性 28 周开始，因为绵羊的青春期过渡时间与人类一样存在性别差异。空间定向在三个不同时间点进行评估：8 周龄，青春期前和两性治疗前；28 周龄，雄性 20 周 GnRHa 治疗后和雌性青春期前及 GnRHa 治疗前；48 周龄，两性正常青春期过渡后。空间定向在空间迷宫中进行测试，以穿越时间作为主要测量指标。GnRHa 治疗并未影响空间迷宫表现，因为在任何时间点，治疗组和未治疗组动物的穿越时间均无显著差异。青春期雌性（48 周龄）穿越迷宫的速度明显快于青春期雄性，而在早期发育阶段（8 周和 28 周）则没有性别差异。空间定向的性别差异发展与青春期激素暴露无关，因为青春期阻断和对照组动物的空间迷宫表现模式相同。这一结果表明空间定向发展具有产前性质。此外，令人意外的是，雌性动物在空间定向任务中的表现优于雄性，这突出了测试环境在空间定向实验中的重要性。
