Erratum: Development of the Penile Urethra in the Tammar Wallaby

Hypospadias is increasingly common, and requires surgery to repair, but its aetiology is poorly understood. The marsupial tammar wallaby provides a unique opportunity to study hypospadias because penile differentiation occurs postnatally. Androgens are responsible for penile development in the tammar, but the majority of differentiation, in particular formation and closure of the urethral groove forming the penile urethra in males, occurs when there is no measurable sex difference in the concentrations of testosterone, dihydrotestosterone or androstanediol in either the gonads or the circulation. Phalluses were examined morphologically from the sexually indifferent period (when androgens are high) to well after the time that the phallus becomes sexually dimorphic. We show that penile development and critical changes in the positioning of the urethra occur in the male phallus begin during an early window of time when androgens are high. Remodelling of the urethra in the male occurs between days 20–60. The critical period of time for the establishment urethral closure occurs during the earliest phases of penile development. This study suggests that there is an early window of time before day 60 when androgen imprinting must occur for normal penile development and closure of the urethral groove.

尿道下裂（Hypospadias）的发病率日益升高，临床需通过手术修复，但目前对其病因学（aetiology）的认知仍十分有限。袋类动物塔马尔沙袋鼠（tammar wallaby）为尿道下裂的研究提供了独特契机，因其阴茎分化过程发生于出生后。塔马尔沙袋鼠的阴茎发育依赖雄激素调控，但绝大多数分化环节——尤其是雄性构建阴茎尿道所需的尿道沟形成与闭合过程——发生时，其性腺或血液循环中的睾酮、二氢睾酮及雄烷二醇浓度均无可检测到的性别差异。研究人员对从性未分化期（此时雄激素水平处于高位）至阴茎完全呈现性二态性之后的多个时间点的阴茎组织进行了形态学分析。结果显示，雄性阴茎发育及尿道位置的关键变化，起始于雄激素水平较高的早期窗口期。雄性尿道的重塑过程发生于出生后第20至60天之间。尿道闭合建立的关键时期恰好处于阴茎发育的最早期阶段。本研究表明，在出生后第60天之前存在一个早期窗口期，此时必须完成雄激素印记，才能保障阴茎正常发育及尿道沟的闭合。