Fig. 3.

Sustained COUP-TFII to epididymal agenesis and altered sperm maturation (AOP3). Leydig cells are the cellular target for KE1, the epididymis is the target organ leading to altered sperm maturation as the AOs. KEs outlined in blue are proposed to occur during the MPW. KEs are aligned to the developmental timeline such that events sharing the same vertical plane occur in the same developmental window. The horizontal planes depict: 1) biological process occurring, 2) embryonic day (E), 3) AOP, and 4) subset of data that supports the pathway being specific to the indicated developmental window. These data demonstrate a single dose of the AR antagonist flutamide causes different effects on the epididymis (when measured at PND95-105) depending on when in gestation the exposure occurs (red circles indicates timing of single exposure) (Foster and Harris, 2005); extending the duration of flutamide exposure to include the late gestational window (red filled bars) leads to an earlier onset of observable epididymal lesions (E21.5) and higher incidence later in life (PND17, PND42 & PND70) than flutamide exposure during the MPW only; and treatment during the late gestational window (open bar) has no effects on the epididymis (E21.5, PND17, PND42, & PND70). Note: KEs are numbered according to the network (Fig. 4). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)