Normal regression (involution) of the X-zone in females of many mouse strains, including the B6C3F1 strain, progresses in morphologically distinct stages. The onset of regression begins with vacuolization of scattered constituent cells (Figure 1 and Figure 2). As regression continues, the number of vacuolated cells progressively increases until virtually all X-zone cells are affected. In later stages, the vacuolated X-zone cells undergo degeneration and necrosis, with subsequent overall X-zone architectural collapse, condensation, and eventual disappearance. A common end-stage sequela is the residual accumulation of pigment-laden cells in the perimedullary area formerly occupied by the X-zone. In males, X-zone regression is similar except that it usually occurs without vacuolization.
The function of the X-zone is unknown. Its normal development and regression are mediated by gonadal and thyroid hormones, so factors that alter levels of these hormones can affect the X-zone. For example, gonadectomy prolongs the persistence of the X-zone in female mice and prepubertal male mice and can cause the reappearance of the X-zone in postpubertal males. Administration of androgens like testosterone is followed by rapid disappearance of the X-zone in female mice. Administration of certain other chemicals can also affect the X-zone, resulting in asynchronous deviations, such as accelerated regression (Figure 3 and Figure 4) in treated groups compared with age-matched concurrent controls (Figure 1 and Figure 2).
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