Edinburgh Napier University

  A testicular dysgenesis-like syndrome is induced in rats by fetal exposure todi(n-butyl) phthalate (DBP). A key feature of this is the formation of focal dys-genetic areas comprising malformed seminiferous cords⁄tubules and intratubu-lar Leydig cells (ITLC), but how and why these arise remains unclear. Thepresent study has used combinations of cell-specific markers and immunohisto-chemistry to address this. The results show that focal dysgenetic areas andITLC first appear postnatally at 4–10 days of age, but this only occurs in treat-ment groups in which formation of fetal Leydig cell aggregation is inducedbetween e17.5 and e21.5. Extreme variability in the formation and size of theLeydig cell aggregates probably accounts for the equally extreme variation inoccurrence and size of focal dysgenetic areas postnatally. DBP-induced fetalLeydig cell aggregation traps Sertoli and other cells within the aggregates, but itis unclear why this happens nor why cords fail to form prenatally in these cellmixtures but do elsewhere in the fetal testis. The present studies show that dif-ferentiation of the fetal Leydig cells is drastically delayed at e15.5 after DBPexposure, which may be indicative of a wider delay in testis cell developmentand organisation, and this might account for some of the unexplained findings.