ANDROGEN ACTION DURING MALE SEX-DIFFERENTIATION INCLUDES SUPPRESSION OF CRANIAL SUSPENSORY LIGAMENT DEVELOPMENT

The cranial suspensory ligament is located on the border of the crania l (mesonephric) mesentery in adult female mammals, which runs between the cranial pole of the internal genitalia and the dorsal abdominal wa ll. Absence of the cranial suspensory ligament in male mammals depends upon exposure of its primordium to fetal testicular androgens and is a prerequisite for testis descent. Female rats were exposed to 5 alpha -dihydrotestosterone propionate at different stages of genital develop ment, and cranial suspensory ligament development was studied in neona tal and in adult animals, Androgens suppressed cranial suspensory liga ment development when exposure started during the early stages of geni tal development, until day 19 postconception (pc), Androgen receptor e xpression was immunohistochemically detected in the cranial mesentery of both sexes from day 16 pc onwards. A decrease of androgen receptor expression in female fetuses from day 18 pc onwards coincided with the appearance of a differentiated cranial suspensory ligament, as eviden ced by the expression of two cell differentiation markers: a-smooth mu scle (alpha-SM) actin and desmin, alpha-SM actin was located on the ou ter border of the cranial mesentery of both sexes at day 17 pc, and ex pression increased only in female fetuses, On day 19 pc, desmin expres sion was also detectable in the alpha-SM actin-positive cells. Prolife ration and apoptosis indices of cells in the cranial mesentery, as ana lysed by 5'-bromodeoxyuridine incorporation and by detection of DNA st rand breaks (TUNEL method) respectively, did not show any difference b etween the sexes, neither on day 17 nor on day 18 pc. Since primordial cells of the cranial suspensory ligament highly express the androgen receptor during the period of gestation when androgens can suppress cr anial suspensory development, altered morphogenesis of these cells may be a direct consequence of androgen action.