ORIGINAL PAPER Rosa Maria Vigueras Æ Gabriela Reyes Norma Moreno-Mendoza Æ Horacio Merchant-Larios Gubernacular fibroblasts express the androgen receptor during testis descent in cryptorchid rats treated with human chorionic gonadotrophin Received: 10 December 2003 / Accepted: 11 February 2004 / Published online: 16 October 2004 Ó Springer-Verlag 2004 Abstract Cryptorchidism was provoked in 3 day old rats treated with 17-b-estradiol over 30 days to identify the cells that express the androgen receptor (AR) during experimental testis descent in the gubernaculum. In one group of animals, testis descent was induced with human chorionic gonadotrophin (hCG) applied daily for 5 or 10 days. A correlative study using a testosterone radio- immunoassay with electron microscopy and immunocy- tochemical detection of AR was performed in gubernacula of hCG treated and untreated control ani- mals. The gubernaculum of rats undergoing testes descent showed a dramatic increase in the number of AR-positive cells. These were located in the connective tissue among smooth muscle cells in the gubernacular cord and between striated muscle fibers in the bulb. In both regions, the AR- positive cells were identified as fibroblasts. Several clusters of amorphous material appeared in the extracellular ma- trix of the connective tissue in hCG treated rats. Our re- sults suggest that testosterone induces the expression of AR in gubernacular fibroblasts which seem to degrade the extracellular matrix during gubernacular involution. Keywords Cryptorchid Æ Gubernaculum Æ Androgen receptor Æ Testis descent Æ Fibroblasts Æ Human chorionic gonadotrophin Introduction The failure of testes to descend into the scrotum, known as cryptorchidism, affects approximately 3% of male children [1]. During development, testicular descent oc- curs in two phases: transabdominal and inguinoscrotal [2]. In the rat, the transabdominal phase occurs during days 16–19 of gestation and the inguinoscrotal phase starts at day 19 of gestation; complete descent is accomplished around day 21 after birth [3, 4]. The gubernaculum, first described by John Hunter [5] as a fibrous structure that anchors the testicle and the epididymis to the floor of the scrotum, is required for testis descent. In the rat, the gubernaculum forms be- tween days 14 and 15 of gestation [3]. In this species, the gubernaculum has two regions: the cranial gubernacular cord connecting the testicle and the epididymis and the caudal gubernacular bulb expanding to the retro- abdominal wall. Histologically, the gubernaculum is composed of mesenchymal cells and abundant extra- cellular matrix, rich in glycosaminoglycans and collagen [4, 5, 6] as well as striated muscle fibers [3, 4, 7]. The cellular mechanisms underlying inguinoscrotal testis descent remain unclear. Active cell processes occurring in the gubernaculum during its size reduction may be involved: cell proliferation, differentiation and migration [8, 9, 10]. Furthermore, since the gubernacu- lum pulls down the testis by reducing its size, some au- thors have suggested gubernacular muscle contraction as the main process for testis descent [7, 11]. However, others consider that active regulation of the gubernac- ular involution underlies inguinoscrotal testis descent [3, 4, 12]. Whatever the reason, it is widely accepted that the inguinoscrotal phase of testis descent depends substan- tially on androgens [1, 2, 13, 14]. In the rat, androgen receptors (AR) are present in gubernacular cells between days 15 and 18 of gestation with a fall just before the final migration of the testicle [15, 16, 17]. Inguinoscrotal testis descent can be inhibited in animals with the postnatal administration of estradiol [18]. Although in humans with cryptorchidism, the stan- dard form of therapy is surgical orchiopexy, hormone therapy has also been advocated. The most commonly used hormone is human chorionic gonadotrophin (hCG). The latter therapy, however, remains contro- R. M. Vigueras Æ G. Reyes Instituto Nacional de Pediatrı´a, SS. Mexico City, 04530, Mexico N. Moreno-Mendoza Æ H. Merchant-Larios (&) Instituto de Investigaciones Biome´dicas, UNAM, Apartado Postal 70228, Ciudad Universitaria Mexico City 04510 Mexico E-mail: merchant@servidor.unam.mx Urol Res (2004) 32: 386–390 DOI 10.1007/s00240-004-0408-8