The cranial suspensory ligament (CSL) is a fibromuscular structure anchoring the embryonic gonad to the posterior abdominal wall in male and female mammals. Its persistence in females is believed to be responsible for retaining the ovaries within the abdomen, while its regression in males permits testis descent. Embryonic loss of the CSL in males is believed to be an androgen-dependent event, and failure of this process has been proposed as a cause of cryptorchidism. The present study demonstrates that the nuclei of mesenchymal cells in the caudal part of the CSL are immunoreactively positive for androgen receptor. We examined the effects of exposure of the non-steroidal antiandrogen flutamide during the period from gestational day 10 to birth on the development of the CSL and on testis descent. Exposure of male Albino Swiss rats to the antiandrogen flutamide during this period resulted in feminization of the external genitalia and the suppression of growth of the testes and male reproductive tracts. In adulthood, testes were found to be located in diverse positions including normal scrotal (50%), intra-abdominal (10%) and ectopic suprainguinal (40%). The CSL of the testis persisted into adulthood in all flutamide-treated males, regardless of testis location. In all cases, the ligament consisted of bundles of smooth muscle fibres in the retroperitoneal fat of the posterior abdominal wall. These findings suggest that androgen blockade during embryonic development interferes with testicular descent, but that maldescent cannot be correlated with either the persistence of the CSL of the testis or its structure.

Backhouse, K.M. (1982) Embryology of testicular descent and mal-descent. Urol Clin North Am 9: 315–325.
Bartlett, J.E., S.M.Y. Lee, Y. Mishina, R.R. Behringer, N. Yang, J. Wolf, C. Temelcos, J.M. Hutson (2002) Gubernacular development in Mullerian inhibiting substance receptor-deficient mice. BJU Int 89: 113–118.
Barthold, J.S., H.R. Mahler, B.W. Newton (1994) Lack of feminisation of the cremaster nucleus in cryptorchid androgen insensitive rats. J Urol 152: 2280–2286.
Baumans, V., G. Dijkstra, C.J.G. Wensing (1983) The role of a non-androgenic testicular factor in the process of testicular descent in the dog. Int J Androl 6: 541–552.
Benten, W.P.M., M. Lieberherr, O. Stamm, C. Wrehlke, Z. Guo, F. Wunderlich (1999) Testosterone signalling through internalizable surface receptors in androgen receptor-free macrophages. Mol Biol Cell 10: 3113–3123.
Denmeade, S.R., J.T. Isaacs (1996) Activation of programmed (apoptotic) cell death for the treatment of prostatic cancer. Adv Pharmacol 35: 281–306.
Elder, J.S. (1987) Cryptorchidism: isolated and associated with other genitourinary defects. Pediatr Clin North Am 34: 1033–1053.
Engle, E.T. (1932) Experimentally-induced descent of the testes in the Macacus monkey by hormones from the anterior pituitary and pregnancy urine. The role of the gonadokinetic hormones in pregnancy blood in the normal descent of the testes in man. Endocrinology 16: 513–520.
Evans, R.M. (1988) The steroid and thyroid hormone receptor superfamily. Science 240: 889–895.
Fentener van Vlissingen, J.M., E.J.J. van Zoelen, P.J.F. Ursem, C.J.G. Wensing (1988) In vitro model of the first phase of testicular descent: Identification of a low molecular weight factor from fetal testis involved in proliferation of gubernaculums testis cells and distinct from specified polypeptide growth factors and fetal gonadal hormones. Endocrinology 123: 2868–2877.
Frey, H.L., J. Rajfer (1982) Incidence of cryptorchidism. Urol Clin North Am 9: 327–329.
Freeman, S. (1990) The evolution of the scrotum: a new hypothesis. J Theor Biol 145: 429–445.
Gabella, G. (1976) The force generated by a visceral smooth muscle. J Physiol 263: 199–213.
George, F.W. (1989) Developmental pattern of 5α-reductase activity in the rat gubernaculum. Endocrinology 124: 727–732.
George, F.W., K.G. Peterson (1988) Partial characterization of the androgen receptor of the newborn rat gubernaculum. Biol Reprod 39: 536–539.
Heinlein, C.A., C. Chang (2002) The roles of androgen receptors and androgen-binding proteins in nonandrogenic actions. Mol Endocr 16: 2181–2187.
Heyns, C.F., V.C. Pape (1991) Presense of a low capacity androgen receptor in the gubernaculum of the pig fetus. J Urol 145: 161–167.
Husmann, D.A., T.B. Boone, M.J. McPhaul (1994) Flutamide-induced testicular undescent in the rat is associated with alterations in genitofemoral nerve morphology. J Urol 151: 509–513.
Husmann, D.A., M.J. McPhaul (1991a) Localization of the androgen receptor in the developing rat gubernaculum. Endocrinology 128: 383–387.
Husmann, D.A., M.J. McPhaul (1991b) Time-specific androgen blockade with flutamide inhibits testicular descent in the rat. Endocrinology 129: 1409–1416.
Hutson, J.M., P.K. Donahoe (1986) The hormonal control of testicular descent. Endocr Rev 7: 270–283.
Hutson, J.M., S. Hasthorpe (2005) Abnormalities of testicular descent. Cell Tissue Res 322: 155–158.
Hutson, J.M., M. Terada, B. Zhou, M.P.L. Williams (1996) Normal testicular descent and the aetiology of cryptorchidism. Adv Anat Embryol Cell Biol 132: 1–56.
Hutson, J.M., M.P.L. Williams, M.E. Fallat, A. Attah (1990) Testicular descent: new insights into its hormonal control. Oxf Rev Reprod Biol 12: 1–56.
Jensen, E.V. (1996) Steroid hormones, receptors, and antagonists. Ann NY Acad Sci 748: 1–17.
Kassim, N.M., S.W. MCDonald, O. Reid, N.K. Bennett, D.P. Gilmore, A.P. Payne (1997) The effects of pre- and postnatal exposure to the non-steroidal anti-androgen flutamide on testis descent and morphology in the Albino Swiss rat. J Anat 190: 577–588.
Kersten, W., G.J. Molenaar, J.M.A. Emmen, P. van der Schoot (1996) Bilateral cryptorchidism in a dog with persistent cranial testis suspensory ligaments and inverted gubernacula; report of a case with implications for understanding normal and aberrant testis descent. J Anat 189: 171–176.
Lawrence, I.E. Jr., H.W. Burden (1980) The origin of the extrinsic adrenergic innervation to the rat ovary. Anat Rec 196: 51–59.
Lee, H.-J., C. Chang (2003) Recent advances in androgen receptor action. Cell Mol Life Sci 60: 1613–1622.
Lee, S.M.Y., J.M. Hutson (1999) Effects of androgens on cranial suspensory ligament and ovarian position. Anat Rec 255: 306–315.
Melton, C.E., J.T. Saldivar Jr. (1970) Activity of the rat’s uterine ligament. Am J Physiol 219: 122–125.
Nef, S., L. Parada (1999) Cryptorchidism in mice mutant from INSL3. Nat Genet 22: 295–299.
Peng, Y., F. Chen, J. Melamed, L. Chiriboga, J. Wei, X. Kong, M. McLeod, Y. Li, C.X. Li, A. Feng, M.J. Garabedian, Z. Wang, R.G. Roeder, P. Lee (2008) Distinct nuclear and cytoplasmic functions of androgen receptor cofactor p44 and association with androgen-independent prostate cancer. Proc Natl Acad Sci USA 105: 5236–5241.
Reynolds, E.S. (1963) The use of lead citrate at high pH as an electron-opaque stain in electron microscopy. J Cell Biol 17: 208–212.
Spencer, J.R., E. Darracott Vaughan Jr., J. Imperato-McGinley (1993) Studies of hormonal control of postnatal testicular descent in the rat. J Urol 149: 618–623.
Spencer, J.R., T. Torrado, R.S. Sanchez, E. Darracott Vaughan Jr., J. Imperato-McGinley (1991) Effects of flutamide and finasteride on rat testicular descent. Endocrinology 129: 741–748.
Tomiyama, H., J.M. Hutson, A. Truong, A.I. Agoulnik (2003) Transabdominal testicular descent is disrupted in mice with deletion of insulin-like factor 3 receptor. J Paediatr Surg 38: 1793–1798.
Tsai, M.J., B.W. O’Malley (1994) Molecular mechanisms of action of steroid/thyroid receptor superfamily members. Annu Rev Biochem 63: 451–486.
Van der Schoot, P. (1992a) Androgen in relation to prenatal development and postnatal inversion of the gubernaculum in rats. J Reprod Fertil 95: 145–158.
Van der Schoot, P. (1992b) Disturbed testicular descent in the rat after prenatal exposure to the anti-androgen flutamide. J Reprod Fertil 96: 483–496.
Van der Schoot, P., W. Elger (1992) Androgen-induced prevention of the outgrowth of cranial gonadal suspensory ligaments in fetal rats. J Androl 13: 534–542.
Van der Schoot, P., J.M. Emmen (1996) Development, structure and function of the cranial suspensory ligaments of the mammalian gonads in a cross species perspective; their possible role in effecting disturbed testicular descent. Hum Reprod Update 2: 399–418.
Wensing, C.J.G. (1986) Testicular descent in the rat and a comparison of this process in the rat with that in the pig. Anat Rec 214: 154–160.
Wensing, C.J.G., B. Colenbrander (1986) Normal and abnormal testicular descent. Oxf Rev Reprod Biol 8: 130–164.
Whitacre, D.C., S. Chauhan, T. Davis, D. Gordon, A.E. Cress, R.L. Miesfeld (2002) Androgen induction of in vitro prostate cell differentiation. Cell Growth Differ 13: 1–11.
Yuan, F.P., D.X. Lin, C.V. Rao, Z.M. Lei (2006) Cryptorchidism in LhrKO animals and the effect of testosterone replacement therapy. Hum Reprod 21: 936–942.
Yuan, S., J. Trachtenberg, G.B. Mills, T.J. Brown, F. Xu, A. Keating (1993) Androgen-induced inhibition of cell proliferation in an androgen-insensitive prostate cancer cell line (PC-3) transfected with a human androgen receptor complementary DNA. Cancer Res 53: 1304–1311.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.