The Sertoli cells in the testes of Rattus fuscipes have been studied during the seasonal reproductive cycle of this Australian rodent using light and electron microscopy combined with the measurement of androgen binding protein (ABP) in cytosols from testis and caput epididymis. During the winter months when spermatogenesis was arrested and the testes were regressed, serum FSH, LH and testosterone levels were significantly lower than in the summer period, when the animals were sexually active. In the period of sexual quiescence, the seminiferous tubule diameter was decreased and the epithelium consisted of Sertoli cells and spermatogonia. The height of the Sertoli cells was reduced and the nucleus was displaced toward the lumen. The nucleus was ovoid and decreased in size compared with the active state. Chromatin clumps were found adjacent to the nuclear membrane in contrast to the homogeneous nucleoplasm found in the Sertoli cell of the active testis. Diminished quantities of smooth endoplasmic reticulum and an accumulation of lipid droplets in the Sertoli cell cytoplasm also characterized the regressed state. Levels of ABP in cytosols prepared from testes and caput epididymides were significantly lower in the nonbreeding season, indicating reduced secretory function of the Sertoli cell.

One month after the induction of cryptorchidism in adult rats, serum levels of LH and FSH were significantly elevated in comparison with sham-operated controls, whereas serum levels of testosterone remained low to normal. Testis weight in cryptorchid rats was reduced by over 66%, and once the extratubular fluid was removed by decapsulation, the reduction in weight was 78%. The basal production of testosterone, pregnenolone, and estradiol in vitro by testes from cryptorchid rats was similar to controls, whereas significantly less androstenedione was produced. Testicular stimulation in vitro with a high dose of hCG (360 pM) resulted in significantly greater production of testosterone, pregnenolone, and estradiol by cryptorchid than by control rat tissue. The in vitro binding of [125I]hCG per testis was decreased in the cryptorchid state to 40% of control values, probably as a result of down-regulation of LH receptors due to the 4-fold elevation of serum LH levels in the cryptorchid rats.

The cytology and bacteriology of urethral urine specimens and expressed prostatic secretions were examined in 24 infertile men suspected of having chronic prostatitis. Lencocytes were found and commensal bacteria cultured from most subjects but these were unrelated to clinical features, seminal characteristics or the outcome of treatment. Infection with pathogenic bacteria was not found in any subject. Despite this, there was a significant increase in sperm motility after antibacterial treatment, principally with erythromycin or cotrimoxazole, and three pregnancies coincided with the improvement. It is concluded that antibacterial therapy may improve fertility in patients with low sperm motility, but more investigation is necessary before the role of genital tract infection in male infertility can be placed in its proper perspective.

The amount of [125I]human chorionic gonadotrophin bound by testicular membrane preparations from adult male rats with germinal cell aplasia induced by x‐irradiation in utero was significantly reduced in comparison to that of normal males. The in vivo serum testosterone response to an injection of human chorionic gonadotrophin was significantly decreased in the x‐irradiated rats. Paradoxically, the in vitro maximal secretory response to gonadotrophin stimulation was markedly increased. It is concluded that a decrease in the number of receptors on Leydig cells subjected to chronically elevated serum levels of LH does not limit the capacity of the testis for steroid biosynthesis.

It is not possible to undertake a discussion of the regulation of spermatogenesis without properly understanding the key steps in sperm production, and details of this process have been extensively reviewed (de Kretser & kerr, 1994: Sharpe, 1994). In the adult mammal, spermatogenesis, when fully established, can be subdivided into three essential phases: (1) the replication of stem cells, (2) the meiotic process, and (3) spermiogenesis.

Within 7 days of the surgical induction of cryptorchidism, the Sertoli cells demonstrated an accumulation of lipid inclusions and dilatations of smooth endoplasmic reticulum. Aggregations of large vacuoles were observed at the basal aspects of the Sertoli cells and appeared to arise from local dilatations of the intercellular spaces between opposing inter-Sertoli cell junctions. These modifications of the inter-Sertoli cell junctional complexes disappeared as the cryptorchid state persisted, though some observations suggest that the associated membranes form complexly arranged bodies. The function of the Sertoli cells was altered in the cryptorchid testis as demonstrated by severe reduction in androgen binding protein (ABP) production by the 4 week cryptorchid testis and the lack of measureable ABP within the caput epididymidis. Serum FSH and LH levels became significantly elevated within 14 days of establishing cryptorchidism, suggesting diminished feedback from the damaged testis. Continuation of cryptorchidism was associated with progressive widening and folding of the peritubular tissue of the seminiferous tubule leading to bizarre arrangements of the tunica propria. The results are consistent with the proposal that in association with degeneration of the germ cells of the cryptorchid testis, the structure and function of the Sertoli cells are acutely sensitive to the raised intra-abdominal temperature.

International Journal of AndrologyVolume 1, Issue s1 p. 66-75 Free Access Medical Therapy for Infertility D. M. de Kretser, D. M. de Kretser Monash University, Department of Anatomy, Clayton, Victoria, Australia 3168Search for more papers by this author D. M. de Kretser, D. M. de Kretser Monash University, Department of Anatomy, Clayton, Victoria, Australia 3168Search for more papers by this author First published: October 1978 https://doi.org/10.1111/j.1365-2605.1978.tb00490.xCitations: 2AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat References Barwin B. N. Intrauterine insemination of husband's semen. J. Reprod. Fert. 36, 101 (1974). Billings E. L., J. J. Billings, J. E. Brown and H. G. Burger (1972) Symptoms and hormonal changes accompanying ovulation. Lancet 1, 282. Charny C. Y. (1956) Treatment of male infertility with large doses of testosterone, J.A.M.A. 160, 98. de Kretser D. M. (1974) The management of the infertile male. Clinics in Obstet. and Gynaecol. 1, 409. de Kretser D. M., H. G. Burger, B. Hudson and E. J. Keogh (1974) Effects of shortterm administration of clomiphene citrate on serum FSH and LH levels in men with idiopathic disorders of spermatogenesis, Andrologia 6, 25. De Louvois J., M. Polades, R. F. Harrison, R. Hurley and V. C. Stanley (1974) Frequency of mycoplasma in fertile and infertile couples. Lancet 1, 1073. Fairley K. F., J. U. Barrie and W. Johnson (1972) Sterility and testicular atrophy related to cyclophosphamide therapy, Lancet 1, 568. Friberg J. and H. Gnarpe Mycoplasma infections and infertility. In Male Fertility and Sterility, R. E. Mancini and L. Martini (eds.), Academic Press, London , p. 327. Fogh-Andersen P., N. C. Nielsen, H. Rebbe and G. Stakemann (1975) The effect on fertility of ligation of the left spermatic vein in men without clinical signs of varicocele, Acta Obstet. Gynec. Scand. 54: 29. Heller C. G. (1961) Endocrine dysfunction and infertility. In: Report of the 35th Ross Conference on Paediatric Research, S. J. Fomon (ed.), Ross Laboratories, Columbus , Ohio . Heller C. G. and Y. Clermont (1964) Kinetics of the germinal epithelium in man, Recent Prog. Horm. Res. 20, 545. Heller C. G., W. O. Nelson, I. C. Hill, E. Henderson, W. O. Maddock, Jungck, E. C., C. A. Paulsen and G. E. Mortimore (1950) Improvement in spermatogenesis following depression of human testes with testosterone, Fertil. Steril. 1, 415. Heller C. G., M. J. Rowley and G. V. Heller (1969) Clomiphene citrate: A correlation of its effect on sperm concentration and morphology, total gonadotropins, ICSH, tstrogen and testosterone excreted and testicular cytology in normal men, J. Clin. Endocr. Metab. 29, 638. Johnsen, S. G. (1966) A study of human testicular function by the use of human menopausal gonadotrophin and of human chorionic gonadotrophin in males hypogonadotrophic eunuchoidism and infantilism, Acta Endocr. (Kbh.) 53, 315. Kaplan E., H. Shwachman, A. D. Perlmutter, A. Rule, Kon-Taik Khaw and D. S. Holschaw (1969) Reproductive failure in males with cystic fibrosis, New Eng. J. Med. 279, 65. Lunenfeld B., B. Goldman and R. Shalkovsky (1969) Effects of human gonadotropins on spermatogenesis. In Progress in Endocrinology, C. Gual (ed.), Int. Congr. Series 184, Excerpta Medica, Amsterdam , pp. 1044. Macleod J. (1971) Human male infertility, Obstet. Gynec. Survey, 36, 335. Mancini R. E., E. Rosemberg, M. Cullen, J. C. Lavieri, O. Vilar, C. Bergarda and J. A. Andrada (1965) Cryptorchid and scrotal human testes. I. Cytological, cytochemical and quantitative studies, J. Clin, Endocr. Metab. 25, 927. Mancini R. E., O. Vilar, P. Donini and A. Perez Lloret (1971) Effect of human urinary FSH and LH on the recovery of spermatogenesis in hypophysectomized patients. J. Clin, Endocr. Metab. 33, 888. Mellinger R. C. and R. J. Thompson (1966) The effect of clomiphene citrate in male infertility, Fertil. Steril 17, 94. Mor A. and N. Amit (1971) The effect of mesterolone on patients with impaired spermatogenesis and sexual disorders. In Current Problems in Fertility, A. Ingelman-Sundberg and N. O. Lunell (eds.), pp. 231. O'Leary W. M. & J. Frick (1975) The correlation of human male infertility with the presence of mycoplasma T-strains. Andrologia 7, 309. Paulsen C. A. (1965) The effect of human menopausal gonadotrophin on spermatogenesis in hypogonadotrophic hypogonadism. In Proceedings of Pan-American Congress of Endocrinology, Int. Congr. Series 112. Excerpta Medica, Amsterdam , pp. 398. Schellen T. C. M. (1970) Results with mesterolone in the treatment of disturbances in spermatogenesis, Andrologia, 2, 1. Sherins R. J. (1974) Clinical aspects of treatment of male infertility with gonadotrophins: Testicular response of some men given HCG with and without Pergonal, In Male Fertility and Sterility, R. E. Mancini and L. Martini (eds.), Academic Press, London , 545. Stewart-Bentley M., A. Virgi, S. Chang, R. Hiatt and R. Horton (1976) Effect of Dilantin on FSH and spermatogenesis, Clin. Res. 24, 101A. Vilar O. (1974) Effect of cytostatic drugs on human testicular function. In Male Fertility and Sterility, R. E. Mancini and L. Martini (eds.), Academic Press, London , pp. 423. Wang C., H. G. Burger, D. M. de Kretser, A. Dulmanis, B. Hudson, E. J. Keogh and M. B. Suthers (1974) Effect of mesterolone on serum FSH, LH and plasma testosterone in normal men, Andrologia 6, 111. Citing Literature Volume1, Issues1October 1978Pages 66-75 ReferencesRelatedInformation

The effect of differing degrees of destruction of the seminiferous epithelium on serum FSH levels and on Sertoli cell secretory function was studied in adult male rats. Germinal cell aplasia (Sertoli cell-only syndrome, SCO) was induced in male rats by fetal irradiation (250 rads) on day 20 of gestation. Destruction ofthe seminiferous epithelium was induced by treatment with either hydroxyurea (HU) or chronic feeding of a vitamin A-deficient diet (VAD). Serum FSH, LH and testosterone were measured to assess pituitary-testicular interaction, and testicular androgen binding protein (ABP) was measured to evaluate Sertoli cell secretory function in these states. Serum LH was significantly elevated in all three treatment groups, while serum testosterone was significantly lower than normal only in SCO rats. The elevation of LH and the lowered testosterone levels suggest that there is partial Leydig cell failure in rats with germinal cell aplasia induced by fetal irradiation. Significantly elevated levels of serum FSH were seen in all three treatment groups; the degree of elevation was proportional to the severity ofthe induced testicular damage (normal adult males 378 ± 27, HU treated 751 ± 28, VAD 1019 ±49 and SCO rats 1070 ± 54 ng/ml, mean ± SEM). Both the secretion rate of ABP as measured by its accumulation in the testis in the 16 h following efferent duct ligation, and the total amount of ABP both in testis and caput epididymis were markedly decreased in all three treatment groups in proportion to the severity of the induced testicular damage. These findings indicate that Sertoli cell secretory function was impaired as a result of the treatments used to induce testicular damage. The demonstration of impaired Sertoli cell secretory function in association with elevated serum FSH suggests that feedback regulation of FSH may be a function ofthe Sertoli cell.

Constant iv infusions of TRH for 4 h were administered to normal men in dosages of 0.5 (n = 5), 2.0 (n = 10) and 5.0 (n = 4) μg/min and to women in a dosage of 0.5 μg/min (n = 4). Control 4-h saline infusions were performed in 4 men and 4 women. Measurements at regular intervals were made for serum levels of TSH, PRL, T4, T3 and 3,3′,5′-triiodo-L-thyronine (reverse triiodothyronine or rT3). Serum levels of TSH increased in 2 phases. The first phase started within 5 min after the infusions began and reached a plateau at approximately 50 min which lasted until 90 min. After 90 min, a second phase of increase in serum TSH levels occurred which continued until 120 to 150 min. The two phases of increase could reflect the existence of two pools of TSH in the pituitary, one requiring longer stimulation for release than the other, as has been suggested for LH. In contrast, serum levels of PRL during the same infusions reached maximal values by 30 to 45 min and then declined gradually in spite of continued TRH stimulation, with no second phase of increase. Serum levels of T3 were significantly increased by 180 min during the infusion of all TRH dosages used. Levels of T4 were significantly increased by 240 min during the 2.0 and 5.0 μg/min infusions. No significant increases were found in rT3. These results are consistent with the interpretation that the major source of circulating rT3 is not the thyroid, but peripheral deiodination of T4.

Luteinizing hormone releasing hormone (LHRH) was administered to adult rams as constant intravenous infusions lasting 4 to 6 h. Dosages of 0.05, 0.1, 0.5 and 1.0 ug/min were used. All studies were undertaken during the period of decreasing day length (January to June). Plasma luteinizing hormone (LH) values during administration of the two highest dosages revealed a biphasic pattern of increase during the first 2 h of the infusion, as has been found in similar studies in humans. LH values were maximal at approximately 2½ h of the infusions, then decreased in spite of continued LHRH administration, thereby demonstrating the development of pituitary refractoriness during prolonged LHRH administration. A similar refractory period has not been noted during analogous studies in men. Plasma follicle stimulating hormone (FSH) values generally increased gradually during LHRH infusions, with no evidence of a biphasic pattern. No FSH increase was noted in some studies, even at the highest LHRH dosage used.

Most clinical trials in males utilize chemical means to induce temporary infertility. These guidelines are recommended to improve the safety of performing such trials as well as the evaluation of possible drug-related adverse hepatic reactions.