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Biomedical subjects

B P Setchell

Publications and source records attributed to B P Setchell.

At least 19 recordsLinked to original sources

Failure of thyroid allografts to function in the testes of cynomolgous monkeys.

Allografts of thyroid were placed into one testis of 8 cynomolgous monkeys. None of these had accumulated significant amounts of radioactive iodide 28 days later, whereas autografts of thyroid placed in the other testis of 6 of these monkeys did so in 5 cases out of the 6. Autografts of thyroid placed subcutaneously in these 6 monkeys also accumulated iodide in the same 5 animals, but subcutaneous allografts failed in all 6 monkeys in which these were done. These results suggest that there is no immune privilege for grafts in the primate testis, which in this regard resembles more the testis of the ram, rather than that of rodents.

Animals

Effect of testicular temperature on vasomotion and blood flow.

Vasomotion (spontaneous rhythmic variations in blood flow) has been demonstrated in the parenchyma of the testes of anaesthetized rats, using a laser-Doppler flow probe. As the temperature of the testis was increased, mean blood flow showed no change, but the frequency of vasomotion increased and its amplitude decreased, until vasomotion disappeared between 36 degrees C and 42 degrees C. As the testis was then cooled, vasomotion reappeared, and increased in amplitude and decreased in frequency as the temperature fell. In control rats, in which the temperature of the testes was maintained at normal scrotal temperature of about 33 degrees C, there no changes in vasomotion over an equivalent period. In both groups of rats, when the temperature of the testes was then allowed to fall below normal scrotal temperature, the amplitude of vasomotion increased and its frequency decreased even further, without any change in mean blood flow. Capillary blood flow was also measured with microspheres at the end of the experiment, when testicular temperature was between 19 degrees C and 27 degrees C, and there was no difference between the cooled and control testes or epididymides.

Animals

Effect of active immunization against oestradiol in developing ram lambs on plasma gonadotrophin and testosterone concentrations, time of onset of puberty and testicular blood flow.

Merino ram lambs were actively immunized against oestradiol-6 (o-carboxy methyl) oxime-BSA conjugate at 14 weeks of age and received a booster injection 4 weeks later. This treatment led to an increase in plasma concentrations of gonadotrophin and tended to enhance the increase in testicular volume until 26 weeks of age; however, testis size and mass at time of castration (30 weeks of age) were similar to values in BSA-immunized lambs. Detrimental effects were observed in some oestradiol-immunized ram lambs, for example a steep decline in testicular volume towards the end of the experiment, the presence of large vacuoles within the seminiferous epithelium and, in one lamb, few germ cell at 30 weeks of age. Testicular blood plasma flow was significantly reduced in oestradiol-immunized lambs (P < 0.01). The steroidogenic function of the testis was markedly enhanced in oestradiol-immunized lambs as reflected by high plasma concentrations of testosterone measured at 22, 26 and 30 weeks of age and by high testosterone production calculated from blood flow and venous-arterial differences at 30 weeks of age. Nevertheless, total live mass gain over the 16 week study was not increased in oestradiol-immunized lambs. Testicular biopsies were taken at 22 and 26 weeks of age in half of the lambs in each treatment group. Testicular volume measured at castration was decreased in control lambs in which biopsies were taken (P < 0.05), and plasma concentrations of testosterone measured at 30 weeks of age were significantly lower in oestradiol-immunized lambs in which biopsies were taken (P < 0.02) compared with lambs in which no biopsy had been taken. It is concluded that active immunization against oestradiol in ram lambs does not advance the time of onset of puberty and does not confer any reproductive or maturational advantages.

Animals

Effect of active immunization against testosterone on plasma gonadotrophin concentrations, spermatogenic function, testicular blood flow, epididymis mass and mating behaviour in adult rams.

The long-term effects of active immunization against testosterone were studied in rams, with particular reference to blood concentrations of gonadotrophin and testosterone, spermatogenesis, testis blood flow and mating behaviour. Ten 18-month-old Merino rams, kept on pasture, were studied for 1 year. Every 2 months, five rams received injections of BSA in Freund's adjuvant and five other rams were treated with testosterone-3(o-carboxymethyl)oxime-BSA as immunogen. Anti-testosterone antibodies (mean titre: 1:4484 +/- 582, after boosters) were maintained in the circulation, with the help of regular booster injections. In time, immunization reduced live mass in testosterone-immunized rams; however, there was no effect on testicular volume throughout the whole study. In testosterone-immunized rams, significantly higher concentrations of gonadotrophins were found in jugular venous plasma, as well as increased concentrations of total plasma testosterone. LH pulse frequency, amplitude and nadir were increased significantly in testosterone-immunized rams. After 12 months of immunization, no differences were found in the number of spermatozoa per ejaculate, in daily sperm production or in testis mass between the two groups of rams; however, testicular blood flow (per testis) and epididymis mass were significantly reduced in testosterone-immunized rams. Testosterone immuno-neutralization also resulted in a significant reduction in the number of mounts culminating in ejaculation performed during a 10 min trial carried out on a number of occasions during the experiment. Additional information on these rams was collected 3 months after castration. However, there were no significant differences in mean plasma LH and FSH concentrations, either before, or after, a single GnRH injection between the two groups of rams at this time.

Animals

Investigating local regulation of the testes of ruminants.

In addition to endocrine regulation by the gonadotrophic hormones, the functions of the testes are regulated locally by paracrine and autocrine factors. Some attempts have been made to isolate cells from the testes of immature bulls and rams for investigation of cell function in vitro. However, most studies have used in vitro cultures of cells isolated from the testes of rats and a large variety of factors have been identified as potential local regulators. This review examines the importance of Sertoli cell-germ cell interactions, Leydig cells and steroidogenesis, blood flow and vascular permeability, and cytokines and immune cells as local regulators of the testes. The small amount of work undertaken on the testes of ruminants is reviewed together with approaches such as the transilluminated dissection of staged seminiferous tubules and in vivo cell depletion models used with rats. The suitability and limitation of these approaches for ruminants are considered, and immunological and molecular probes are raised as options for future investigations of the local regulation of the testes of ruminants.

Androgens

Possible physiological bases for contraceptive techniques in the male.

Aspects of the physiology of the testis and epididymis are discussed which might be relevant to future methods of contraception in the male. These include the blood-testis barriers, both at the tubular and vascular level, testicular and scrotal thermoregulation and maturation of spermatozoa in the epididymis. Possible adverse consequences of interfering with spermatogenesis are also considered, such as reduced endocrine responsiveness of the testis, increased incidence of genetic abnormalities and abnormal development of embryos produced by sub-fertile males.

Blood-Testis Barrier

Effects of a single brief period of moderate heating of the testes on seminiferous tubules in hypophysectomized rams treated with pituitary extract.

An experiment was conducted to examine the appearance of the seminiferous tubule 20 days after a single exposure of the testes of rams to a scrotal temperature of about 42 degrees C for 45 min. Ten of the animals were surgically hypophysectomized and five were simultaneously heated; these rams were treated twice a day with ovine pituitary extract to avoid modifications in the negative feedback from the testes to the pituitary and consequent changes in gonadotrophin secretion. Six intact rams (three heated and three unheated) were also studied. The pituitary extract significantly increased the testis weight and spermatogonial multiplications from A1 spermatogonia onwards. Twenty days after the heat treatment, testis weight was significantly reduced by heating; both tubular and intertubular tissues were affected. The total length of seminiferous tubules per testis was not modified, whereas the mean seminiferous tubule diameter was significantly reduced after heating. The total number of Sertoli cells per testis was not significantly modified, while their mean cross-sectional nuclear area was significantly reduced by heat treatment. A decrease in the number of all germ cells except A0 spermatogonia, from A1 spermatogonia onwards, was observed. The number of round spermatids decreased by 95 and 90%, slightly more than the diplotene primary spermatocytes (76 and 77%) and elongated spermatids (79 and 85%) in hypophysectomized pituitary extract-treated and intact rams, respectively. Round and elongated spermatids would be derived from germ cells that were respectively leptotene and young pachytene primary spermatocytes at the time of heating, whereas diplotene primary spermatocytes would have been type B spermatogonia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effects of heating the testes and epididymides of rams by scrotal insulation on fertility and embryonic mortality in ewes inseminated with frozen semen.

Fertilization rate and embryonic mortality were assessed in 636 ewes inseminated in each uterine horn with 50 x 10(6) frozen spermatozoa from four control rams and from four rams submitted to a moderate (1.4-2.2 degrees C), but repeated, intermittent (16 h/day for 21 consecutive days) increase in their subcutaneous scrotal temperature by means of scrotal insulation. Pregnancy was assessed twice in each ewe from concentration of progesterone in blood plasma at 17 days and by ultrasound at 65 days after insemination. No differences were observed in the pregnancy rate at 17 days between ewes inseminated with semen collected from control rams (56.0, 65.2, 66.7 and 60.3%) and from heated rams (60.6, 71.8, 63.6 and 48.2%) before or after 4, 15 and 21 days of heating, respectively. In contrast, the rate of embryonic mortality between 17 and 65 days after insemination was significantly higher at days 4, 15 and 21 in the heated rams (78.7, 78.6 and 93%) than in the control rams (55, 59 and 65.7%). These results indicate that an intermittent slight, but repeated, increase in the subcutaneous scrotal temperature could induce a significant increase in the embryonic mortality rate. As these changes were apparent on day 4 of heating, an effect must have occurred on sperm stored in the epididymis.

Animals

Increased flow of testicular blood plasma during local heating of the testes of rams.

After removal of the scrotal skin, one testis of each of 12 adult anaesthetized rams was kept at 33 degrees C for 60 min, then heated either to 36 degrees C for 60 min and then to 39 degrees C for 60 min, or to 36 degrees C for 120 min and then returned to 33 degrees C for 100 min, while the other testis was maintained at 33 degrees C. Flow of testicular blood plasma was measured every 10 min using the technique of dilution of sodium p-aminohippurate. When the temperature of the testis was raised to 36 degrees C, flow of blood plasma gradually increased and reached a higher than normal rate at the end of the first hour, without any further increase during the second hour. The increase in mean flow rate was 25.8 +/- 3.4% (mean +/- SEM) during the second hour at 36 degrees C, and 77.1 +/- 12.8% during the hour at 39 degrees C, compared with the respective values at 33 degrees C. No significant changes were seen in testicular lymph flow determined by collection for 10 min in four rams at 36 degrees C (60 min) and then at 39 degrees C (60 min). These results are different from those from earlier studies in which total blood flow was unchanged when the scrotum and testes were heated. The difference could be related either to lack of heating of the scrotum or to the lower temperatures used in the present study.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Testicular immunosuppressive activity in experimental hypogonadism and cryptorchidism.

The levels of protectin activity were studied in scrotal and abdominal testes and in testes of hypophysectomized and hormone-treated rats to determine whether the prolonged survival of transplants in the abdominal testis was associated with higher protectin activity and whether the protectin activity was dependent on testosterone production. The levels of the testicular high-molecular weight immunosuppressive activity per gram of tissue or per protein concentration rose progressively in the abdominal testis until 7 days after the rats had been made unilaterally cryptorchid. No such increase was observed in the contralateral scrotal testis. In hypophysectomized rats the levels of the testicular immunosuppressive activity were higher than in normal controls. Increase in the serum testosterone concentrations in the hypophysectomized rats obtained by daily treatment with human chorionic gonadotrophin or pregnant mare serum gonadotrophin was associated with significantly lower levels of the testicular immunosuppressive activity as compared to untreated hypophysectomized animals. In the normal rats estradiol treatment increased the levels of testicular immunosuppressive activity as serum testosterone concentrations decreased. In gel filtration there were clear peaks of immunosuppressive activity eluting at 25, 32 and 44 min, corresponding to Mr of greater than 400,000, 200,000 and 25,000, respectively. These results suggest that the levels of testicular immunosuppressive activity increase when testosterone production decreases and support the earlier suggestion that transplant survival in the rodent testis is not dependent on the maintenance of normal testosterone levels in the recipient testis.

Animals

The form and function of the Leydig cells in hypophysectomized rams treated with pituitary extract when spermatogenesis is disrupted by heating the testes.

The morphology and in-vivo function of the Leydig cells were studied in rams when spermatogenesis had been disrupted by a single exposure of the testes 20 days earlier to a temperature of about 42 degrees C for 45 min. To avoid complications due to changed negative feedback from the testes to the pituitary with consequent changes in the degree of gonadotrophic stimulation, ten of the animals (five heated and five unheated) were surgically hypophysectomized when the testes were heated and then treated twice daily with pituitary extract. Six intact rams (three heated and three unheated) were also studied. The heat-affected testes were about half the size of the unheated testes, and blood plasma flow was closely related to testis weight. There were no differences in the testosterone concentrations in spermatic venous blood, testicular lymph or rete testis fluid, or in oestradiol in spermatic venous plasma from heated or unheated testes. Consequently, testosterone secretion by the heat-affected testes was markedly reduced, and the concentrations in jugular blood were also lower in the heat-affected rams than in controls. The volume of the interstitial tissue was less in absolute terms in the heat-affected rams, but it made up a greater fraction of the testes. The absolute volume of the blood plus lymph vessels, and their fraction of the interstitial tissue were lower in the heat-affected testes, although there was no effect on their volume as a fraction of the whole testis. The heat-affected testes of the hormone-treated rams had fewer Leydig cells, but each cell was larger; no equivalent difference was found in the intact rams. However, the dose of pituitary extract chosen was somewhat excessive, as there were higher than normal concentrations of FSH, LH and testosterone in jugular blood plasma, of testosterone and oestradiol in testicular venous blood plasma and of testosterone in rete testis fluid in the hormone-treated hypophysectomized rams. The testes of the unheated hypophysectomized rams increased in size by about 20% during treatment with pituitary extract, although testicular blood plasma flow was lower per unit weight of testis. The absolute volume of each Leydig cell and the total volume in absolute terms and as a fraction of the interstitial tissue was greater in the hormone-treated than in the untreated rams, but not the volume as a fraction of the whole testis. The total number of Leydig cells was higher in the hormone-treated unheated rams than in all the other rams taken together.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

The testis and tissue transplantation: historical aspects.

Transplantation experiments involving the testis have been performed since the days of John Hunter, who transplanted a testis into the belly of a hen. The first person to use the testis as a site of transplantation appears to have been Sand, who found in 1919 that an ovary transplanted into the substance of the testis developed follicles. By 1970, there was considerable evidence that the testis under some circumstances was a relatively favorable site for graft survival. However, much of the evidence was equivocal, and the immunological privilege was by no means complete.

Animals

Recent evidence for immune privilege in the testis.

In the last 20 years, it has been shown that while first-set intra-testicular grafts rarely induce systemic immunity, second-set intra-testicular grafts are usually rejected, if a pre-existing immunity has been generated by first-set skin grafts. These observations suggest that while the efferent limb of the pre-sensitized immune response is operative in the testis, the immune system can not be activated against antigens present only in this site. Various theories have been advanced to explain this phenomenon. The most likely explanation at present seems to be that the testis contains specific immunosuppressive factors that inhibit lymphocyte activation in this site.

Animals

Testis physiology relevant to immunoregulation.

Intra-testicular transplants are placed in rodents into the large lymphatic sinusoids of the interstitial tissue of the testis. These sinusoids are filled with a protein-rich extracellular fluid that supplies all the requirements of the grafts until vascularization takes place. The testicular microvascular endothelium regulates transport of T lymphocytes and immunoglobulin G to the testis and may thus contribute to regulation of the immune system in this organ. Differences in the organization of the lymphatic drainage exist between species, but in every studied species lymphatic drainage from the testis leads to lymph nodes.

Animals

Feeding lupin grain for six days prior to a cloprostenol-induced luteolysis can increase ovulation rate in sheep irrespective of when in the oestrous cycle supplementation commences.

Three groups of 40 parous Merino ewes were supplemented with 500 g of lupin grain/ewe/day for 7 days starting on either Day 3, 7 or 11 of the oestrous cycle and induced to ovulate by injecting cloprostenol on the sixth day of feeding. Supplementation with lupin grain significantly increased ovulation rate in all groups compared with corresponding controls by increasing the proportion of ewes with twin ovulations. Increases in ovulation rate did not depend on the stage of the cycle at which supplementation began or when during the luteal phase luteolysis was induced. It is concluded that the ovulatory response to lupin grain is initiated near the time of luteolysis.

Animal Feed