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Cell-cycle inhibitors p27Kip1 and p21Cip1 regulate murine Sertoli cell proliferation.

Thyroid hormone inhibits neonatal Sertoli cell proliferation and recent results have shown that thyroid hormone upregulates cyclin-dependent kinase inhibitors (CDKIs) p27Kip1 and p21Cip1 (also known as CDKN1B and CDKN1A, respectively) in neonatal Sertoli cells. This suggests that these CDKIs, which negatively regulate the cell cycle, could be critical in Sertoli cell proliferation. Consistent with this hypothesis, mice lacking p27Kip1 develop testicular organomegaly, but Sertoli cell numbers have not been determined. Likewise, effects of loss of p21Cip1 or both p27 and p21 on Sertoli cell number and testicular development were unknown. To determine if p27 and/or p21 regulate Sertoli cell proliferation, we measured Sertoli cell proliferation at Postnatal Day 16 and testis weight, Sertoli cell number, and daily sperm production (DSP) in 4-mo-old wild-type (WT), p21 knockout (p21KO), p27 knockout (p27KO), and p27/p21 double-knockout (DBKO) mice. Testis weights were increased 27%, 42%, and 86% in adult p21KO, p27KO, and DBKO mice, respectively, compared with WT. Sertoli cell number also was increased 48%, 126%, and 126% in p21KO, p27KO, and DBKO mice, respectively, versus WT. DSP in p21KO, p27KO, and DBKO testes also showed significant increases compared with WT mice. Although DSP was increased, there were increased spermatogenic defects observed in both p27KO and DBKO mice compared with WT. These data indicate that both p27 and p21 play an inhibitory role in regulating adult Sertoli cell number such that loss of either CDKI produces primary increases in Sertoli cell number and secondary increases in DSP and testis weight. Furthermore, loss of both CDKIs causes additive effects on DSP and testis weight, suggesting a central role for these CDKIs in testis development.

Animals↗

Luteinizing hormone receptor-mediated effects on initiation of spermatogenesis in gonadotropin-deficient (hpg) mice are replicated by testosterone.

Testosterone (T) is an absolute requirement for spermatogenesis and is supplied by mature Leydig cells stimulated by LH. We previously showed in gonadotropin-deficient hpg mice that T alone initiates qualitatively complete spermatogenesis bypassing LH-dependent Leydig cell maturation and steroidogenesis. However, because maximal T effects do not restore testis weight or germ cell number to wild-type control levels, additional Leydig cell factors may be involved. We therefore examined 1). whether chronic hCG administration to restore Leydig cell maturation and steroidogenesis can restore quantitatively normal spermatogenesis and testis development and 2). whether nonandrogenic Leydig cell products are required to initiate spermatogenesis. Weanling hpg mice were administered hCG (0.1-100 IU i.p. injection three times weekly) or T (1-cm subdermal Silastic implant) for 6 weeks, after which stereological estimates of germinal cell populations, serum and testicular T content, and testis weight were evaluated. Human CG stimulated Leydig cell maturation and normalized testicular T content compared with T treatment where Leydig cells remained immature and inactive. The maximal hCG-induced increases in testis weight and serum T concentrations were similar to those for T treatment and produced complete spermatogenesis characterized by mature, basally located Sertoli cells (SCs) with tripartite nucleoli, condensed haploid sperm, and lumen development. Compared with T treatment, hCG increased spermatogonial numbers, but both hCG and T had similar effects on numbers of spermatocytes and round and elongated spermatids per testis as well as per SC. Nevertheless, testis weight and germ cell numbers per testis and per SC remained well below phenotypically normal controls, confirming the involvement of non-Leydig cell factors such as FSH for quantitative normalization of spermatogenesis. We conclude that hCG stimulation of Leydig cell maturation and steroidogenesis is not required, and that T alone mostly replicates the effects of hCG, to initiate spermatogenesis. Because T is both necessary and sufficient for initiation of spermatogenesis, it is likely that T is the main Leydig cell secretory product involved and that additional LH-dependent Leydig cell factors are not essential for induction of murine spermatogenesis.

Androgens↗

Body weight, food intake and energy regulation in exercising and melatonin-treated Siberian hamsters.

The coupling among energy intake, storage, and expenditure was examined in male Siberian hamsters (Phodopus sungorus sungorus) given access to running wheels for 14 weeks. Half of the hamsters were injected with melatonin in a schedule that mimics the effects of short photoperiods by decreasing body weight, carcass lipid content, and testis weight. The exercise-induced body weight increases which are seen in Syrian hamsters (Mesocricetus auratus) were not found in Siberian hamsters. Instead, the Siberian hamsters maintained their body weights, compensating for the increased energy demands of exercise by increasing their food intakes. Exercise did not affect carcass composition. Melatonin treatment decreased food intake and carcass lipid stores but did not affect voluntary exercise. The previously reported decrease in testis weight was seen in all melatonin-treated hamsters, but the stimulation of brown adipose tissue growth was not. Thus, exercising Siberian hamsters, unlike exercising Syrian hamsters, appear to exhibit a tight coupling among energy intake, storage, and expenditure.

Adipose Tissue, Brown↗

The influence of vasectomy and vasovasostomy on testicular ATPases, cAMP, ABP and androgen receptor in rabbits.

The present study was performed to further clarify the influences of vasectomy on functions of testis and to disclose the possible mechanisms of infertility after vasovasostomy (VV). Thirty-one rabbits were divided into sham-operated control group (C), vasectomy control group (V), VV fertility group (VaF) and VV infertility group (VaI). Serum testosterone (ST) level, testicular cAMP, androgen binding protein (ABP), nuclear androgen receptor (NAR) concentrations, testis cell membrane Na(+)-, K(+)-ATPase, Mg(2+)-ATPase activities, sperm density and testis weight were measured. Vasectomy resulted in significantly reduced cAMP, Na(+)-, K(+)-ATPase, Mg(2+)-ATPase, testis weight and increased ABP; VV completely restore testis weight in VaF and VaI, Na(+)-, K(+)-ATPase, Mg(2+)-ATPase in VaF, partly cAMP in VaF and VaI, Na(+)-, K(+)-ATPase, Mg(2+)-ATPase in VaI, but did not restore ABP. The NAR content in VaI was significantly lower than those in C, VaF and V. No statistical differences among 4 groups were seen in Kd values for [3H]-T. ST levels in VaF, VaI and V were insignificantly different compared with C, but the value in VaF was higher than that in VaI (p < 0.05). Sperm density after VV reached 122 +/- 62 x 10(6)/ml in VaF and 10 +/- 24 x 10(6)/ml in VaI, both in VaF and VaI were significantly low compared with C (p < 0.001), and the value in VaI was remarkedly lower than that in VaF (p < 0.001). It was shown that sperm density was positively correlated with cAMP content, Na(+)-, K(+)-ATPase, Mg(2+)-ATPase activities, but negatively with ABP. These results suggest that vasectomy gives rise to damage to the testis, and vasovasostomy does not appear completely effective in reversing testicular changes.

Adenosine Triphosphatases↗

Quantitative trait loci analysis of heat stress resistance of spermatocytes in the MRL/MpJ mouse.

The MRL/MpJ mouse has previously been reported to possess an interesting phenotype in which spermatocytes are resistant to the abdominal temperature heat shock. In this study genetic analysis for it was performed. The phenotypes of F2 progenies produced by mating MRL/MpJ and control strain C57BL/6 mice were not segregated into two types as parental phenotypes, suggesting that the phenotype is controlled by multiple genetic loci. Thus, quantitative trait loci (QTL) analysis was performed using 98 microsatellite markers. The weight ratio of the cryptorchid testis to the intact testis (testis weight ratio) and the Sertoli cell index were used for quantitative traits. QTL analysis revealed two significant QTLs located on Chrs 1 and 11 for testis weight ratio and one significant QTL located in the same region of Chr 1 for the Sertoli cell index. A microsatellite marker locus located in the peak of the QTL on Chr 1 did not recombine with the exonuclease 1 (Exo1) gene locus in 140 F2 progenies. Mutation of the Exo1 gene was previously reported to be responsible for metaphase-specific apoptosis (MSA) of spermatocytes in the MRL/MpJ mouse. These results raise the possibility that mutation of the Exo1 gene is responsible for both MSA and heat stress resistance of spermatocytes in the MRL/MpJ mouse.

Animals↗

The effect of sampling time on radiation-induced translocation yield in spermatogonial stem cells of male mice, differing in chromosomal constitution and sexual activity.

We have investigated the frequency of reciprocal translocations in the first differentiating spermatogonia entering the first meiotic division after 2 x 2.5 Gy X-rays, given 24 h apart, as well as the development of this parameter in later stem-cell generations by studying multivalent configurations at the first meiotic division. Diakinesis-metaphase I cells were found for the first time between 30 and 40 days after irradiation. Subsequently, meiotic stages were sampled at 120, 180 and 280 days post irradiation. From day 40 post irradiation on, half of the males were allowed to impregnate females which enabled us to estimate the length of the post-irradiation sterile period, the development of litter size and the possible effect of sexual activity on the development of reciprocal translocation-containing stem cells. Half of the males were karyologically normal, the other half were homozygous for a reciprocal translocation (T/T) that affects testis weight and about halves sperm production. Irrespective of male karyotype, the first meiocytes had an induced translocation frequency of 9.00 +/- 2.56% (n = 8 males), followed by frequencies of 20.70 +/- 4.87% (n = 15) at 180 days and 20.20 +/- 4.30% (n = 20) at 280 days (males with and without mating behavior showing no difference). At 120 days post irradiation, +/+ males had a frequency of 14.59 +/- 2.97% irrespective of sexual activity. T/T males (120 days post irradiation) that had mated showed a frequency of 18.63 +/- 0.85% (n = 4) compared with 13.64 +/- 2.36% (n = 7) for those that had not. The observed rise of multivalent-carrying spermatocytes in time was highly significant. Notwithstanding the differences in testis weight and epididymal sperm count between the karyotypes, fertile matings occurred on average 72 days after irradiation, though with relatively wide margins. For the T/T karyotype, the first litter was statistically smaller than the subsequent litters. At 78 days post irradiation, testis weights were back in the subnormal range for both karyotypes and hardly improved in time. Restoration of fertility thus coincided with the period just prior to the return to subnormal testis weights. The first diakinesis-metaphase I cells precede those that are numerous enough to accomplish 'return to fertility' by about 2 weeks. Thus differentiation of stem-cell spermatogonia already follows a few days after irradiation. A pattern of spermatogonial cell divisions compatible with 'return to fertility' is only established some 2 weeks later.

Animals↗

Pattern of change in melatonin duration determines testicular responses in Siberian hamsters, Phodopus sungorus.

The impact of photoperiodic history was studied in male hamsters kept from birth to 6 wk of age (Week 0) in long-day (LD; 16 h light per day) or short-day (SD; 10 h light per day) photoperiods. At Week 0, hamsters were transferred to constant light and were s.c. infused daily with melatonin (MEL; 4 ng/h) until Week 12. Groups of SD hamsters received 10-h MEL infusions or MEL infusions of durations that decreased linearly by 1-2 min/day from 10 h at Week 0 to 7.5 h at Week 12. LD hamsters were infused for 5 h/day or in patterns that decreased from 10 to 7.5 h or increased from 5 to 7.5 h during Weeks 0-12. MEL signals of decreasing duration produced opposite effects on the gonads of LD and SD hamsters: decreasing MEL durations induced complete gonadal regression in LD hamsters (testis weight = 42 +/- 3 mg) but stimulated testis growth in SD hamsters (testis weight = 276 +/- 57 mg; p < 0.05). MEL infusions that were of shorter but increasing duration induced gonadal regression in LD hamsters. The present experiments indicate that MEL signals of a given sequence and duration can produce either gonadal growth or regression depending on the hamster's photoperiodic history. The pattern of change in MEL secretion, as well as absolute duration of the MEL signal, is important for implementing seasonal cycles of reproduction.

Animals↗

The effects of the age of intracerebroventricular grafts of normal preoptic area tissue upon pituitary and gonadal function in hypogonadal (HPG) mice.

Hypogonadal mice are deficient in the hypothalamic gonadotrophic hormone releasing hormone and as a consequence postnatal testicular development does not occur. Grafting preoptic area tissue from normal mice directly into the hypogonadal third ventricle dramatically reverses the hypogonadism; however, the age of the grafted preoptic area tissue is crucial to the survival and function of the graft. Grafting embryonic tissue (E16-18) resulted in 69% of the hypogonadal mice increasing testis weight some sevenfold within 30 days (5.6 to 35 mg). Postnatal day 1 (P1) tissue grafts elicited a similar rise in testis weight in 77% of recipients, whereas P5 tissue was only successful in 22% of cases. In this experimental group, however, testis weight also increased sevenfold compared with hypogonadal untreated mice. Stimulation of testicular growth in the E16-18 and P1 experimental groups was accompanied by an increase in pituitary gonadotrophic hormone content. P10 tissue did not stimulate testis growth nor was pituitary gonadotrophic hormone control elevated and the majority of grafts failed to survive over the 30 day period of the experiment. The present study has shown that the age of grafted tissue is critical in the restoration of physiological function in hypogonadal mice, and that gonadotrophic hormone releasing hormone neurons from E16-18, P1 and P5 preoptic area grafts that survive the 30 day period of the experiment and whose axons reach the median eminence portal vessels are equipotent in stimulating pituitary gonadotrophin synthesis and secretion.

Age Factors↗

Effects of thio-tepa and hydroxyurea on sperm production in Lakeview hamsters.

The spermatogenic cell sensitivity in the induction of sperm abnormalities by two antineoplastic agents, thio-TEPA and hydroxyurea in inbred Lakeview hamsters was studied and the results were compared with those of similar investigations with mice. Testis weights, epididymal sperm numbers, and body weights were also monitored up to 12 wk after treatment. Thio-TEPA administration increased sperm abnormalities and reduced testis weights as well as sperm numbers in a dose-dependent manner at wk 4 and 12 after treatment. Hydroxyurea administration was ineffective in inducing sperm abnormalities, but testis weights and sperm numbers were adversely affected dose-dependent changes in body weights after treatment with either agent were also recorded. The findings with thio-TEPA on sperm morphology agree with those reported for the mouse. However, unlike the results of the mouse studies, hydroxy-urea effects on sperm shape were not observed in the hamster.

Animals↗

Uterine dysfunction and genetic modifiers in centromere protein B-deficient mice.

Centromere protein B (CENP-B) binds constitutively to mammalian centromere repeat DNA and is highly conserved between humans and mouse. Cenpb null mice appear normal but have lower body and testis weights. We demonstrate here that testis-weight reduction is seen in male null mice generated on three different genetic backgrounds (denoted R1, W9.5, and C57), whereas body-weight reduction is dependent on the genetic background as well as the gender of the animals. In addition, Cenpb null females show 31%, 33%, and 44% reduced uterine weights on the R1, W9.5, and C57 backgrounds, respectively. Production of "revertant" mice lacking the targeted frameshift mutation but not the other components of the targeting construct corrected these differences, indicating that the observed phenotype is attributable to Cenpb gene disruption rather than a neighbouring gene effect induced by the targeting construct. The R1 and W9.5 Cenpb null females are reproductively competent but show age-dependent reproductive deterioration leading to a complete breakdown at or before 9 months of age. Reproductive dysfunction is much more severe in the C57 background as Cenpb null females are totally incompetent or are capable of producing no more than one litter. These results implicate a further genetic modifier effect on female reproductive performance. Histology of the uterus reveals normal myometrium and endometrium but grossly disrupted luminal and glandular epithelium. Tissue in situ hybridization demonstrates high Cenpb expression in the uterine epithelium of wild-type animals. This study details the first significant phenotype of Cenpb gene disruption and suggests an important role of Cenpb in uterine morphogenesis and function that may have direct implications for human reproductive pathology.

Animals↗

Antispermatogenic effects of ethyl methanesulfonate and benzo[a]pyrene in PD4 Lakeview hamsters.

Mammalian sperm seems to provide an excellent cell type for monitoring mutagenic and other toxicological damage to the germinal tissue. Studies with mice indicated that most agents known for their mutagenic activity in vivo produced marked elevations in sperm abnormalities. To determine whether this response is typical of other species, groups of inbred Lakeview hamsters were exposed to ethyl methane-sulfonate (EMS) and benzo[a]pyrene (BP) in five daily subacute ip doses ranging from 5 to 125 mg/kg and 2 to 50 mg/kg, respectively. Percentage of abnormal sperm, testis weight, and body weight were monitored at wk 1, 4, and 10 after treatment. EMS exposures increased the frequency of sperm abnormalities and reduced sperm numbers and testis weights. Body weights were also affected. BP exposures did not induce sperm abnormalities; however, there were marked reductions in sperm number and testis weight. These findings are in agreement with results of EMS studies in the mouse; however, BP exposure did induce sperm abnormalities in the mouse.

Animals↗

Peptide and nonpeptide reactive oxygen scavengers provide partial rescue of the testis after torsion.

Ischemia-reperfusion (IR) of the testis results in germ cell-specific apoptosis, followed by a reduction in testis weight and daily sperm production (DSP). This has been associated with an increase in the adhesion of neutrophils to testicular subtunical venules and an increase in reactive oxygen species (ROS). The present study investigated: 1) the effects of a direct, non-IR-related ROS insult to the testis and 2) the effects of catalase, superoxide dismutase (SOD), and a novel nonpeptide mimic of SOD, M40403, on neutrophil recruitment, ROS production, testis weight, and DSP following IR of the rat testis. Results revealed that the infusion of H2O2 increased testicular lipid peroxidation 1 hour after administration and increased germ cell apoptosis within 24 hours of administration. Four hours after the repair of torsion plus vehicle infusion, there was a significant increase in myeloperoxidase (MPO) activity, an indicator of neutrophil accumulation, and thiobarbituric acid reactive substances (TBARS), a measure of ROS production, compared to equivalent data in sham-treated testes. Animals sacrificed 30 days after the torsion plus vehicle infusion revealed a significant decrease in testis weight and DSP compared to the same parameters in sham-operated animals. The treatment of animals with catalase plus SOD or M40403 showed a significant decrease in MPO activity and TBARS 4 hours after IR of the testis. Animals treated with SOD, SOD plus catalase, and M40403 provided a partial rescue of DSP 30 days after IR of the testis. These results demonstrate that oxidative stress can directly cause germ cell apoptosis, even outside the IR model, and confirm the importance of oxidative stress in testicular IR injury. Also, following testicular IR, there is a recruitment of neutrophils and an increase in ROS production in the testis. The administration of ROS scavengers significantly reduced the IR-induced responses. Interestingly, the administration of all ROS scavengers also blocked neutrophil recruitment to the testis. The mechanism by which ROS modulates neutrophil adhesion to venules is presently under investigation, as are additional therapeutic regimens to block oxidative stress.

Animals↗

Induction of increased testis growth and sperm production in adult rats by neonatal administration of the goitrogen propylthiouracil (PTU): the critical period.

We have previously shown that treating rats with the reversible goitrogen 6-propyl-2-thiouracil (PTU) from birth to Day 25 increases testis size and sperm production in adulthood by up to 80% and 140%, respectively. The purpose of this study was to determine the critical period(s) during development when PTU treatment can increase adult testis size and sperm production. Rats were treated with PTU beginning on Days 0, 8, 16, or 24 for periods of 9, 17, or 25 days. To further define the critical period, additional rats were treated with PTU prenatally or on Days 4-24. PTU treatments of 9, 17, or 25 days beginning at birth increased testis weight 18%, 38%, and 69%, respectively, by 135 days of age, while daily sperm production (DSP) increased 35%, 65%, and 94%, respectively. Efficiency of sperm production (DSP/g testis) also increased by approximately 25% in these rats. There was an inverse relationship between testis and body weights: increasing lengths of PTU treatment increased testis weight but decreased body weight. PTU treatment starting on Day 8 or later did not increase testis weight or DSP regardless of duration. Treatment on Days 4-24 increased adult testis weight and DSP similarly to treatment from birth to Day 24, but prenatal PTU treatment was ineffective. Testosterone concentrations were not altered in treated rats, even those with increased testis weight. These results indicate that the later part of the first postnatal week (Days 4-8) is the crucial period during which PTU treatment must begin in order to increase adult testis size and sperm production.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Coincidence of counter-antigonadal and counter-antithyroid action of melatonin administration via the drinking water in male golden hamsters.

Administration of melatonin via the drinking water prevented the gonadal involution and the thyroid hormone depletion normally observed in blinded hamsters. Ten weeks after blinding male hamsters had plasma thyroxin levels that were 57% of controls and testis weights that were 8% of controls. Administration of melatonin (80 microgram melatonin/ml drinking water) to blinded hamsters restored thyroxin levels to 86% of controls and testis weights to 93% of controls. Dose response data showed that as little as 1.25 microgram (approximately 10 microgram/hamster/day) produced a significant effect on testis weight, whereas the lowest dose required to produce a significant increase in thyroxin levels was 10 microgram/ml. The coincidence of counter-antigonadal and counter-antithyroid actions of melatonin suggests a single site of action.

Animals↗

Regulation of neonatal Sertoli cell development by thyroid hormone receptor alpha1.

Neonatal hypothyroidism increases adult Sertoli cell populations by extending Sertoli cell proliferation. Conversely, hyperthyroidism induces premature cessation of Sertoli cell proliferation and stimulates maturational events like seminiferous tubule canalization. Thyroid hormone receptors alpha1 and beta1, which are commonly referred to as TRalpha1 and TRbeta1, respectively, are expressed in neonatal Sertoli cells. We determined the relative roles of TRalpha1 and TRbeta1 in the thyroid hormone effect on testicular development and Sertoli cell proliferation using Thra knockout (TRalphaKO), Thrb knockout (TRbetaKO), and wild-type (WT) mice. Triiodothyronine (T3) treatment from birth until Postnatal Day 10 reduced Sertoli cell proliferation to minimal levels in WT and TRbetaKO mice versus that in their untreated controls, whereas T3 had a diminished effect on TRalphaKO Sertoli cell proliferation. Seminiferous tubule patency and luminal diameter were increased in T3-treated WT and TRbetaKO testes. In contrast, T3 had no effect on these parameters in TRalphaKO mice. In untreated adult TRalphaKO mice, Sertoli cell number, testis weight, and daily sperm production were increased or trended toward an increase, but the increase in magnitude was smaller than that seen in WT mice following neonatal hypothyroidism. Conversely, in TRbetaKO mice, Sertoli cell number, testis weight, and daily sperm production were similar to those in untreated WT mice. In addition, Sertoli cell number and testis weight in adult WT and TRbetaKO mice showed comparable increases following hypothyroidism. Our results show that TRalphaKO mice have testicular effects similar to those seen in WT mice following neonatal hypothyroidism and that TRbetaKO mice, but not TRalphaKO mice, have normal Sertoli cell responsiveness to T3. Thus, effects of exogenous manipulation of T3 on neonatal Sertoli cell development are predominately mediated through TRalpha1.

Animals↗

Changes in gonadal weights, serum lipids, and glucose during maturation in the juvenile northern bobwhite quail (Colinus virginianus).

Changes in serum lipids, serum glucose, and gonadal development during maturation of Colinus virginianus were determined in two trials. In Trial 1, sex, BW, and serum concentrations of total cholesterol, high, low, and very low density lipoprotein cholesterol, triglycerides, and glucose were determined every 2 d from 2 to 14 d and weekly from 21 to 49 d. Relative ovary or testis weights between 14 and 49 d were determined weekly. Body weight increased and all measured serum constituents changed in males and females between 2 and 49 d; however, relative testis weight decreased between 14 and 49 d. In Trial 2, sex, BW, cholesterol, and relative ovary and testis weights were determined in birds at 56 and 63 d of age. The distinctness of external sexual phenotype and its relationship to BW, cholesterol, and relative gonadal weight were also determined at 56 and 63 d. Body weight increased and serum cholesterol decreased in both sexes between 56 and 63 d, but had no association with the distinctness of external sexual phenotype. It was concluded that the development of external sexual identity in male and female Northern Bobwhite quail prior to sexual maturity was not related to changes in BW, gonad weight, serum lipids, or serum glucose before 63 d of age.

Aging↗

Effects of pre-exposure of mouse testis with low-dose (16)O8+ ions or 60Co gamma-rays on sperm shape abnormalities, lipid peroxidation and superoxide dismutase (SOD) activity induced by subsequent high-dose irradiation.

PURPOSE: To investigate the effects of pre-exposure of mouse testis with low-doses of (16)O8+ ions or 60Co gamma-rays on sperm shape abnormalities, lipid peroxidation and superoxide dismutase (SOD) activity induced by subsequent high-dose irradiation. MATERIALS AND METHODS: Testes of the B6C3F1 hybrid strain mice were pre-irradiated with 0.05 Gy of (16)O8+ ions or 60Co gamma-rays and then after 4 h given a test irradiation with 2 Gy of the same radiation type. SOD activity and thiobarbituric acid reactive substances (TBARS) in the testes were determined by spectrophotometric and TBA methods respectively at 4 h after irradiation. Testis weight, sperm count and sperm morphology were analysed at day 35 after irradiation. RESULTS: Compared with controls, there was a significant increase in SOD activity and a significant decrease in TBARS level of pretreated testes. Testis weight loss, sperm count reduction and sperm abnormalities were significantly lower in the pretreated testes. The bioeffects of a 2 Gy dose of (16)O8+ ions relative to 60Co gamma-rays were 1.84 +/- 0.28 for testis weight, 1.22 +/- 0.25 for sperm count and 1.29 +/- 0.10 for sperm abnormalities. CONCLUSIONS: These data suggest that pre-exposure of testes with a low dose of heavy ions or gamma-rays renders the organ more resistant to subsequent high-dose irradiation. The increase of SOD activity and the decrease of lipid peroxidation levels induced by low-dose ionizing irradiation may be involved in this resistance. The effects with heavy ion irradiation were greater than with gamma-rays.

Animals↗

Endocrine and exocrine effects of testicular torsion in the prepubertal and adult rat.

Previous studies of experimental torsion have suggested that there may be important differences between the adult testis and the prepubertal testis in their responses to torsion, especially with regard to the potential for contralateral damage following unilateral testicular torsion. In the present study, adult Sprague-Dawley rats and prepubertal Sprague-Dawley rats (35 days of age) were subjected to unilateral 1-, 2-, and 4-hour periods of 720 degrees or 360 degrees testicular torsion. Ipsilateral and contralateral testes were examined 30 and 60 days after torsion repair for effects on testis weight, histology, and daily sperm production (DSP). Other animals were subjected to 1-/or 4-hour 720 degrees torsion, and testicular vein testosterone concentrations were determined 30 days later. In adult animals, 1-, 2-, and 4-hour 720 degrees torsion resulted in a significant decline in ipsilateral testis weight within 30 days. Endocrine and exocrine function were also clearly disrupted. In prepubertal animals, 1-hour 720 degrees torsion significantly reduced testis weight 60 days after surgery. Also, prepubertal DSP values and testicular vein testosterone concentrations were not significantly reduced from control values by 1-hour 720 degrees torsion when examined 30 days after surgery. Longer periods of 720 degrees torsion resulted in damage similar to that seen in the adult animals. Neither adult nor prepubertal animals regained any lost function when examined 60 days after insult. Torsion of 360 degrees induced no testicular injury in adult or prepubertal animals. Contralateral testes were not affected by degree or duration of torsion in either adult or prepubertal animals. These results suggest that the prepubertal testis may be more refractory to the effects of short periods of torsion than the adult. More importantly, these results demonstrate that ipsilateral torsion does not result in contralateral testicular damage in either adult or prepubertal animals.

Animals↗