Scrotal Testes Research Articles

Acute castration and/or tailing distress and its alleviation in lambs

Purposes and approach: Acute castration and/or tailing distress in lambs has been examined extensively during the last decade. At least 59 different approaches to assessing and alleviating this distress have been reported so that the literature is quite complex. The purpose of this paper is to provide an overview of the literature on castration and/or tailing distress, where the distress was assessed using acute changes in plasma cortisol concentrations. A method of analysis involving the integrated cortisol response (i.e. the areas under the cortisol curves while the plasma concentration is above pretreatment values) to each treatment and using treatments which were common to different studies as reference points, allowed meaningful comparison within and between studies. A 6-point ranking scale emerged, where rank 1 represented the least distress and rank 6 the most distress. Comparison of acute distress responses: This analysis revealed the following major points. Surgical methods of castration and/or tailing cause the greatest cortisol responses (rank 5 or 6). Most ring and ring plus clamp methods of castration plus tailing or castration, used without a local anaesthetic or systemic analgesic, cause rank 4 responses. One form of ring plus clamp castration (i.e. applying the clamp for 10 s across the full width of the scrotum distal to the ring in lambs aged no more than 1 week) reduces the cortisol response to rank 1.When these lambs are also tailed by applying a ring and clamp in a similar manner to the tail, they also exhibit a rank 1 response. Local anaesthetic given 10–20 or 1–2 min or 10–15 s before or immediately after ring only castration and/or tailing can virtually abolish the cortisol response (rank 1), depending on the site(s) of injection. For ring or ring plus clamp castration, the most effective sites (as judged by cortisol responses) are the neck of the scrotum or the testes. Delivery of local anaesthetic to achieve successful nerve blockade can be by needle, high-pressure needleless administration or, for the tail only, by an aerosol spray. Local anaesthetic injected into the scrotal neck, spermatic cords and/or testes has little effect on the overall cortisol response to clamp castration. Reductions in cortisol responses to clamp castration or to ring tailing can occur after administration of non-steroidal anti-inflammatory drugs. Most tailing methods elicit cortisol responses that are several ranks lower than those caused by castration plus tailing or castration alone. Although tailing by most methods elicits rank 1 cortisol responses, the use of local anaesthetic or non-steroidal anti-inflammatory drugs can reduce the response within the rank 1 range. Recommendation: Farmers should be encouraged to choose the lowest ranked method that is economically and practically feasible for them. Specific methods such as surgical castration should be discouraged.

Efficiency of the process of meiosis in scrotal testes of healthy boars and unilateral abdominal cryptorchid boars.

Unilateral abdominal cryptorchidism has usually been correlated with abnormalities in the spermatogenic activity of the scrotal testis. The present study describes the effects of unilateral abdominal cryptorchidism on the meiotic process in scrotal testes from postpubertal boars. The percentage of primary spermatocytes, secondary spermatocytes, and round spermatids was evaluated in testicular smears from scrotal testes of healthy boars and of right-sided unilateral abdominal cryptorchid boars. As compared to the scrotal testes of healthy boars, the scrotal testes of unilateral abdominal cryptorchid boars showed low transformation from primary to secondary spermatocytes (meiosis I), but normal transformation from secondary spermatocytes to round spermatids (meiosis II). The data obtained indicate that spontaneous unilateral abdominal cryptorchidism on the right side induced partial arrest of spermatogenesis at the primary spermatocyte stage that was attributed to anomalies in Sertoli-cell activity. Abnormal paracrine signals from altered Sertoli cells could have resulted in either disturbed mitosis, which led to the formation of spermatocytes with an abnormal DNA content, or abnormalities in the metabolic activity and the organization of the cytoskeleton of primary spermatocytes.

An unusual subset of cryptorchidism: possible end organ failure.

A paucity of germ cells exists in the cryptorchid gonad that usually correlates with a similar finding in the contralateral descended testis. However, we have noted a small number of boys with cryptorchidism in whom there is a significant difference between the histological evaluation of the cryptorchid testis and the normal descended testis that may indicate a different etiology. From 1986 to 1991, 1,426 boys with unilateral cryptorchidism underwent orchiopexy, of whom 752 also underwent bilateral testicular biopsy. Testicular volume and position, and patency of the processus vaginalis were examined. Biopsies were fixed in 2% glutaraldehyde and embedded in Epon. Semithin tissue sections were analyzed by 2 independent investigators. The number of total germ cells, gonocytes, adult dark and pale spermatogonia, primary spermatocytes and Leydig cells was assessed. Of the 1,426 boys the undescended testis was on the right side in 726 and on the left side in 658 (52 versus 48%, p = 0068). Of the 752 boys who underwent bilateral biopsy 42 (5.6%) 1.1 to 16 years old (mean age plus or minus standard deviation 0 5.2 +/- 3.65) had a poor fertility index of less than 0.2 germ cell per tubule in the cryptorchid gonad, although the germ cell count in the descended testis was normal. Of the 42 testes in this special group of boys 30 (71%) were on the right side (Fisher's exact test p <0.23), including 16 (38%) in an intra-abdominal or high canalicular position. The processus vaginalis was patent in 86% of the intra-abdominal testes and in 100% of those located at the tubercle but in only 25% of those in a pre-scrotal position. While average germ cell count in the cryptorchid testis was 0.06 per tubule with abnormal germ cell maturation, number was normal (greater than 2 germ cells per tubule) in the contralateral descended testis with a normal distribution of adult dark and pale spermatogonia, and primary spermatocytes. Average volume of the cryptorchid testis was significantly less than that of the descended testis (1.20 +/- 0.35 versus 1.60 +/- 0.68 mm.3, p <0.0001). Based on the normal scrotal testis the fertility prognosis is good in this small subgroup of boys with cryptorchidism. Rather than the usual endocrinopathy of cryptorchidism, the undescended testis in these boys may be the result of end organ failure. These patients with favorable fertility potential may be recognized only if each testis is biopsied at unilateral orchiopexy.

AN UNUSUAL SUBSET OF CRYPTORCHIDISM: POSSIBLE END ORGAN FAILURE

Purpose A paucity of germ cells exists in the cryptorchid gonad that usually correlates with a similar finding in the contralateral descended testis. However, we have noted a small number of boys with cryptorchidism in whom there is a significant difference between the histological evaluation of the cryptorchid testis and the normal descended testis that may indicate a different etiology. Materials and Methods From 1986 to 1991, 1,426 boys with unilateral cryptorchidism underwent orchiopexy, of whom 752 also underwent bilateral testicular biopsy. Testicular volume and position, and patency of the processus vaginalis were examined. Biopsies were fixed in 2% glutaraldehyde and embedded in Epon. Semithin tissue sections were analyzed by 2 independent investigators. The number of total germ cells, gonocytes, adult dark and pale spermatogonia, primary spermatocytes and Leydig cells was assessed. Results Of the 1,426 boys the undescended testis was on the right side in 726 and on the left side in 658 (52 versus 48%, p = 0068). Of the 752 boys who underwent bilateral biopsy 42 (5.6%) 1.1 to 16 years old (mean age plus or minus standard deviation 0 5.2 +/- 3.65) had a poor fertility index of less than 0.2 germ cell per tubule in the cryptorchid gonad, although the germ cell count in the descended testis was normal. Of the 42 testes in this special group of boys 30 (71%) were on the right side (Fisher's exact test p <0.23), including 16 (38%) in an intra-abdominal or high canalicular position. The processus vaginalis was patent in 86% of the intra-abdominal testes and in 100% of those located at the tubercle but in only 25% of those in a pre-scrotal position. While average germ cell count in the cryptorchid testis was 0.6 per tubule with abnormal germ cell maturation, number was normal (greater than 2 germ cells per tubule) in the contralateral descended testis with a normal distribution of adult dark and pale spermatogonia, and primary spermatocytes. Average volume of the cryptorchid testis was significantly less than that of the descended testis (1.20 +/- 0.35 versus 1.60 +/- 0.68 mm. 3, p <0.0001). Conclusions Based on the normal scrotal testis the fertility prognosis is good in this small subgroup of boys with cryptorchidism. Rather than the usual endocrinopathy of cryptorchidism, the undescended testis in these boys may be the result of end organ failure. These patients with favorable fertility potential may be recognized only if each testis is biopsied at unilateral orchiopexy.

P-008. Lectin affinity of the lamina propria, peritubular cells and Sertoli cells in scrotal and abdominal testes of boars

P-008. Lectin affinity of the lamina propria, peritubular cells and Sertoli cells in scrotal and abdominal testes of boars

Cloning of Novel Temperature-Related Expressed Sequence Tags in Rat Testis during Spermatogenesis

Spermatogenesis needs the relatively cool environment of the scrotum in most mammals, it would be arrested when the testis was exposed to abdominal temperature. In this study, we have used a differential display PCR technique (DD-PCR) to screen temperature-related ESTs during spermatogenesis (TRS) in scrotal testes through a unilateral cryptorchid rat model afterin situanalysis of testis cell DNA fragmentation. We reported here the cloning and sequencing of three such ESTs: TRS1, TRS3, and TRS4. Northern blot analysis confirmed that they were expressed specifically in scrotal testes.In situhybridization showed that TRS1 was mainly expressed in the spermatocytes and the round spermatids in scrotal testis. Homology searches revealed that TRS1 and TRS3 were unknown cDNA sequences, and TRS4 was identical to a known EST whose function had not been reported. TRS1, TRS2, and TRS3 were first found to be temperature-related during spermatogenesis.

Experimental cryptorchidism induces a change in the pattern of expression of LH receptor mRNA in rat testis after selective Leydig cell destruction by ethylene dimethane sulfonate.

In the rat, the cytotoxic drug ethylene dimethane sulfonate (EDS) selectively eliminates mature Leydig cells (LCs) from testicular interstitium, activating a complex process of proliferation and differentiation of pre-existing LC precursors. We observed previously that after EDS treatment, the early LC precursors persistently express a truncated 1.8 kb form of LH receptor (LHR) mRNA. This prompted us to study whether experimental cryptorchidism, known to alter the process of LC repopulation, can influence the pattern of testicular LHR mRNA expression after EDS administration. EDS treatment completely eliminated mature LCs both in control and unilaterally cryptorchid (UC) rats. This response was followed by gradual reappearance of newly formed, functionally active LCs, as evidenced by the recovery in testicular LHR content and plasma testosterone levels in both experimental groups. Noteworthy, the rate of LC repopulation was higher in the abdominal testes of UC rats, in keeping with previous findings. Interestingly, the 1.8 kb LHR transcript was persistently expressed in scrotal testes at all time-points, but undetectable upon Northern hybridization in abdominal testes at early stages after EDS administration, when low levels of expression of truncated LHR transcripts could only be detected by semi-quantitative RT-PCR analysis. In addition, the faster LC repopulation in cryptorchid testes was associated with precocious recovery of the complete array of LHR mRNA transcripts, including the 1.8 kb species. These changes appeared acutely and irreversibly, as unilateral positioning of scrotal testes into the abdomen resulted in a rapid loss of expression of the 1.8 kb LHR transcript, whereas scrotal relocation of the UC testes failed to alter the pattern of LHR gene expression. In conclusion, experimental cryptorchidism changes the pattern of LHR mRNA expression in rat testis after selective LC destruction by EDS. This change, i.e. repression of the 1.8 kb LHR transcript after EDS administration, is acute and irreversible, and likely related to the impairment of testicular microenvironment following cryptorchidism. However, even though at low levels, the expression of truncated forms of LHR mRNA appears to be a universal feature of proliferating LC precursors. The UC testis may represent a good model for analysis of the regulatory signals involved in the control of LHR gene expression.

Characterization of the semen quality of postpuberal boars with spontaneous unilateral abdominal cryptorchidism on the right side.

In recent studies, we found that the ectopic testis from postpuberal boars with unilateral abdominal cryptorchidism does not produce sperm. Therefore, in these males, the seminal characteristics can be used as indicators of the activity of the scrotal testis and its epididymis and also the accessory glands. The semen quality (ejaculate volume, cell-rich fraction volume, sperm concentration, sperm vitality, sperm motility, sperm morphology and cephalic stability of spermatozoa) was evaluated in healthy postpuberal boars and in postpuberal boars with unilateral abdominal cryptorchidism on the right side. In comparison with the healthy boars, the unilateral abdominal cryptorchid boars showed a significant decrease of the ejaculate volume, sperm concentration and sperm motility. The low sperm concentration indicated that unilateral abdominal cryptorchidism severely impairs the sperm production of the scrotal testis. The decrease of ejaculate volume was attributed to an abnormal activity of the accessory glands. The alterations in sperm motility develop as a result of dysfunctions in the epididymal epithelium and/or the accessory glands. The sperm vitality, sperm morphology and cephalic stability of spermatozoa maintained normal values; therefore, at testicular level, despite the low sperm production, the germ cell differentiation is not disturbed. At epididymal level, the morphological maturation of spermatozoa is not altered.

Morphologic study of the testes from spontaneous unilateral and bilateral abdominal cryptorchid boars.

Macroscopical and histological characteristics were examined in both testes from three healthy boars, three boars with unilateral abdominal cryptorchidism on the right side, and three boars with bilateral abdominal cryptorchidism. Abdominal cryptorchidism, unilateral and bilateral, provoked a significant decrease of the weight and volume of the ectopic testes. The scrotal testis of the unilateral cryptorchid boars showed an increase in its volume and weight. Cryptorchidism also induced abnormalities in the histological structure of seminiferous tubules, lamina propria, and interstitial tissue of the abdominal testes. The number of seminiferous tubules decreased; the seminiferous epithelium was constituted by few spermatogonia with an atypical pattern and by abnormal Sertoli cells. The lamina propria showed a variable degree of thickening and collagenization. The interstitial tissue was very developed but displayed a decrease in the Leydig cell population. These abnormalities were more critical in bilateral cryptorchidism than in unilateral cryptorchidism. The scrotal testis of the unilateral cryptorchid boars showed normal appearance, but a decrease of the number of seminiferous tubules was observed. Moreover, the seminiferous tubules showed impaired spermatid maturation. The alterations observed in the abdominal testes of the unilateral and bilateral cryptorchid boars were attributed to defective proliferation and differentiation of Sertoli cells and Leydig cells. The anomalies in the scrotal testis of the unilateral cryptorchid boars were due to disturbances in the Sertoli cell activity.

Could testicular descent in humans be promoted by direct androgen stimulation of the gubernaculum testis?

Gubernaculum testis and androgens play an important role in physiologic testicular descent. A direct androgen stimulation of the gubernaculum is only possible in the presence of specific receptors, which have not yet been demonstrated. We have determined the androgen-binding capacity in 61 samples of gubernaculum testis from 48 patients, 34 samples belonging to patients with maldescended testes. In 43 out of 61 instances we found androgen binding with values up to 72 fmol/mg, with a mean of 13.08 fmol/mg. In 27 samples from patients with a deep scrotal positioned gonad the mean androgen-binding capacity was 18.74 fmol/mg. In 10 samples from patients with a gonad in the proximal scrotum and 19 patients with epifascial ectopy or a low inguinal position the mean androgen-binding capacities decreased progressively to 9 fmol/mg and 5.95 fmol/mg. In the 5 samples from patients with high inguinal or abdominal testes the binding capacity of 17.8 fmol/mg did not significantly differ from the value obtained in the samples of the normal-positioned gonads, suggesting that transabdominal descent is probably not androgen-dependent. We divided the probes into receptor status positive for a binding capacity higher than or equal to 10 fmol/mg, and receptor status negative for a binding capacity under 10 fmol/mg. 63% of the samples from patients with scrotal positioned testes were receptor status positive, 85% of the samples belonging to patients with maldescended testes were receptor status negative. Receptor status was negative in patients with high scrotal, epifascial or low inguinal and high inguinal or abdominal testes in 90%, 95% and 40% of the samples respectively. Immunohistochemical examination of 10 samples showed small cell groups with stained nuclei in 2 out of 5 patients with normal-positioned testes. All other samples were negative. These findings prove that hormone binding was accomplished by specific intranuclear receptors. These findings allow for the first time the hypothesis of a direct androgen stimulation of the human gubernaculum testis. The probable mechanism is an increase in mucopolysaccharides leading to a swelling of the gubernaculum, dilating the inguinal canal and promoting testicular descent. Although certainly a multifactorial process, quality and quantity of androgen receptors would influence the extent of transinguinal testicular descent.

Does proximal genitofemoral nerve division induce testicular maldescent or ascent in the rat?

To investigate whether the division of the proximal genitofemoral nerve (GFN) in neonatal rats induces testicular undescent or ascent in adulthood. Neonatal Wistar King A rats underwent a unilateral proximal GFN transection on either the right or left side. At the age of 30 days, testicular descent was examined in all rats and the position of the testis recorded. The animals were allowed to develop further and the position of the testis re-examined at the age of 90-180 days, when the testes were removed and weighed. Sham-operated rats were used as controls. At the age of 30 days, four of the 46 (9%) operated rats showed a unilateral undescended testis on the operated side. At the age of 90-180 days, 43 rats were re-examined (three rats died before re-examination); 34 (79%) of these rats showed undescended testes on the operated side. The occurrence of cryptorchidism was significantly higher in the 90-180-day-old mature rats than in 30-day-old prepubertal rats (P<0.01). The mean (sd) weight of the undescended testes, at 2.36 (0.21) mg/g body weight, was significantly less than that of the contralateral scrotal testes, at 3.83 (0.23) mg/g; P<0.01) and of the control testes at the age of 90-180 days. In the sham-operated rats, all testes were located at the bottom of the scrotum at 30 days of age and no rats showed any testicular ascent thereafter. The proximal division of the GFN in neonatal rats not only causes inguinoscrotal testicular maldescent but may also induce testicular ascent in adulthood. Testicular ascent may thus be caused by some intrauterine disorders of the GFN in patients with ascending testis.

Germ-cell degeneration in experimental unilateral cryptorchidism: role of apoptosis

We investigated the possible involvement of apoptosis in the increased germ-cell degeneration in undescended testes (UDT). Experimental unilateral cryptorchidism was induced in 21-day-old rats, and both testes were removed for in-situ TUNEL staining of apoptotic cells at 1, 3, 7, 10, and 14 days postoperation. A gradual increase in the incidence of apoptosis was seen at 21-28 days of age in the control testes, followed by a decrease thereafter. After 10 days postoperation, the weight of the UDT was significantly lower than that of the contralateral descended testis (CDT) and the controls. However, the weight of scrotal testes in each group was similar. UDTs demonstrated a markedly increased incidence of apoptosis. By 7 days postoperation, the percentage of seminiferous tubules containing apoptotic germ cells significantly increased in UDTs compared with that in CDTs and controls (P < 0.001). Moreover, there was a significant difference in the percentage of seminiferous tubules containing apoptotic germ cells between CDTs and controls (P < 0.01). In addition, an increased incidence of seminiferous tubules containing 8-10 and >10 apoptotic germ cells from 7, 10, and 14 days postoperation in UDTs was detected. In-situ TUNEL analysis demonstrated spermatocytes to be the main type of germ cells affected in all groups. These findings suggest that spermatogenesis decreases not only in the UDT, but also in the CDT, and that the germ-cell degeneration in cryptorchidism took the form of apoptosis.

Fertility and histological studies of the contralateral testes in two different intra- and extra-abdominal rat models of unilateral cryptorchidism.

To investigate the effect of location of the testis on both testicular development and fertility in unilateral cryptorchidism. Forty-nine Wistar King A newborn male rats were divided into three groups. In group 1 (15 rats) intra-abdominal unilateral cryptorchidism were created by the intra-abdominal fixation of the testis in the neonatal period. In group 2 (16 rats) extra-abdominal unilateral cryptorchidism was created by extra-abdominal fixation of the gubernaculum in the neonatal period. In group 3, 18 rats underwent a sham operation as controls. At 90 days of age, fertility was then assessed in each rat by housing it with two mature virgin females for 2 weeks. Thereafter, at 115-120 days of age, the rats were killed and their testes removed for histological examination. There was no significant difference in the pregnancy rate between females coupled with rats from any group, but the mean number of offspring was significantly lower in females coupled with rats in group 1 than in group 2. Furthermore, histological examination of both the cryptorchid and contralateral scrotal testes showed more severe changes in the intra-abdominal than the extra-abdominal testes. These results suggest that intra-abdominal cryptorchid testes are significantly more impaired than extra-abdominal cryptorchid testes, and that such impairment might be caused by exposure of the testis to a higher temperature. The more severely impaired undescended testes may thus induce the degeneration of the contralateral scrotal testis and thereby cause subfertility in the intra-abdominal unilateral cryptorchid rat model.

A reliable endocrine test with human menopausal gonadotropins for diagnosis of true hermaphroditism in early infancy.

In true hermaphroditism diverse phenotypes and karyotypes are found; there are no distinctive laboratory features that can distinguish it from other intersex disorders, thus the diagnosis is made by the histological findings. Existence of Leydig cells is demonstrated by testosterone levels above the female range; however, presence of ovarian tissue cannot be ascertained because of the absence of a reliable functional test. Unless appropriate biopsies are performed or the whole gonad is removed, there is a risk of not diagnosing true hermaphroditism. To find a reliable test that can differentiate patients with true hermaphroditism from those with other intersex disorders, we investigated the estradiol (E2) response to human menopausal gonadotropins (hMG) in infants with genital ambiguity. These results were correlated with the histological findings. Eleven infants with genital ambiguity and four with a high scrotal testis were stimulated every 12 h with 2 IU/kg hMG. If E2 rose above 80 pg/mL (cut-off point), the test was discontinued; if after 7 days E2 remained below 80 pg/mL, the hMG dose was doubled and stimulation extended for 7 additional days. In five patients in whom true hermaphroditism was later histologically demonstrated, E2 rose above 80 pg/mL. In two of them, ovarian tissue was removed and hMG stimulation repeated; no response above our cut-off point was observed during the second test. The maximal E2 response to hMG in the remaining 10 individuals was 43 pg/mL; after laparotomy or gonadal biopsies no ovarian tissue was found. The hMG stimulation test can be considered a reliable and safe dynamic procedure for demonstrating the presence or absence of ovarian tissue in infants with genital ambiguity.

Fertility and histological studies in a unilateral cryptorchid rat model during early and late adulthood.

To investigate the effect of age on fertility and testicular development in rats with untreated unilateral undescended testes. Newborn male Wistar King-A rats were divided into two groups. In group 1, a mechanical model of unilateral undescended testis was created by performing extra-abdominal fixation of the gubernaculum in the neonatal period, and in group 2, sham-operated rats were used as controls. At 90 days old (early adulthood), the fertility of both groups was assessed by mating the rats with mature virgin females for 2 weeks. Thereafter, some of the rats were killed and their testes examined histologically, while the remaining rats were allowed to develop further. At the age of 180 days (late adulthood), fertility was re-assessed in the same way. All the rats were then killed and their testes removed for histological examination. There was no significant difference in pregnancy rate of females mated with males from either group in early adulthood. However, in late adulthood there was a significant reduction in pregnancy rate in females coupled with cryptorchid rats compared with that of females coupled with control rats. There was a significant degeneration of the unilateral cryptorchid testes compared with control testes in both early and late adulthood. In contrast, there were no significant changes in histological development between the contralateral scrotal testes and the controls in early adulthood, although they were significantly different from the controls in late adulthood. These results suggest that fertility is affected by ageing in untreated unilateral cryptorchidism; this may be induced by extensive damage not only in the undescended testes, but also in the contralateral scrotal testis, in this mechanically induced model of unilateral cryptorchidism.

Local regulation of macrophage subsets in the adult rat testis: examination of the roles of the seminiferous tubules, testosterone, and macrophage-migration inhibitory factor.

In the adult rat testis, macrophages belong to one of two subsets differentiated by expression or lack of expression of the resident macrophage surface antigen recognized by monoclonal antibody ED2. Local regulation of the testicular macrophage subsets was investigated in normal and 4-wk experimentally cryptorchid adult rats with and without s.c. testosterone implants (T-implants). Macrophage subsets ED2(+) (resident-type) and ED2(-) (monocyte-like) were identified immunohistochemically and counted in perfusion-fixed frozen testis sections. Depletion of the spermatogenic cells by cryptorchidism had no effect on testicular macrophage numbers. Inhibition of Leydig cell and seminiferous tubule function by low-dose (3 cm) T-implants caused a 40% reduction in ED2(+) resident macrophages in both scrotal and abdominal testes. High-dose (24 cm) T-implants, which inhibit Leydig cell function while maintaining normal seminiferous tubule function, also reduced the number of resident macrophages by approximately 40%, although this reduction was at least partially prevented in the abdominal testes. In the scrotal testis only, the ED2(-) monocyte/macrophage subset was significantly reduced in number by low-dose, but not high-dose, T-implants. The concentration of the Leydig cell-secreted cytokine macrophage-migration inhibitory factor (MIF) in testicular fluid was reduced by cryptorchidism, but not by the T-implants. When data from all experimental groups were combined, ED2(+) resident macrophage numbers showed a significant positive correlation with parameters of Leydig cell function (serum LH and testicular testosterone levels) but a negative correlation with MIF levels. This study indicates that Leydig cells regulate testicular macrophage numbers directly, rather than via an effect upon the seminiferous epithelium, in the adult rat testis. The data also suggest that testosterone and MIF play only a minor role, if any, in this regulation.

Changes in the Expression Pattern of Luteinizing Hormone Receptor mRNA in Rat Testis during Degeneration of Seminiferous Epithelium

Abstract Previously we reported that the experimental unilateral cryptorchidism altered the expression pattern of LH receptor mRNA in abdominal testis. To clarify whether the change was due to exposure of Leydig cells to high temperature in the abdomen, we examined the effect of unilateral efferent duct ligation on the expression. Two weeks after the operation, a relatively decreased expression of 1.8 kb transcript, increased expression of other transcripts, and degeneration of germ cells were observed in the efferent duct-ligated testes. As these changes were similar to those seen in abdominal testes of cryptorchid rats, exposure of Leydig cells to high temperature was not responsible for the changes in expression pattern of LH receptor mRNA. To examine the correlation between the changes in the receptor mRNA expression and the degeneration of seminiferous epithelium, expression of the mRNA was analyzed in unilaterally cryptorchid rats for 28 days after the operation. In scrotal testes which showed no hi...

EFFECT OF CRYPTORCHIDISM ON TESTICULAR HISTOLOGY IN A NATURALLY CRYPTORCHID ANIMAL MODEL

Purpose To determine the effect of naturally occurring cryptorchidism on testicular histology in both the cryptorchid and normally descended testis from birth to adulthood using the LE/ORL rat model. Materials and Methods Testicular histology was assessed using established morphometric measures in bilaterally descended (BD), unilaterally descended (UD), bilaterally cryptorchid (BC) and unilaterally cryptorchid (UC) testis at days 15, 22, 30, 45 and 60 of age. Testicular mass was also measured at these times. Results Changes in testicular histology in the BC and UC testes were not noted on or prior to day 30 of age. Significant changes were noted by day 45 of age and continued into adulthood at day 60 of age. There were no histological abnormalities noted in the UD and BD groups. Conclusions Since histological changes seen in this animal model occur after the time of testicular descent (day 28 of age), we hypothesize that these changes are due to an abnormal anatomical position of the testis as opposed to an inherent testicular defect in the LE/ORL rat. This hypothesis is supported by the fact that no histological differences were noted between the scrotal testes of unilaterally cryptorchid animals and bilaterally descended control animals.

Germ cell apoptosis after treatment of cryptorchidism with human chorionic gonadotropin is associated with impaired reproductive function in the adult.

Cryptorchidism results in impaired fertility. Reduced numbers of testicular germ cells can be shown histologically during the first years of life. The process causing germ cell loss in cryptorchid prepubertal boys is unknown, but it could be the result of a form of programmed cell death known as apoptosis. 25 adult men with a history of surgically treated cryptorchidism were studied, 15 of whom had received an unsuccessful human chorionic gonadotropin (hCG) therapy before orchidopexy. Apoptotic DNA fragmentation was assayed in testis biopsies taken during orchidopexy by end-labeling, both in extracted DNA and histochemically in situ. Only a few scattered apoptotic spermatogonias were seen by end-labeling of biopsies from patients not treated with hCG, whereas more extensive labeling of spermatogonia was seen after hCG treatment. As estimated by gel electrophoresis, the amount of low molecular weight DNA was 4.3-fold higher in the hCG-treated group when compared with the level in scrotal testis of non-hCG-treated patients (P < 0.001). About 20 yr after the biopsy, the low molecular weight DNA fragmentation correlated negatively with the testis volume (r = -0.84; P < 0.001) and positively with serum FSH levels (r = 0.73; P < 0.001). Findings in the semen analysis were similar between the groups. Apoptotic loss of spermatogonia after hCG treatment of cryptorchidism warrants reevaluation of the safety of this treatment.

Persistent mullerian duct syndrome with or without transverse testicular ectopia and testis tumours: F. Berkmen. Br J Urol 79:122–126, (January), 1997

Objective To report three patients with persistent Mullerian duct syndrome (PMDS) associated with a unilateral testicular tumour. Patients and methods Three adults with PMDS and an associated testicular malignancy were evaluated using physical examination, imaging, measurement of tumour markers, surgical exploration and chromosome analysis. Results The position of the uterus and fallopian tubes differed in all patients; one was in the scrotal sac, another in the abdomen and the third in the left inguinal canal. Two of the patients were cousins and their pedigree showed that they were probably in a sex-limited group. Both also had transverse testicular ectopia; fertility was documented in the younger patient. In all cases, the karyotype was proved to be 46, XY. Conclusion We recommend that the diagnosis of PMDS is made radiologically and that the detection of Mullerian inhibiting factor is mandatory. As malignancy does not occur in the retained Mullerian ducts, hysterectomy should not be performed at abdominal exploration, although orchidectomy should be, because orchidopexy offers only limited protection against future malignancy if performed after 2 years of age. It is not necessary to perform testicular biopsy to detect tumour in the scrotal testis in this syndrome, because an impalpable tumour can be localized by ultrasonography.