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Testes function and feedlot performance of bulls actively immunized against gonadotropin-releasing hormone: effect of age at immunization.

Testes function, feedlot performance, and carcass traits were evaluated in bulls actively immunized against gonadotropin-releasing hormone (GnRH) at different ages. Bull calves were randomly assigned to one of seven treatment groups (n = 15 calves/group). Calves were unimmunized (Group 1), immunized at 1.5, 4, 7, or 12 mo of age with a GnRH-keyhole limpet hemocyanin (KLH) conjugate (Groups 2 to 5, respectively), or castrated at 4 mo of age (Groups 6 and 7). Immunized bulls did not receive a secondary, or booster, immunization. Calves in group 6 received Synovex-C at castration and Synovex-S at weaning and feedlot entry. Anti-GnRH titer was evident at slaughter in all immunized bulls. However, the final immune response of bulls immunized at 1.5 mo was significantly lower than the response of bulls immunized at later stages of development. Final scrotal circumference and testis weight in bulls immunized at 4, 7, or 12 mo of age were significantly reduced relative to unimmunized bulls. The final live weight, feedlot gain, and carcass weight of immunized and unimmunized bulls did not differ (P > .05) from the same parameters in steers implanted with Synovex. Longissimus muscle area, marbling score, and backfat thickness did not differ between immunized and unimmunized bulls. The sex class score of the carcasses of immunized bulls did not differ from the score of steer carcasses. In contrast, a significantly higher proportion of carcasses from unimmunized bulls graded as bullock carcasses. Taken together, these data indicate that a single immunization against GnRH at 4 to 12 mo of age results in significant attenuation of testicular growth in bulls. These data also demonstrate that immunization against GnRH reduces the masculinity of carcasses from bulls, but does not affect feedlot performance, longissimus muscle area, marbling score, or backfat thickness. These results suggest that single immunization with the GnRH-KLH conjugate may have practical utility as a noninvasive alternative to surgical castration in management of beef cattle.

Aging↗

Recent developments in the management of testicular germ cell tumors.

Testicular germ cell tumors are now generally regarded as a highly curable cancer in the majority of cases, even when patients present with advance disease. However that does not imply that researchers and clinicians have become complacent in their efforts to improve our understanding and the treatment outcome of this disease. This is an overview of recent developments in the management of testis cancer.

Germinoma↗

Thyroid function and puberty.

Thyroid hormones are essential for normal growth, sexual development and reproductive function. During puberty, changes in thyroid functions and an increase in thyroid volume occur as an adaptation to body and sexual development. Hypothyroidism diagnosed late in prepubertal years, usually due to Hashimoto's thyroiditis, can cause a delay of puberty or incomplete isosexual precocity (development of breast and internal genitalia in girls and increased testis volume in boys without adrenarche). In contrast, normal pubertal development and adequate menarche have been documented in congenital hypothyroidism detected by neonatal screening and treated early. The effect of hyperthyroidism on pubertal development is not well known, but a short period of hyperthyroidism seems not to have major negative effects. In adolescence or young adulthood, menstrual dysfunction, infertility, and stillbirth or premature birth are associated with thyroid dysfunction.

Female↗

[Fournier's gangrene: a case report].

A 40-year-old male was admitted complaining of high grade fever, pain, redness and swelling of the right scrotum, right perineum and right flank region. He had no apparent history of previous infection or diabetes mellitus. At the time of admission, the scrotum was partly necrotic with repulsive feculent pus discharge and there was crepitus on palpation of involved areas. Culture of purulent discharge yielded the growth of anaerobic organisms. Surgical drainage was performed immediately and debridement of necrotic tissue in the involved areas was often repeated. At the same time, the patient received antibiotic therapy that included agents effective against anaerobic bacteria. However, the scrotal skin developed gangrene and the right testis hung suspended with cord exposed. This testis was intact. The scrotal skin defect was cured using a skin graft, after the infection had been brought under control.

Adult↗

Intratubular malignant germ cells in testicular biopsies: clinical course and identification by staining for placental alkaline phosphatase.

This study was undertaken to determine the clinical course of patients with intratubular malignant germ cells (ITMGCs) and to evaluate the reliability of placental alkaline phosphatase (PLAP) for detection of these cells. Eight patients with ITMGCs in testicular biopsy were followed. Four patients received no further immediate treatment. Two of these showed no evidence of disease after 190 and 132 mo; one developed seminoma at 38 mo, and one developed seminoma of the contralateral testis in 61 mo. The remaining four patients underwent immediate orchiectomy. Orchiectomy findings were invasive seminoma in three testes, intratubular seminoma in one, and residual ITMGCs in one testis (one patient had bilateral orchiectomy). Also studied were two testicular biopsies from patients with known retroperitoneal germ cell tumors, respectively, seminoma and teratoma. Both had ITMGCs in their testes. Immunoperoxidase stains for PLAP gave a positive result in all biopsies showing intratubular malignant germ cells. PLAP was not demonstrated in spermatogonia in 471 control biopsies which did not show germ cell neoplasia. Two other patients with incidental seminoma on biopsy for infertility are discussed. These results show that ITMGCs show a high rate of progression to invasive disease, but can show an indolent course. PLAP is a sensitive and specific marker for ITMGC, facilitating diagnosis.

Adolescent↗

Testicular torsion: simple grading for histological evaluation of tissue damage.

Histological investigation of 63 biopsies taken during surgical detorsion of twisted testes reveals 3 morphologically different degrees of damage. In grade 1 injury the testicular parenchyma shows edema of interstice, slight blood extravasation and a desquamation of the germ cells. The grade 2 injury is characterized by a diffuse hemorrhagic saturation of the interstice and partial necrosis of germ cells. The grade 3 injury corresponds to a fully developed hemorrhagic infarction of the testis. The biopsies taken within the first 4 h after onset of symptoms show a relatively high number of minor changes (grade 1) which hold out hope for restitutio ad integrum. Grade 2 injury predominates in the period between 4 and 8 h, but it can appear also in the first 4 h. Only after 24 h all the testes examined are completely necrotic. This study shows that the amount of time that elapses between onset of symptoms and surgical detorsion is not the only factor to predict the outcome of the injured testis.

Adolescent↗

Experimental Sertoli cell tumors in the mouse and their progression into a mixed germ cell-sex cord proliferation.

Males of transgenic families where the large T protein of polyoma virus is expressed in the seminiferous epithelium of the testis (Sertoli and germ cells) develop bilateral testicular tumors when they become old (15 to 18 months). The histological features of these tumors revealed a neoplastic proliferation of Sertoli cell origin. Occasional isolated germ cells arrested at premeiotic stages were seen in the tumor. They did not participate in tumoral proliferation and their malignant character could not at first be established. Tumor cells injected in athymic (nu/nu) mice generated secondary tumors. In this case, a proliferative component of non-Sertoli origin was clearly evident. Its ultrastructural characteristics and the expression of genes that are transcribed in vivo in male germ cells (c-kit, LDH-X, and Hox a-4) suggest the progression of an initial, apparently pure Sertoli cell tumor into a mixed proliferation.

Animals↗

Etiology of benign prostatic hyperplasia.

Benign Prostatic Hyperplasia (BPH) is the most common neoplastic condition that afflicts men, and it constitutes a major factor impacting the health of the American male. This article reviews voiding dysfunction and the role of aging, the testis, and androgen in the development of BPH. Emphasis is placed on new concepts in the basic aspects of BPH etiology as a result of recent investigations.

Aging↗

Radiosensitivity of testicular cells in the fetal mouse.

The effects of prenatal X irradiation on postnatal development of the CBA/P mouse testis was studied. At days 14, 15 and 18 post coitus pregnant female mice were exposed to single doses of X rays ranging from 0.25-1.5 Gy. Higher doses resulted in extensive loss of fetal mice. In the male offspring, at days 3 and 31 post partum, the numbers of gonocytes, type A spermatogonia and Sertoli cells per testis were determined using the disector method. Furthermore, after irradiation at day 15 post coitus, the numbers of Leydig cells, mesenchymal cells, macrophages, myoid cells, lymphatic endothelial cells, endothelial cells and perivascular cells per testis were also determined at days 3 and 31 post partum. At day 3 post partum, the number of germ cells was decreased after irradiation at days 14 and 15 post coitus. A D0 value of 0.7 Gy was determined for the radiosensitivity of the gonocytes at day 14 post coitus. A D0 value of 0.8 Gy was determined for the gonocytes at day 15 post coitus which, however, seems to be less accurate. No accurate D0 value could be determined for the gonocytes at day 18 post coitus. At day 31 post partum, the repopulation of the seminiferous epithelium as well as testis weights and tubular diameters were more affected by irradiation with increasing age of the mice at the time of irradiation. The percentage of tubular cross sections showing spermatids decreased with increasing dose after irradiation at days 15 and 18 post coitus, but not after irradiation at day 14 post coitus. Furthermore, in tubular cross sections showing spermatids, exposure of testes to 1.25 and 1.5 Gy at day 18 post coitus resulted in significantly lower numbers of spermatids per cross section when compared to those testes exposed to the same doses at day 15 post coitus. This indicates that the radiosensitivity of the gonocytes increases with fetal age. Prenatal irradiation did not cause significant changes in the numbers per testis of the Sertoli cells or the interstitial cell types. The present results indicate that, in the fetal mouse testis, the spermatogonial stem cells are more sensitive to X irradiation than in the adult testis, while Sertoli cells and interstitial cells are relatively resistant.

Aging↗

Sex-specific and left-right asymmetric expression pattern of Bmp7 in the gonad of normal and sex-reversed chicken embryos.

A genetic switch determines whether the indifferent gonad develops into an ovary or a testis. In adult females of many avian species, the left ovary is functional while the right one regresses. In the embryo, bone morphogenetic proteins (BMP) mediate biological effects in many organ developments but their roles in avian sex determination and gonadal differentiation remains largely unknown. Here, we report the sex-specific and left-right (L-R) asymmetric expression pattern of Bmp7 in the chicken gonadogenesis. Bmp7 was L-R asymmetrically expressed at the beginning of genital ridge formation. After sexual differentiation occurred, sex-specific expression pattern of Bmp7 was observed in the ovary mesenchyme. In addition, ovary-specific Bmp7 expression was reduced in experimentally induced female-to-male reversal using the aromatase inhibitor (AI). These dynamic changes of expression pattern of Bmp7 in the gonad with or without AI treatment suggest that BMP may play roles in determination of L-R asymmetric development and sex-dependent differentiation in the avian gonadogenesis.

Animals↗

In vitro steroidogenesis in testes of three infants, two with ambiguous external genitalia and one with true precocious puberty: Evidence for the presence of active 17 beta-hydroxysteroid oxidoreductase in immature human testes.

The present report investigated steroidogenesis in vitro in testis tissues obtained from two boys aged 8 months and 4 years with ambiguous external genitalia and male vagina, and a 4-year-old body with true precocious puberty. Histologically, testes of the former two boys are still immature and the testis of the last one contains differentiated Sertoli cells and primary spermatocytes, but no mature Leydig cells are recognized in any of them. In each testis, 17 beta-hydroxysteroid oxidoreductase is active for androstenedione in the presence of an excess amount of NADPH, while delta 5-3 beta-hydroxysteroid dehydrogenase and delta 4-steroid 5 alpha-reductase activities are limited. 17 alpha-Hydroxylase and C17--20 lyase are significantly active in each testis and are enhanced in the testis of the boy with precocious puberty. Although the testis tissue used in the present study may not be biologically normal and the number of cases investigated is still limited, the above results indicate that active 17 beta-hydroxysteroid oxidoreductase is present in immature human testes and that delta 5-3 beta-hydroxysteroid dehydrogenase may become active in the human testis at the advanced stage of the development of testicular function during the puberty.

17-Hydroxysteroid Dehydrogenases↗

Intra-acrosomal organization of a 90-kilodalton antigen during spermiogenesis in the rat.

The localization of an acrosomal protein was studied using a monoclonal antibody MN7 raised against mouse spermatozoa. MN7 specifically recognized the anterior acrosome of several mammalian (mouse, rat, hamster) spermatozoa fixed with paraformaldehyde. An immunoblot study with periodate treatment showed that MN7 recognized a carbohydrate region of a 90 kDa protein in an extract of mouse and rat cauda epididymal spermatozoa. The change in distribution of the MN7 antigen during acrosome development was investigated in the rat testis using the pre-embedding immunoperoxidase technique. The antigen first appeared in the proacrosomic granules of spermatids in steps 1-2. Small vesicles adjacent to the outer acrosomal membrane and the developing acrosomic system were immunoreactive during steps 4-7. The majority of the antigen was then redistributed to the head-cap portion during steps 8-18, and finally restricted to the anterior acrosome in the step 19-spermatid. These results suggest that the antigen is transported to the acrosome by way of the vesicles that originate from the Golgi apparatus during early spermiogenesis, and are then delivered to the final destination within the acrosome by the intra-acrosomal migration during late spermiogenesis.

Acrosome↗

The germ cell nuclear factor mGCNF is expressed in the developing nervous system.

Using a reinoic acid receptor hybridization probe, we have isolated a mouse embryonic cDNA that encodes the germ cell nuclear factor (mGCNF). The in vitro translated protein binds specifically to the direct repeat of the sequence-AGGTCA-which is characteristic of a subclass of nuclear receptors, albeit with a spacing of zero that is unique among the receptors. Northern analysis shows embryonic expression after mouse gastrulation and during early organogenesis, as well as expression in the adult testis. The message level decreases during embryonic development. Whereas there are two transcripts in the testis, only the larger one is found in embryos. In situ analysis of embryos at days 6.5-10.5 of gestation shows that, in the early postimplantation period, high transcript levels are found in ectodermal cells and in the primitive streak. During further development the expression becomes more restricted. Mainly cells of the developing nervous system are expressing the receptor. Our findings imply that GCNF is involved in two apparently disparate developmental events.

Amino Acid Sequence↗

Photosensitive stages in pubertal development of male deer mice (Peromyscus maniculatus).

Male deer mice (Peromyscus maniculatus bairdii) were exposed to a long (15L:9D) or short (6L:18D) photoperiod during four stages of development. At 6 weeks of postnatal age degree of pubertal development was determined by measurement of testis and seminal vesicle weights and area of the androgen-dependent sebaceous gland. Continuous exposure to a short photoperiod beginning before conception (i.e. mother kept in short days), at conception, or at birth markedly retarded pubertal development. Initiation of short-day treatment after weaning at 3 weeks of age was partly effective in inhibiting puberty. Males exposed to long days beginning at weaning were stimulated fully, however, having reproductive organs as large at 6 weeks of age as those of males housed on long days for the entire experiment. These results indicate that pubertal development in male deer mice is regulated by early postnatal, but not prenatal, photoperiod. However, early after weaning, males are more responsive to increasing than to decreasing photoperiod.

Animals↗

Contiguous allografts of male and female gonadal primordia in the rat.

Male and femal gonadal primordia from fetal rats were grafted in contiguity under the kidney capsule of normal, castrated and spayed adult host rats. Irrespective of the gonadal status of the host, growth and differentiation of primary overian follicles were suppressed when a fetal testis was grafted close to a fetal ovary. Instead, cystic or tubular structures developed, some of them containing atretic ova in their lumina. The testis grafts, on the other hand, always differentiated extremely well. This is supportive evidence for the concept that the early fetal testis elaborates a substance or substances which are capable or preventing proper development of follicles in ovarian primordia trasplanted next to them.

Animals↗

Testosterone and androstenedione concentrations in human testis and epididymis during the first two years of life.

Testosterone and androstenedione were measured in testicular and epididymal tissue of 37 previously healthy infants between 1 and 24 months of age who died suddenly. In half of the patients elevated plasma levels of cortisol and androstenedione suggested preterminal stress. Plasma testosterone levels, however, did not differ from those in healthy infants. Testicular testosterone concentrations were maximal in boys from 1-3 months of age (median, 36.6 ng/g; range, 7-380 ng/g) with peak values similar to those found in pubertal or even adult testes. Thereafter testicular testosterone concentrations decreased and after the age of 6 months all values were below 12.5 ng/g, which corresponds to the low normal range of older prepubertal boys. Plasma testosterone and testicular testosterone correlated significantly (P less than 0.001). On average the testicular concentrations were 36.4 times higher than the corresponding plasma concentrations. Testicular androstenedione was low but correlated significantly with testicular testosterone (P less than 0.001). Epididymal testosterone concentrations were surprisingly high (1-3 months: median, 10.3 ng/g; range, 4-42.7 ng/g) and averaged 30% of the testicular testosterone concentration. Thus, epididymal testosterone concentrations were significantly higher than the circulating plasma testosterone levels, indicating the capacity of the infant epididymis to accumulate androgens. These findings suggest that high local testosterone concentrations during early infancy are important not only for the testis itself but particularly for the developing epididymis.

Aging↗

Analysis of fibroblast growth factor 2 (FGF2) gene transcription and protein distribution in the bovine testis.

Several fibroblast growth factors (FGFs) are implicated in proliferation and differentiation of both somatic and germ cells during testicular development, as well as in spermatogenesis of adult testis. The expression of FGF2 was studied in the adult bovine testis using quantitative RT-PCR, RNA in situ hybridization, and immunohistochemistry. Quantitative RT-PCR revealed consistent levels of FGF2 mRNA in parenchymal samples of the bovine testis. In situ hybridization localized FGF2 transcripts only in a constant fraction of Leydig and Sertoli cells as well as in modified Sertoli cells of the terminal segments. Immunohistochemistry revealed (a) no FGF2 protein in Sertoli cells (b) moderate cytoplasmic staining in Leydig cells and spermatogonia and (c) strong nuclear and faint cytoplasmic staining in myofibroblasts, in epithelial cells of straight tubules and rete testis and in blood vessels. These observations indicate a pleiotropic effect of FGF2 on the control of spermatogenesis in a paracrine and/or autocrine manner.

Animals↗

Testicular tumor after cisplatin-based chemotherapy for germ cell malignancy.

Among 417 patients treated with cisplatin-based chemotherapy for germ cell malignancy (median follow-up 7 years) we observed 6 patients who developed a second tumor of the testis. In 3 cases the first tumor was of testicular origin, whereas in the other cases the initial tumor presented in the retroperitoneal space. Although cisplatin-based chemotherapy may reduce or delay the development of a contralateral testicular tumor, the risk apparently is not completely eliminated. Patients with primary retroperitoneal germ cell tumors need a close and careful follow-up, as they appear to be at an increased risk for developing a testicular tumor.

Adult↗