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PubMed1981

The ontogeny of Mullerian inhibiting substance in the gonads of the chicken.

Mullerian inhibiting substance (MIS) was studied in the testis, ovary, and ovotestis of the domestic fowl, from early embryonic development to adulthood by a graded organ-culture method using the urogenital ridge of a 14.5 day fetal rat. The chick testis had high levels of MIS from 8 days of embryonic development (4-5+) until sexual maturity, when activity declined (2+) but persisted throughout adulthood. The right gonad (ovotestis) of the hen showed moderate levels of MIS activity from 8 to 12 days of embryonic life (1-3+) before its normal involution by the time of hatching (21 days). The left gonad (ovary) of the hen also produced MIS at levels similar to that seen in the testis. Activity was high during embryonic development (4+) and after hatching, and persisted in the adult hen at diminished levels (2+). MIS production by the female gonads explains regression of the right Mullerian duct, but the mechanisms that allow preservation of the left duct remain unexplained. Evidence suggests that ovarian estrogens may interact with MIS at the receptor level to protect the left Mullerian duct. MIS persists in the sexually mature gonads of both the hen and cockeral, long after the Mullerian duct has regressed, suggesting a wider role for this substance in reproductive physiology.

Age Factors↗
PubMed1995

Xp duplications and sex reversal.

Male to female sex reversal has been observed in individuals with duplications of the short arm of the X chromosome. The study of Xp duplicated patients demonstrated that sex reversal results from the presence of two active copies of the DSS (dosage sensitive sex reversal) locus. A double dosage of DSS disrupts testis formation whereas its absence is compatible with a male phenotype, suggesting a role for DSS in ovarian development and as a link between ovary and testis formation. DSS was localized to a 160 kb region of Xp21, overlapping the adrenal hypoplasia congenita locus. The search for expressed sequences in the DSS critical region led to the identification of two types of genes: the DAM family and DAX-1, an atypical member of the nuclear receptor superfamily. Although no function is currently known for DAM genes, functional deficiency for DAX-1 has been shown to be responsible for adrenal hypoplasia congenita and hypogonadotropic hypogonadism. The search for the DSS gene(s) is still open and both the DAM genes and DAX-1 represent DSS candidate genes.

Adrenal Insufficiency↗
PubMed2004

The role of tumor necrosis factor-alpha and interleukin-1 in the mammalian testis and their involvement in testicular torsion and autoimmune orchitis.

This review will focus the roles of TNF-alpha, IL-1 alpha, and IL-1 beta in the mammalian testis and in two testicular pathologies, testicular torsion and orchitis. TNF alpha in the testis is produced by round spermatids, pachytene spermatocytes, and testicular macrophages. The type 1 TNF receptor has been found on Sertoli and Leydig cells and numerous studies suggest a paracrine mode of action for TNF alpha in the normal testis. IL-1 alpha has been reported to be produced by Sertoli cells, testicular macrophages, and possibly postmeiotic germ cells. IL-1 receptors have been reported on Sertoli cells, Leydig cells, testicular macrophages, and germ cells suggesting both autocrine and paracrine functions. While these proinflammatory cytokines have important roles in normal testicular homeostasis, an elevation of their expression can lead to testicular dysfunctions. Testicular torsion is a clinical pathology with results in testicular ischemia and surgical intervention is often required for reperfusion. A pivotal role for IL-1beta in the pathology of testicular torsion has been recently described whereby an increase in IL-1beta production after reperfusion of the testis is correlated with the activation of the stress-related kinase, c-jun N-terminal kinase, and ultimately resulting in neutrophil recruitment to the testis and germ cell apoptosis. In autoimmune orchitis, on the other hand, TNF alpha produced by T-lymphocytes and macrophages of the testis has been implicated in the development and progression of the disease. Thus, both proinflammatory cytokines, TNF alpha and IL-1, have significant roles in normal testicular functions as well as in certain testicular pathologies.

Animals↗
PubMed2000

Xanthogranulomatous funiculitis and epididymo-orchitis in a tetraplegic patient.

STUDY DESIGN: A case report of xanthogranulomatous funiculitis and epididymo-orchitis. Xanthogranulomatous inflammation is an uncommon, non-neoplastic process characterised by destruction of tissue, which is replaced by a striking cellular infiltrate of lipid-laden macrophages. CASE REPORT: A 21-year male sustained complete tetraplegia at C-6 level, after a fall in 1998. The neuropathic bladder was managed with an indwelling urethral catheter. He had many unsuccessful trials of micturition. Sixteen months after the cervical injury, he noticed swelling of the left side of the scrotum following removal of a blocked catheter. He was prescribed antibacterial therapy. Four weeks later, physical examination revealed a hard and irregular swelling encompassing the testis, epididymis and spermatic cord. The clinical diagnosis was epididymo-orchitis progressing to pyocele. Through a scrotal incision, the swollen testis, epididymis and diseased segment of the spermatic cord were removed en masse. Histopathology showed extensive areas of necrosis, with xanthogranulomatous inflammation in the spermatic cord and to a lesser extent in the testis/epididymis. CONCLUSION: Repeated episodes of high-pressure urinary reflux along the vas deferens during dyssynergic voiding, and subsequent interstitial extravasation of urine together with chronic, low-grade, suppurative infection possibly led to development of xanthogranulomatous inflammation in the testis and the epididymis. Since tissue destruction is a feature of xanthogranulomatous inflammation, the definite and curative treatment is either complete (or, where applicable, partial) excision of the affected organ in most of the cases.

Adult↗
PubMed2001

Testis ecdysiotropin, an insect gonadotropin that induces synthesis of ecdysteroid.

Testes of lepidoptera synthesized ecdysteroid in a somewhat different temporal pattern than the prothoracic glands that release ecdysteroid to the hemolymph. Brain extracts from Heliothis virescens and Lymantria dispar induced testes to synthesize ecdysteroid, but did not affect prothoracic glands. The testis ecdysiotropin (LTE) was isolated from L. dispar pupal brains by a series of high-pressure chromatography steps. Its sequence was Ile-Ser-Asp-Phe-Asp-Glu-Tyr-Glu-Pro-Leu-Asn-Asp-Ala-Asp-Asn-Asn-Glu-Val-Leu-Asp-Phe-OH, of molecular mass 2,473 Daltons. The predominant signaling pathway for LTE was via G(i) protein, IP3, diacylglycerol and PKC; a modulating pathway, apparently mediated by an angiotensin II-like peptide, was controlled via G(s) protein, cAMP, and PKA. Testis ecdysteroid caused isolated testis sheaths to also synthesize a growth factor that induced development of the male genital tract. The growth factor appeared to be a glycoprotein similar to vertebrate alpha-1-glycoprotein. A polyclonal antibody to LTE indicated LTE-like peptide in L. dispar brain medial neurosecretory cells, the suboesophageal, and other ganglia, and also in its target organ, the testis sheath. LTE immunoreactivity was also seen in testis sheaths of Rhodnius prolixus. LTE-like immunoactivity was also detected in developing optic lobes, antennae, frontal ganglia, and elongating spermatids of developing L. dispar pupae. This may indicate that LTE has a role in development as well as stimulation of testis ecdysteroid synthesis. Published 2001 Wiley-Liss, Inc.

Amino Acid Sequence↗
PubMed1989

Local control mechanisms in the testis.

The gonads are unique organs in that they harbor the cells of the germline and consequently provide the local environment necessary for the normal development and differentiation of gametes. Since the local requirements for germ differentiation differ considerably from those of somatic cells the structural and physiological organization of the gonad is complex and compartmentalized. An elaborate network of local paracrine interactions between the somatic and gametogenic elements appears to be essential for normal germ cell development in mammals. This is especially true for the testis where meiosis is continuous throughout adulthood and where the spermatogenic cycle of the seminiferous epithelium is strictly controlled in time and space. The present paper reviews briefly the rapidly expanding field of testicular paracrinology. Special emphasis is given to the role of intra- and intercompartmental paracrine communication in the development of the male gamete.

Animals↗
PubMed2005

Endogenous estrogens inhibit mouse fetal Leydig cell development via estrogen receptor alpha.

It is now accepted that estrogens play a role in male fertility and that exposure to exogenous estrogens during fetal/neonatal life can lead to reproductive disorders in the male. However, the estrogen receptor (ER)-mediated processes involved in the regulation of male reproduction during fetal and neonatal development are still largely unclear. We previously reported that ER beta deficiency affects gametogenesis in mice but changes neither the number nor the differentiated functions of fetal Leydig cells. We show here that ER alpha-deficient mice (ER alpha-/-) display higher levels of testicular testosterone secretion than wild-type mice from fetal d 13.5 onwards. This results from higher levels of steroidogenic activity per fetal Leydig cell, as indicated by the hypertrophy of these cells and the higher levels of mRNA for StAR, P450c17 and P450scc in the testis, for a similar number of Leydig cells. Because LH is not produced on fetal d 13.5 and because no change in plasma LH concentration was observed in 2-d-old ER alpha-deficient mice, LH is probably not involved in the effects of estrogens on testicular steroidogenesis in fetal and early neonatal Leydig cells. Furthermore, inactivation of ER beta did not change the effect of ER alpha inactivation on steroidogenesis. Lastly, in an organ culture system, 1 mum diethylstilbestrol decreased the testosterone secretion of wild-type fetal and neonatal testes but not of ER alpha-/- testes. Thus, this study shows that endogenous estrogens physiologically inhibit steroidogenesis via ER alpha by acting directly on the testis early in fetal and neonatal development.

Animals↗
PubMed2003

Seminiferous tubule cannulation (STC): a new, sensitive technique for detecting gene transfer in developing sperm.

As gene therapy vectors, strategies, and disease targets continue to expand and diversify, the likelihood that developing germ cells will be exposed to gene transfer vectors increases. Insertion of exogenous genetic material into the germ line might have devastating effects on normal development which could be heritable. Accordingly, it is important that vectors be tested for their potential to insert genes into developing gametes. Such tests are most difficult in males, where differentiating sperm are sequestered behind the blood-testis barrier. In this communication we report the development of a new technique, which we call seminiferous tubule cannulation (STC). We demonstrate that STC allows delivery of high quantities of gene therapy vector directly to spermatogenic cells without significantly disturbing the cytoarchitecture of the seminiferous tubule. To demonstrate the effectiveness of this technique, three promoters driving lacZ gene expression in adenovirus vectors were tested for their ability to transduce cells within the seminiferous tubule. Results indicate that the cytomegalovirus promoter, but not the Rous sarcoma virus or elongation factor 1alpha promoters, is active within the seminiferous tubule. Further development of this technique promises to lead to a standardized test for male germ cell transduction by gene therapy vectors.

Adenoviridae↗
PubMed2006

Development and optimization of a Q-RT PCR method to quantify CYP19 mRNA expression in testis of male adult Xenopus laevis: comparisons with aromatase enzyme activity.

Due to limitations of the currently used enzymatic assays, it is difficult to determine aromatase activity in testicular tissue of amphibians. Quantitative reverse transcription polymerase chain reaction (Q-RT PCR) is a sensitive and reliable technique to detect low amounts of mRNA for specific genes. This study was designed to develop and optimize a SYBR Green I-based Q-RT PCR method to quantify CYP19 mRNA in testicular tissue from male Xenopus laevis. Four quantification methods for measuring CYP19 mRNA expression were compared. The established test system proved to be highly sensitive (detectable mRNA copies < 10), reproducible (interassay CV < 5.4%, intraassay CV < 0.9%), precise and specific for the CYP19 gene. To confirm the validity of the applied test system, an ex vivo testicular and ovarian explant study with a known inducer of aromatase, forskolin, was conducted. Forskolin induced CYP19 gene expression in both ovarian (3.7-fold) and testicular (2.6-fold) explants. Of the four quantification methods, the absolute standard curve and the comparative CT method appear to be optimal as indicated by their highly significant correlation (r2 = 0.998, p < 0.001). In conclusion, we recommend the comparative CT method over the standard curve method because it is more economical in terms of both cost and labor. Although both aromatase activity and CYP19 mRNA were clearly detectable in testes of X. laevis, both aromatase enzyme activity and CYP19 gene expression were very low. Also, no significant relationships were found between aromatase enzyme activity and gene expression. This is likely due the fact that the aromatase enzyme may have been dormant at the developmental stage the frogs were in during the experiment.

Animals↗
PubMed1992

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↗
PubMed1992

Ultrastructural study of foetal and adult mouse renal tissue implanted in testis.

Kidneys of mice foetuses 15, 17, 19 days old, as well as kidneys of mice 1 and 4 weeks old of the pure C3H/SY species, were implanted into the right testis of 40 adult mice 1.5 to 2 months old, of the same species. The animals were sacrificed after 30 and 60 days and the evolution and development of the renal implants within the testis ware studied. The findings in the light as well as in the electron microscope, showed that the renal implants presented the histologic characters of nephroblastoma, which became clearer the more prolonged the time of the implantation was.

Animals↗
PubMed1990

Serum follicle stimulating hormone--predictor of cancer in the remaining testis in patients with unilateral testicular cancer.

In 10 of 13 patients with unilateral testicular cancer and subsequent invasive cancer or carcinoma in situ in the remaining testis, the follicle stimulating hormone (FSH) level was elevated after the first orchiectomy and before further treatment. In only 4 of 26 comparable control patients was the FSH level raised. This may be because elevated serum FSH often reflects disturbances in spermatogenesis and fertility, the latter being a known risk factor for testicular cancer. An elevated FSH level that occurs after orchiectomy for unilateral testicular cancer and before further treatment identifies patients at high risk of developing a tumour in the remaining testis.

Adolescent↗
PubMed2005

Expression of SRY proteins in both normal and sex-reversed XY fetal mouse gonads.

Sry, a single-copy gene on the Y-chromosome, acts dominantly to trigger differentiation of a testis from a gonadal primordium that otherwise develops into an ovary in mammals. Sry encodes a protein with a DNA-binding domain and probably acts as a transcription factor. However, the mode of SRY action in testis determination remains largely unknown. In the present study, we detected the endogenous SRY protein in normal XY fetal mouse gonads by Western blotting and immunohistochemistry. The tissue-specificity and ontogeny of the detected protein were consistent with those of Sry transcripts. Immunofluorescent double labeling revealed that the SRY protein was detected in the Sertoli cell lineage and was swiftly down-regulated concurrently with testis cord organization. Surprisingly, however, the SRY protein was detected in the entire gonad from the onset of its expression, not in parallel to the spatiotemporal pattern of testis cord organization. The SRY protein was also detected in the entire region of all B6.Y(TIR) fetal gonads, which were anticipated to undergo either partial or complete sex reversal. SRY down-regulation was considerably delayed, compared with control B6.XY gonads and was not associated with testis cord organization in B6.Y(TIR) gonads. We conclude that the testis-determining pathway is impaired at the site of SRY action in the B6.Y(TIR) gonad.

Animals↗
PubMed1998

Phenotypic manifestations during the development of the dominant and default gonads in mammals and birds.

The dominant embryonic gonad--testis in mammals and ovary in birds--secretes one or more morphogenetic substances that exert a major effect on the phenotype of the embryo. When deprived of their gonads, mammalian embryos develop into females, and avian embryos assume predominantly male characteristics, although retaining both oviducts. In order to fulfill their task of masculinizing the reproductive tract, mammalian testes grow and differentiate faster than ovaries. In birds the pattern is less straightforward. In 5-day-old embryos of White Leghorn chickens, sexual differentiation manifests itself in two different ways: (1) the gonads of ZZ embryos are larger, and on day 6 contain more protein and DNA than those of ZW embryos; (2) in both sexes, left gonads are larger than right gonads and contain a thick "germinal epithelium" capable of giving rise to an ovarian cortex under the influence of oestrogen. The pattern changes in embryos aged between 7 and 8 days, when the left gonad of ZW embryos outgrows all others, developing into an ovary, and when the bilateral asymmetry between left and right gonads increases in female embryos. A remnant of gonadal bilateral asymmetry is seen in the distribution of gonads in cases of true hermaphroditism in humans and other mammals. Whereas the initial fast growth of the mammalian testis is assumed to be due to one or more Y-chromosomal genes, that of the early avian testis is mostly simply explained as the effect in the disomic state of one or more genes on the Z chromosome. However, the later growth of the avian ovary is more likely to be due to oestrogen than to a direct gene effect. It is postulated that oestrogen has lost its power to determine ovarian development in mammals, in which both sexes are exposed to the oestrogen-rich environment of the uterus. Hence, the task of sex determination devolves on the fetal testis, whose early development and hormonal function are required to induce the male phenotype, the female phenotype arising in default mode.

Animals↗
PubMed2003

Insulin-like growth factor I (IGF-I) regulates endocrine activity of the embryonic testis in the mouse.

Insulin-like growth factor I (IGF-I) is important for gonadal and reproductive functions in mammals, although the physiological role of this growth factor during gonadal development in rodents remains largely unknown. Here, we examined the steady-state levels of IGF-I mRNA by the reverse transcriptase polymerase chain reaction (RT-PCR). IGF-I protein expression was also detected by Western blot. The effect of IGF-I as promoter of 17alpha-hydroxylase/C17-20 lyase and 17beta-hydroxysteroid dehydrogenase enzyme activity in vitro was evaluated by radioimmunoassay. Onset of IGF-I gene expression was on day E10 (urogenital ridge stage). IGF-I mRNA expression was markedly reduced on days E12 and E13 (testicular differentiation stage). IGF-I transcripts increased on day E14 and their transcription levels were maintained throughout the stages analyzed. Several IGF-I protein bands of 31-100 kDa were observed. Culture experiments demonstrated that 17alpha-hydroxyprogesterone and testosterone (T) secretion levels increased in the presence of IGF-I on days E11-E17. Additive effects of IGF-I plus (Bu)2cAMP were also seen during testicular development. It is proposed that IGF-I regulates the expression of key steroidogenic enzymes important for endocrine activity of the testis during prenatal development leading to establishment of the male phenotype and fertility.

17-Hydroxysteroid Dehydrogenases↗
PubMed1984

[Cystic testis dysplasia with ipsilateral kidney agenesis].

A 6-year-old boy was seen for a left side scrotal mass which developed within a few months. Orchidectomy revealed an enlarged testis with multiple cysts in the head of epididymis and cystic transformation of the rete. At the same time, ipsilateral renal agenesis was found. This is a very rare combined malformation of the urogenital system which is of unknown etiology. Its pathogenesis may be related to developmental defects at the proximal and distal portion of the wolffian duct.

Child↗
PubMed2006

Potency of testicular somatic environment to support spermatogenesis in XX/Sry transgenic male mice.

The sex-determining region of Chr Y (Sry) gene is sufficient to induce testis formation and the subsequent male development of internal and external genitalia in chromosomally female mice and humans. In XX sex-reversed males, such as XX/Sry-transgenic (XX/Sry) mice, however, testicular germ cells always disappear soon after birth because of germ cell-autonomous defects. Therefore, it remains unclear whether or not Sry alone is sufficient to induce a fully functional testicular soma capable of supporting complete spermatogenesis in the XX body. Here, we demonstrate that the testicular somatic environment of XX/Sry males is defective in supporting the later phases of spermatogenesis. Spermatogonial transplantation analyses using XX/Sry male mice revealed that donor XY spermatogonia are capable of proliferating, of entering meiosis and of differentiating to the round-spermatid stage. XY-donor-derived round spermatids, however, were frequently detached from the XX/Sry seminiferous epithelia and underwent cell death, resulting in severe deficiency of elongated spermatid stages. By contrast, immature XY seminiferous tubule segments transplanted under XX/Sry testis capsules clearly displayed proper differentiation into elongated spermatids in the transplanted XY-donor tubules. Microarray analysis of seminiferous tubules isolated from XX/Sry testes confirmed the missing expression of several Y-linked genes and the alterations in the expression profile of genes associated with spermiogenesis. Therefore, our findings indicate dysfunction of the somatic tubule components, probably Sertoli cells, of XX/Sry testes, highlighting the idea that Sry alone is insufficient to induce a fully functional Sertoli cell in XX mice.

Animals↗
PubMed1984

[Structural changes in the testis in complete removal of the pancreas and its resection].

The dog pancreas was resected completely or partially. The morphofunctional status of the testicle was examined at varying times after operation with the use of histological, histochemical and morphometric tests. The alterations discovered attest to the dependence of the structural shifts in the testicle on the type of surgery on the pancreas. Resection of the end parts caused temporary and insignificant changes in the testis. Resection of the central part with ligation and intersection of the main excretory ducts gave rise to dystrophic changes in the spermatogenic epithelium, disorders in the structural elements responsible for hormonal activity. Complete resection of the pancreas was early in affecting the morphofunctional status of the testicle. Ten to 15 days after operation profound dystrophic and atrophic changes were detectable in all the cells of the testicle. Injection of insulin postponed the animal's death, decelerated but not prevented the development of regressive changes in the testis.

Animals↗