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PubMed2002

INSL3/Leydig insulin-like peptide activates the LGR8 receptor important in testis descent.

Several orphan G protein-coupled receptors homologous to gonadotropin and thyrotropin receptors have recently been identified and named as LGR4-8. INSL3, also known as Leydig insulin-like peptide or relaxin-like factor, is a relaxin family member expressed in testis Leydig cells and ovarian theca and luteal cells. Male mice mutant for INSL3 exhibit cryptorchidism or defects in testis descent due to abnormal gubernaculum development whereas overexpression of INSL3 induces ovary descent in transgenic females. Because transgenic mice missing the LGR8 gene are also cryptorchid, INSL3 was tested as the ligand for LGR8. Here, we show that treatment with INSL3 stimulated cAMP production in cells expressing recombinant LGR8 but not LGR7. In addition, interactions between INSL3 and LGR8 were demonstrated following ligand receptor cross-linking. Northern blot analysis indicated that the LGR8 transcripts are expressed in gubernaculum whereas treatment of cultured gubernacular cells with INSL3 stimulated cAMP production and thymidine incorporation. The present study identified the ligand for an orphan G protein-coupled receptor based on common phenotypes of ligand and receptor null mice. Demonstration of INSL3 as the ligand for LGR8 facilitates understanding of the mechanism of testis descent and allows studies on the role of INSL3 in gonadal and other physiological processes.

Animals↗

PubMed1993

Bilateral germ cell tumors of the testis.

In a retrospective study of 530 patients with testicular germ cell tumors treated between 1977 and 1993, a group of 12 patients (2.26%) with bilateral testicular tumors was analyzed. While bilateral tumors were simultaneously present in two cases (both with different histologic types), consecutive development of a tumor in the contralateral testis was observed in 10 patients 5.25 years (range, 3-13.5 years) after orchiectomy for the first tumor. The authors highlight the variability of histologic types in both testes, the need for an individual therapeutic approach with a view to previous therapy for the first tumor, the need for hormonal replacement as well as the possibility of testicular prosthesis implantation following bilateral orchiectomy.

Adult↗

PubMed2005

Differential expression of p160 steroid receptor coactivators in the rat testis and epididymis.

OBJECTIVE: Androgens are critical for the development and maintenance of male sexual characteristics. Their action is mediated through the androgen receptor (AR). Ligand-bound AR interacts with coactivator proteins that mediate transcriptional activation. Such coactivators include three members of the 160 kDa proteins (p160s): SRC-1, TIF2/GRIP1, and p/CIP/RAC3/ACTR/AIB1/TRAM-1. The aim of this study was to investigate the expression of the three p160 coactivators and their association with AR in testis and epididymis. METHODS: We determined the localization of these three p160 coactivators in immature and mature rat testis, and epididymis by immunohistochemistry using the specific monoclonal antibodies. We also performed double immunofluorescence staining to examine whether p160s are colocalized with AR in these tissues. RESULTS: In seminiferous tubules of mature rat testis, SRC-1 and TRAM-1 immunoreactivity was found predominantly in spermatogonia and spermatocytes. In contrast, TIF2 was expressed predominantly in Sertoli cells. AR was coexpressed with TIF2 in this cell type. In immature rat testis, however, all three coactivators were expressed in both germ cells and Sertoli cells. In the epididymis, SRC-1 and TIF2 immunoreactivities were localized in nuclei of epithelial cells. However, TRAM-1 immunostaining was observed in the luminal portion of the cytoplasm with greater intensity than in the nucleus, especially in the caput epididymidis. CONCLUSIONS: The cell-type-specific expression of p160 coactivators suggests specific roles in male reproductive organs. Further, the strong cytoplasmic localization of TRAM-1 protein in epithelial cells of epididymis suggests that TRAM-1 may have additional role(s) in transcriptional regulation.

Aging↗

PubMed1981

Effects of LH-RH infusion, castration and cryptorchidism on gonadotrophin and testosterone secretion in developing rams.

The relationship between the pituitary gland and testis in rams was studied from birth to sexual maturity. The concentrations of LH, FSH and testosterone increased between 5 and 7 weeks of age; the rise was not correlated with any specific cytological change in the testis. An augmented pituitary response to LH-RH was demonstrated as levels of gonadotrophin increased. It is unclear whether this change in sensitivity plays a role in initiation of the pubertal process because Sertoli cell maturation, the earliest detectable change in the seminiferous epithelium, occurs between 17 and 21 weeks of age. Spermatocytes were first seen in biopsies taken at 31-36 weeks and spermatogenesis was established fully by 45 weeks. This second phase of testicular development was characterized by increases in prolactin, testosterone and LH. Leydig cells previously difficult to identify became recognizable at the time of sexual maturation. In newborn rams, castration produced significant increases in LH and FSH levels within 2-3 weeks, but higher basal FSH levels (2- to 3-fold) were observed at 5 than at 3 weeks of age. Cryptorchidism did not elevate LH or FSH significantly during the first year of life. FSH rose after this period to levels 2- to 3-fold higher than in normal rams, while LH and testosterone values remained in the normal range in spite of diminished spermatogenic activity; spermatids were absent and testis size was approximately 60% of that recorded in a normal ram. These studies demonstrate a rise in gonadotrophin and testosterone secretion in rams during the first 5-7 weeks of life, followed by a quiescent period of 8-9 months before a secondary increase occurs coincident with the establishment of sexual maturity.

Aging↗

PubMed1998

Evolution of the vertebrate epididymis.

This review examines the structure and function of the extratesticular sperm ducts of vertebrates in terms of their evolutionary development and adaptive significance. The primitive extratesticular duct system of Chondrichthyes is described as an example of the vertebrate archetype. Adaptations of the duct system in higher vertebrates have involved a loss of some structures and specialization of others. The duct system probably evolved as a homeostatic mechanism to facilitate fertilization and some embryological development under conditions protected from the external environment. However, it is argued that the ducts also play an important role in the competition between males to achieve paternity. In vertebrates that practise internal fertilization the ducts are involved in post-testicular maturation and storage of spermatozoa. The biological significance of post-testicular sperm maturation has not been resolved. By contrast, sperm storage is essential in most male vertebrates because of the slow rate of spermatogenesis, particularly in ectotherms. Sperm storage is also important in the competition between males for paternity as it enables a male to mate a 'partner' a number of times during an oestrus in order to reduce the prospect of being cuckolded by another male. The extent of sperm maturation and storage in the epididymis of particular vertebrates depends on the relative roles of the testis and its extragonadal ducts in the competition between males for paternity. These roles depend on a number of factors, including allometric limitations to testis size, metabolic rate and the development of endothermy, and the reproductive strategy of females of the species.

Animals↗

PubMed1991

[Adenocarcinoma of the rete testis. Review of the literature apropos of a new case].

The authors report the case of a 66 year old man with a Boden stage I adenocarcinoma of the rete testis treated by orchiectomy and adjuvant chemotherapy. Lung metastases developed 46 months later and were responsible for death despite further chemotherapy. Adenocarcinoma of the rete testis is an exceptional tumour, as only 23 cases satisfying the criteria defined by Feek and Hunter have been reported in the literature. The prognosis is poor even in the apparently localized forms (5 year survival less than 25%) and local recurrences and lung and/or hepatic metastases are frequent. Radiotherapy and chemotherapy appear to have little value.

Aged↗

PubMed2006

[Effects of nonylphenol on PCNA expression and aromatase expression in reproductive system of F1 generation].

OBJECTIVE: To elucidate the mechanism of the toxicity of nonylphenol (NP) to reproductive development by analyzing the PCNA and Aromatase expression of the F1 generation male reproductive system in perinatal period. METHODS: Nonylphenol was administrated to pregnant rats at doses of 50, 100 and 200 mg/kg, respectively, for 7 to 20 days of pregnancy. The rats were sacrificed at 20 days of pregnancy and 2 days after parturition. Their serum levels of estradiol and nonylphenol were determined. The histopathological examination and immune histochemical analysis on testis and epididymis were also performed. RESULTS: Significantly higher serum estradiol and nonylphenol levels were found in the pregnant rats treated with nonylphenol. Immune histochemical analysis showed that the PCNA expression levels of testis tissues of F1 generation rats, both 20-day-old fetus and 2-day-old neonatal rats, in 100 mg/kg and 200 mg/kg experiment groups were much lower than those in the control group. Both PCNA expression of epididymis and Aromatase expression of testis of the F1 generation rats after 2 days of birth in 200 mg/kg group were also lower than those in the control group. CONCLUSION: Nonylphenol can impair the development of testis and epididymis of the F1 generation in perinatal period.

Animals↗

PubMed1976

Influence of embryonic and adult testis on the differentiation of embryonic ovary in the mouse.

The development of 11 1/2-13 1/2-day embryonic mouse ovaries subjected to the influence of adult and embryonic testes was investigated. The environment of adult testis caused severe restriction of ovarian growth, but did not produce any effects which might be considered as masculinization. The presence of embryonic testis was distinctly unfavourable to the embryonic ovary, resulting in restriction of the growth of the latter and degeneration of oocytes. Reversal of the course of differentiation of genetically female germ cells has never been observed.

Animals↗

PubMed1994

An SRY-related sequence on the marsupial X chromosome: implications for the evolution of the mammalian testis-determining gene.

The SRY gene on the human, mouse, and marsupial Y chromosomes is the testis-determining gene that initiates male development in mammals. The SRY protein has a DNA-binding domain (high mobility group or HMG box) similar to those found in the high-mobility-group proteins. SRY is specific for the Y chromosome, but many autosomal genes have been identified that possess a similar HMG box region; those with the most closely SRY-related box regions form a gene family now referred to as SOX genes. We have identified a sequence on the marsupial X chromosome that shares homology with SRY. Sequence comparisons show near-identity with the mouse and human SOX3 gene (formerly called a3), the SOX gene which is the most closely related to SRY. We suggest here that the highly conserved X chromosome-linked SOX3 represents the ancestral SOX gene from which the sex-determining gene SRY was derived. In this model SOX3/SRY divergence and the acquisition of a testis-determining role by SRY might have preceded (and initiated) sex chromosome differentiation or, alternatively, might have been a consequence of X chromosome-Y chromosome differentiation initiated at the locus of an original sex-determining gene(s), later superseded by SRY.

Alleles↗

PubMed1978

[Structure of the follicular epithelium of the gonads Neva lamprey Lampetra fluviatilis (classification of the follicular epithelia of vertebrates)].

During its fluvial life, the ovarian follicular epithelium of Lampetra fluviatilis undergoes polarity formation--in the animal hemisphere the follicular epithelium is flattened, in the vegetative--it undergoes a secretory specialization: as the secrete is accumulating, the follicular cells increase in volume and height, acquiring a cubical form. In connection with monotonous or differentiating morpho-physiological alterations of follicular epithelium within a single follicle during the period of rapid oocytic growth, it is suggested to widen the idea on kinds of its secondary transformation in the vertebrates. It is suggested to differ: 1) common secondary transformation, when secondary flattening (for example, in birds) or secondary specialization (for example, in fish demersal roe) embraces the whole epithelium of the follicle. In case of common secretory specialization, it can be a) isomorphous--at identical convertion of the epithelium in the whole follicle (for example, in sheatfish), b) dimorphous--when there is a certain difference in the character and degree of secretory specialization of the follicular epithelium in various follicular areas (for example in Myxine glutinosa); 2) unipolar secondary transformation when the follicular epithelium undergoes secondary flattening or secretory specialization only in the area adjacent to one of the oocyte poles (for example, in Lametra fluviatilis and Blennis follis). Follicular epithelium of the lamprey testis, unlike in other Anamnia, does not form spermatocysts; implantation of spermatids and spermia into cytoplasm of the follicular cells is not observed. Thus, histological structure of Cyclostomata testis is at a lower stage of development than in other Anamnia.

Animals↗

PubMed1994

Transabdominal testicular descent is really ovarian ascent.

Some investigators have suggested that testicular descent relative to the ovary is actually caused by the relative upward growth of the structures adjacent to the testis and that in the early phase of descent the testis is anchored to the inguinal region as the embryo enlarges. This concept was founded on results from the dissection of human fetuses. In this study the development of the urogenital system in fetal mice is examined using scanning electron microscopy to determine the distance between the bladder neck and the lower pole of the gonad. The results of this study confirm that transabdominal descent of the testis relative to the ovary is in one sense really ascent of the ovary in the fetal mouse, while the testis is anchored to the inguinal region by the developed gubernaculum. The testis shows real movement at the beginning of the inguinoscrotal phase of testicular descent at birth.

Animals↗

PubMed1996

The testis isoform of the phosphorylase kinase catalytic subunit (PhK-gammaT) plays a critical role in regulation of glycogen mobilization in developing lung.

In order to identify the form of phosphorylase kinase catalytic subunit expressed in developing lung, degenerate polymerase chain reaction primers were designed based on conserved domains of the two known catalytic subunits, expressed primarily in muscle and testis. Amplification of cDNA from day 19 fetal rat lung followed by cloning and sequence analyses indicated that only the testis isoform of phosphorylase kinase (PhK-gammaT) was detectable in fetal lung. In situ hybridization analyses indicated that expression of PhK-gammaT RNA in developing lung tissue was widespread and not restricted to Type II epithelial cells; PhK-gammaT protein expression was temporally and spatially correlated with expression of PhK-gammaT RNA. PhK-gammaT RNA and protein expression was also characterized in the PhK-deficient glycogen storage disease (gsd) rat. PhK-gammaT RNA levels were similar in Type II cells isolated from wild type and gsd/gsd fetuses; in contrast, PhK-gammaT protein was virtually undetectable in gsd/ gsd Type II cells and enzyme activity was very low. These results suggest that PhK-gammaT plays a critical role in mobilization of glycogen during fetal lung development and that failure to catabolize glycogen in the gsd/gsd rat is related to an untranslatable PhK-gammaT RNA or unstable protein.

Amino Acid Sequence↗

PubMed1991

Immunogold electron microscopic localization of antigenic sites in the outer dense fiber region of rat sperm tail obtained by using antisera to two Sertoli cell secretory proteins.

Polyclonal antisera raised against polypeptide components of two rat Sertoli cell secretory proteins, designated protein S70 and S45-S35 heterodimeric protein on the basis of cell origin and estimated molecular weight, were used to identify antigenic sites in 1) rat testis, 2) cultured Sertoli cells, 3) developing spermatids (collected from spermatogenic stage-specific seminiferous tubular segments), and 4) epididymal sperm. Indirect immunofluorescence, immunoperoxidase, and immunogold electron microscopy (single and double labeling) were used. Immunocytochemical techniques have detected antigenic sites in 1) the cytoplasm of Sertoli cells in the intact seminiferous tubule and in culture in the form of a punctuate, granular-like pattern, and 2) the acrosome (but not the Golgi region) and tail of developing spermatids and sperm. In developing spermatids, the principal piece of the tail displays a characteristic apical-to-distal immunoreactive banding pattern that correlates both temporally and spatially with the reported multistep assembly of outer dense fibers along the axoneme. The immunoreactivity of the acrosome, connecting piece, and outer dense fibers of the sperm tail was confirmed by immunogold electron microscopy. A precise identification of the component(s) of the outer dense fiber region responsible for the antigenic homology with Sertoli cell secretory proteins is under investigation.

Animals↗

PubMed1999

[Cystic dysplasia of the rete testis and ipsilateral kidney agenesis in children].

BACKGROUND: Cystic dysplasia of rete testis, a rare abnormality, is often associated with renal agenesis. CASE REPORT: A 5-year-old boy was examined because he presented large scrotum. This was initially considered as hydrocele. Surgery showed a cystic dysplasia of the testis that in this patient was associated with ipsilateral renal agenesis. CONCLUSION: This congenital abnormality, explained on the basis of embryological development, has been reported in 15 children. The testis appears cystic at surgical exploration; echography can affirm diagnosis and MRI can give specific features. A conservative attitude is proposed as this lesion is benign. Long-term follow-up is recommended for possible painful effects or growth of the lesion.

Child, Preschool↗

PubMed1994

Possible physiological bases for contraceptive techniques in the male.

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

Blood-Testis Barrier↗

PubMed2001

Germ cells, gonads and sex reversal in marsupials.

The formation of the testis or ovary is a critical step in development. Alterations in gonadal development during fetal or postnatal life can lead to intersexuality or infertility. Several model systems have been particularly useful in studying gonadal differentiation, the eutherian mammal and amphibia, fish, and birds. However, marsupials provide a unique opportunity to investigate gonadal development and the interactions of genes and hormones in gonadal differentiation and germ cell development in all mammals. On the one hand the genetic mechanisms appear to be identical to those in eutherian mammals, including the testis-determining SRY gene. On the other hand, marsupials retain in part the plasticity of the amphibian gonad to hormonal manipulation. It is possible to induce female to male and also male to female gonadal sex reversal in marsupials by hormonal manipulation, and oestradiol can induce male germ cells to enter meiosis at the time the oogonia do. In addition, in marsupials the development of the scrotum and mammary glands are independent of testicular androgens and instead are controlled by a gene or genes on the X-chromosome. Thus marsupials provide a number of opportunities for manipulating the sexual differentiation of the gonads that are not possible in eutherian mammals and so provide a unique perspective for understanding the common mechanisms controlling sexual development.

Animals↗

PubMed2006

Comparative genome analysis of the neurexin gene family in Danio rerio: insights into their functions and evolution.

Neurexins constitute a family of proteins originally identified as synaptic transmembrane receptors for a spider venom toxin. In mammals, the 3 known Neurexin genes present 2 alternative promoters that drive the synthesis of a long (alpha) and a short (beta) form and contain different sites of alternative splicing (AS) that can give rise to thousands of different transcripts. To date, very little is known about the significance of this variability, except for the modulation of binding to some of the Neurexin ligands. Although orthologs of Neurexins have been isolated in invertebrates, these genes have been studied mostly in mammals. With the aim of investigating their functions in lower vertebrates, we chose Danio rerio as a model because of its increasing importance in comparative biology. We have isolated 6 zebrafish homologous genes, which are highly conserved at the structural level and display a similar regulation of AS, despite about 450 Myr separating the human and zebrafish species. Our data indicate a strong selective pressure at the exonic level and on the intronic borders, in particular on the regulative intronic sequences that flank the exons subject to AS. Such a selective pressure could help conserve the regulation and consequently the function of these genes along the vertebrates evolutive tree. AS analysis during development shows that all genes are expressed and finely regulated since the earliest stages of development, but mark an increase after the 24-h stage that corresponds to the beginning of synaptogenesis. Moreover, we found that specific isoforms of a zebrafish Neurexin gene (nrxn1a) are expressed in the adult testis and in the earliest stages of development, before the beginning of zygotic transcription, indicating a potential delivery of paternal RNA to the embryo. Our analysis suggests the existence of possible new functions for Neurexins, serving as the basis for novel approaches to the functional studies of this complex neuronal protein family and more in general to the understanding of the AS mechanism in low vertebrates.

Alternative Splicing↗

PubMed1986

[Development of the urogenital tract in double-bodied pleurodele chimeras. Effect of position on interactions between the genital glands of different sex].

Chimeric grafts of the embryos of the urodele amphibian (Pleurodeles waltlii Michah.) produced viable, double-bodied animals having two pairs of genital glands of the same sex [homosexual chimeras: anterior testes--posterior testes (male----male) and anterior ovaries--posterior ovaries (female----female)] or of different sex [(heterosexual chimeras: anterior ovaries--posterior testes (female----male) and anterior testes--posterior ovaries (male----female)]. 115 chimeras aged 5 months to 15 years were analysed. Gonadal development in a same animal was observed at different times by exploratory laparotomy. The testes of heterosexual chimeras were removed in order to prevent their inhibitory effect on the ovaries (freemartin effect). The 115 experimental animals were classified according to gonadal development as follows: 47 male----male chimeras (41%), 26 female----female chimeras (23%), 13 female----male chimeras (11%), 29 male----female chimeras (25%). As a rule, male----male chimeras only developed three normal testes. The fourth testis, always situated in the anterior part of the chimera, remained vestigial; nevertheless, it could attain a normal size if the other three testes were removed. female----female chimeras usually had four ovaries; the times of vitellogenesis and of sexual maturity were synchronous in all four ovaries. The anterior ovaries of female----male chimeras were always inhibited and the posterior testes were always normal. male----female chimeras always had normal anterior testes but their posterior ovaries were often weakly inhibited. The high number of male----male chimeras and the low number of female----female ones could be due to a phenotypic reversal of the anterior ovaries in some of the female----male chimeras. The number of male----female chimeras (corresponding to the theoretical number) suggests that the phenotypic sex of the posterior ovaries was not reversed. The freemartin effect in double-bodied heterosexual chimeras depended on the location of the ovaries in relation to the testes. The effect was more significant on the anterior ovaries when posterior testes were present. No or weak freemartin effect was observed when the posterior ovaries developed facing the anterior testes; in about 60% of cases, a reciprocal inhibition or an equilibrium between gonads of different sex occurred.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗