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At least 343 records · Page 19Linked to original sources

PubMed2006

Sexually dimorphic regulation of inhibin beta B in establishing gonadal vasculature in mice.

Sexually dimorphic differentiation of gonads is accomplished through balanced interactions between positive and negative regulators. One of the earliest features of gonadal differentiation is the divergent patterning of the vasculature. A male-specific coelomic vessel develops on the anterior to posterior of the XY gonad, whereas this vessel is absent in XX gonads. It is postulated that the testis-determining gene Sry controls formation of the coelomic vessel, but the exact molecular mechanism remains unknown. Here we reveal a novel role for inhibin beta B in establishing sex-specific gonad vasculature. In the testis, inhibin beta B contributes to proper formation of the coelomic vessel, a male-specific artery critical for testis development and, later in development, hormone transportation. On the other hand, in the ovary, inhibin beta B is repressed by WNT4 and its downstream target follistatin, leading to the absence of the coelomic vessel. When either Wnt4 or follistatin was inactivated, the coelomic vessel appeared ectopically in the XX ovary. However, when inhibin beta B was also removed in either the Wnt4-null or follistatin-null background, normal ovarian development was restored and no coelomic vessel was found. Our results indicate that the sex-specific formation of the coelomic vessel is established by positive components in the testis as well as an antagonizing pathway from the ovary. Inhibin beta B is strategically positioned at the intersection of these opposing pathways.

Animals↗

PubMed1998

A novel nuclear receptor heterodimerization pathway mediated by orphan receptors TR2 and TR4.

A unique heterodimerization pathway involving orphan receptors TR2 and TR4 is demonstrated. TR2 and TR4 preferentially form heterodimers in solution as well as on DNA elements containing a direct repeat-5 (DR5). The in vitro interaction between TR2 and TR4 is demonstrated by the yeast and the mammalian two-hybrid interaction assays, the pull-down assay, and the gel mobility shift assay. The in vivo interaction is demonstrated by following the intracellular localization of fusion receptors tagged with a green fluorescent protein. The dimerization is mediated by the ligand binding domains, and the three leucine residues on helix 10 of TR2 are critical for this interaction. In addition, coexpression of these two receptors exerts a much stronger repressive activity on a DR5-containing reporter than expressing either receptor alone. In the developing testis, TR2 and TR4 are coexpressed in the same testicular cell populations and exhibit a parallel pattern of expression along development. The preferential heterodimerization between TR2 and TR4 and their coexistence in specific germ cell populations suggest a physiological role of TR2/TR4 heterodimers in germ cell development.

Amino Acid Sequence↗

PubMed1988

Müllerian inhibiting substance production and testicular migration and descent in the pouch young of a marsupial.

The ontogeny of Müllerian inhibiting substance (MIS) production by the developing testis of an Australian marsupial, the tammar wallaby (Macropus eugenii), was determined during pouch life using an organ-culture bioassay of mouse fetal urogenital ridge. This information was related to the morphological events during testicular migration and descent. MIS biological activity was found in testes (but not ovaries or liver) of pouch young from 2 to 85 days of age. MIS production had commenced by day 2, which is within a day of the first gross morphological signs of testicular differentiation. Müllerian duct regression occurred between 10 and 30 days, which partly coincided with testicular migration to the inguinal region and enlargement of the gubernacular bulb (15 to 30 days). These observations are consistent with the hypothesis that MIS may be involved in testicular transabdominal migration. The epididymis commenced development and growth only after the testis had descended through the inguinal ring. This provides no support for the suggestion that the epididymis is involved in testicular descent into the scrotum. The basic sequence of events in post-testicular sexual differentiation in the wallaby is sufficiently similar to that seen in eutherian mammals to make it an excellent experimental model for future studies of testicular differentiation, migration and descent.

Animals↗

PubMed1995

Combined Leydig cell and Sertoli cell dysfunction in 46,XX males lacking the sex determining region Y gene.

We have evaluated 3 individuals with a rare form of 46,XX sex reversal. All of them had ambiguous external genitalia and mixed wolffian and müllerian structures, indicating both Leydig cell and Sertoli cell dysfunction, similar to that of patients with true hermaphroditism. However, gonadal tissue was not ovotesticular but testicular with varying degrees of dysgenesis. SRY sequences were absent in genomic DNA from peripheral leukocytes in all 3 subjects. Y centromere sequences were also absent, indicating that testis development did not occur because of a low level mosaicism of Y bearing cells. The subjects in this report demonstrate that there is a continuum in the extent of testis determination in SRY-negative 46,XX sex reversal, ranging from nearly normal to minimal testicular development.

Child↗

PubMed1989

Normal testis determination in the mouse depends on genetic interaction of a locus on chromosome 17 and the Y chromosome.

We previously described a locus on chromosome (Chr) 17 of the mouse that is critical for normal testis development. This locus was designated "T-associated sex reversal" (Tas) because it segregated with the dominant brachyury allele hairpin tail (Thp) and caused gonads of C57BL/6J XY, Thp/+ individuals to develop as ovaries or ovotestes rather than as testes. To clarify the inheritance of Tas, we investigated the effects of T-Orleans (TOrl), another brachyury mutation, on gonad development. We found that gonads of C57BL/6J XY, Thp/+ and TOrl/+ mice develop ovarian tissue if the Y chromosome is derived from the AKR/J inbred strain, whereas normal testicular development occurs in the presence of a Y chromosome derived from the C57BL/6J inbred strain. From these observations we conclude that: (1) Tas is located in a region on Chr 17 common to the deletions associated with Thp, and TOrl, and (2) the Y-linked testis determining gene, Tdy, carried by the AKR/J inbred strain differs from that of the C57BL/6J inbred strain. We suggest that in mammals Tdy is not the sole testis determinant because autosomal loci must be genetically compatible with Tdy for normal testicular development.

Animals↗

PubMed2005

Molecular cloning of a new member of TEKTIN family, Tektin4, located to the flagella of rat spermatozoa.

Tektins are composed of a family of filament-forming proteins associated with ciliary and flagellar microtubules. A new member of the TEKTIN gene family, which was designated as rat Tektin4, was obtained by PCR technique combined with yeast two-hybrid screening. Rat Tektin4 cDNA consists of 1,341 bp encoding a 52 kDa protein of 447 amino acids. Tektin4 protein contains a Tektin domain including a nonapeptide signature sequence (RPNVELCRD), which is a prominent feature of Tektins. Its amino acid sequence showed 29% approximately 58% identities to that of other Tektin family proteins registered in the public databases. Tektin4 gene, which was mapped to rat chromosome 10q12, is composed of six exons and spanning 5 kb. Reverse-transcriptional-PCR (RT-PCR) analysis indicated that Tektin4 was predominantly expressed in testis and its expression was upregulated during testis development. In situ hybridization analysis showed that Tektin4 mRNA was localized in round spermatids in the seminiferous tubules of the rat testis. Tektin4 protein was predominantly localized in the flagella of spermatozoa, suggesting that it might works as a flagellar component requisite for flagellar stability or sperm motility.

Amino Acid Sequence↗

PubMedDate not supplied

Cyclophosphamide modulates gene expression in neonatal rat testis following antenatal exposure to fetuses during testicular differentiation.

The present study was designed to evaluate the altered gene expression in neonatal rat testis after antenatal exposure of cyclophosphamide (one time single dose of either 2, 10, or 20 mg/kg body weight) to the developing fetuses, especially at the time of male sex differentiation. The rationale behind these experiments is to know about the involvement of Y-chromosome gene-dependent product(s) associated with gonadal dysfunction. Using SDS-polyacrylamide gel electrophoresis and photosensitive silver staining technique, the study shows that the variety of proteins of different molecular weight ranges 40,000 to 127,000 Da are modulated by cyclophosphamide exposure to the developing testis. Interestingly, the overexpression of one protein of 74,500 Da was observed both in supernatant as well as in pallet fractions. The qualitative and quantitative regulation of newly synthesized protein appearance or disappearance is observed in a dose-dependent manner.

Animals↗

PubMed1976

[Tubular structure and germ cell distribution of cryptorchid or normal testes in early childhood (author's transl)].

INTRODUCTION: Many recent publications have demonstrated that the cryptorchid testicle (and, to a lesser extent, the descended partner) are progressively injured from the second year of life onwards. Do these injuries occur in an organ which has been healthy up to this time or are they superimposed on a structurally abnormal testicle? In order to answer this, parts of cryptorchid testicles, of the descended partners, and of normal testicles were compared by histological examination of serial sections. MATERIAL AND METHODS: Parts of four testes from children aged 4-7 months (2 specimens obtained by biopsy and 2 from autoptic material) and parts of four testes from children 1 1/2 years old (2 obtained by biopsy and 2 from autoptic material) were examined. The biopsies were fixed in Stieve's fixative. Tissue samples from clinically healthy children who had died suddenly were fixed in 4% formalin. The tissue was embedded in paraffin and sectioned serially; 6 mum sections were stained with HE. The spermatogonia in each cross-section and in each oblique section of a same tubule were counted and the counts of the latter were adjusted to a cross-section 50-60 mum in diameter. This counting technique did not alter the density of spermatogonia. The graphs present data on the density of spermatogonia through the lengths of the tubules examined and demonstrate tubular branching and blind ends. In the first year of life the cryptorchid testis and its descended partner showed repeated long sections lacking spermatogonia in the same tubule, whereas in normal testes the spermatogonia were more evenly distributed. The cryptorchid testis showed increased tubule branching in the areas examined. In the second year of life the tubules of the cryptorchid testis and its descended partner manifest areas free of germ cells, increased branching, and blind ends. The cryptorchid testis also had a tubule completely free of spermatogonia. The germ cell-free parts were always associated with a smaller tubule diameter than normal. The normal testes did not disclose increased branching or spermatogonium-free areas within similar lengths of tubules and showed an even distribution of spermatogonia. DISCUSSION: The different distribution of spermatogonia within the tubules and the increased branching of the tubules in cryptorchid testes indicate a previous disturbance of testis development.

Age Factors↗

PubMed2005

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

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

Animals↗

PubMed2007

Sex-specific windows for high mRNA expression of DNA methyltransferases 1 and 3A and methyl-CpG-binding domain proteins 2 and 4 in human fetal gonads.

DNA methyltransferases (DNMTs) and 5-methyl-CpG-binding domain proteins (MBDs) are involved in the acquisition of parent-specific epigenetic modifications in human male and female germ cells. Reverse Northern blot analyses demonstrated sex-specific differences in mRNA expression for the maintenance DNMT1 and the de novo DNMT3A in developing testis and ovary. In fetal testis DNMT1 and DNMT3A expression peaked in mitotically arrested spermatogonia around 21 weeks gestation. In fetal ovary transcriptional upregulation of DNMT1 and DNMT3A occurred during a very brief period at 16 weeks gestation, when the oocytes proceeded through meiotic prophase. Fetal gonads showed several fold higher DNMT3A expression levels than fetal brain and adult tissues. The most abundant DNMT3A isoform in fetal testis and ovary was DNMT3A2, whereas in all other analyzed tissues DNMT3A1 predominated. The catalytically inactive DNMT3A3 isoform was also present at relatively high levels in developing gonads and may perform a regulatory function(s). In both male and female fetal gonads expression of genes for MBD2 and MBD4, which may be implicated in chromatin remodeling of methylated genomic DNA sequences, was tightly linked to DNMT expression. We propose that the sex-specific time windows for concomitant upregulation of DNMT1, DNMT3A, MBD2, and MBD4 are associated with prenatal remethylation of the human male and female germ line.

DNA (Cytosine-5-)-Methyltransferase 1↗

PubMed1992

Steroid hormone content of the gonads of the tammar wallaby during sexual differentiation.

The gonads of the tammar wallaby, Macropus eugenii, are sexually indifferent at birth (Day 0) despite the fact that phenotypic sexual differentiation has already commenced as evidenced by the presence of a scrotum in males and mammary anlagen in females. The seminiferous cords of the testis first become clearly recognizable on Day 2 of pouch life, and ovarian differentiation is recognizable by Day 10. To monitor the endocrine development of the gonads during sexual differentiation of the urogenital tract, we measured the steroid hormone content in 92 pools of gonads from male and female tammar pouch young from the day of birth to 206 days of pouch life. Progesterone, estradiol, and dihydrotestosterone concentrations were low (less than 0.05 ng/mg protein) in both ovaries and testes at all stages examined, and testosterone concentrations were uniformly low in ovaries. Testosterone concentrations in testes were low on Days 0-4, averaging about 0.2 ng/mg protein; they rose by Days 5-10 to an average of 0.9 ng/mg protein, remained elevated until about Day 40, and thereafter fell to values similar to those in the ovaries. The phallus and urogenital sinus were able to convert testosterone to dihydrotestosterone from the earliest stages examined (Days 10 and 11). Thus in the tammar wallaby, as in eutherian mammals, testosterone is the androgen secreted by the developing testis, and dihydrotestosterone is formed in certain androgen target tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

PubMed1993

Blastocysts prepare for the race to be male.

Recent findings in different mammalian species have demonstrated that XY embryos grow faster than XX embryos before the gonads are differentiated. In mice and cattle, accelerated development is already evident in XY blastocysts, while in the rat and in human fetuses a quantitative sex difference has been shown to be present before testicular differentiation has occurred. These data demonstrate that in these species the histological differentiation of the testis, which occurs early and rapidly, is preceded by an increased growth rate of the embryo. This may be expected to increase the probability of the gonad reaching the threshold for testis development, since it is known that developmental delay can result in ovarian differentiation. It is postulated that the fast development of the male may be an adaptation to the reproductive biology of eutherian mammals, in which development of both sexes occurs in the hormonal environment of the uterus. The question is raised as to a possible connection between sex-related growth and other sex differences, such as longevity.

Blastocyst↗

PubMed2005

Identification of a novel substrate for tyrosine kinase in human testes.

Identification of genes specifically expressed in adult and fetal testes is important in furthering our understanding of testis development and function. In this study, a novel human specific transcript, designated NYD-SP10, was identified by hybridization of adult and fetal human testis probes with a human cDNA microarray. NYD-SP10 (GenBank Accession no. AF332192) was expressed at a higher level in adult testes than in fetal testes. Bioinformatic analysis illustrated NYD-SP10 is a splice variant of regulatory factor X4, while it is lack of RFX DNA-binding domain which binds to the X box of MHC class II genes. Most telling of all, NYD-SP10 uniquely possesses a tyrosine kinase phosphorylation site. Expression profiles demonstrated NYD-SP10 is specifically and strongly expressed in human adult testes and ejaculated spermatozoa. Taken together, these results suggest that NYD-SP10 is a novel testis-specific gene and it is possibly a novel substrate for tyrosine kinase and involved in the function of human spermatozoa, especially during capacitation.

Adult↗

PubMed1992

Occurrence of Pomphorhynchus laevis Müller 1776 (Acanthocephala) in Silurus glanis (L.) from the River Po.

The sheatfish, Silurus glanis (L.), from the terminal part of River Po was examined for the presence of helminth parasites. Of 182 S. glanis specimens, 95 (52.2%) were infected with the acanthocephalan Pomphorhynchus laevis. Mid-gut followed by fore-gut appeared to be the most infected portions of host alimentary canal. In 45 sheatfish of total length < or = 40 cm, specimens of P. laevis were found encapsulated in mesenteric and peritoneal tissues. A comparison between light and electron microscopy on features and stages of testis development in both encapsulated male P. laevis and intestinal male parasites showed that the encysted acanthocephalans were immature; mature spermatozoa were rarely found within the testis of worms from the alimentary canal. Among extraintestinal P. laevis specimens, the presumable eversion of parasite praesoma was observed and described. The results of the present survey suggest that small-size individuals of S. glanis could be used as paratenic host by P. laevis during its life cycle in the study area.

Acanthocephala↗

PubMed2003

Endothelial and steroidogenic cell migration are regulated by WNT4 in the developing mammalian gonad.

The signalling molecule WNT4 has been associated with sex reversal phenotypes in mammals. Here we show that the role of WNT4 in gonad development is to pattern the sex-specific vasculature and to regulate steroidogenic cell recruitment. Vascular formation and steroid production in the mammalian gonad occur in a sex-specific manner. During testis development, endothelial cells migrate from the mesonephros into the gonad to form a coelomic blood vessel. Leydig cells differentiate and produce steroid hormones a day later. Neither of these events occurs in the XX gonad. We show that WNT4 represses mesonephric endothelial and steroidogenic cell migration in the XX gonad, preventing the formation of a male-specific coelomic blood vessel and the production of steroids. In the XY gonad, Wnt4 expression is downregulated after sex determination. Transgenic misexpression of Wnt4 in the embryonic testis did not inhibit coelomic vessel formation but vascular pattern was affected. Leydig cell differentiation was not affected in these transgenic animals and our data implies that Wnt4 does not regulate steroidogenic cell differentiation but represses the migration of steroidogenic adrenal precursors into the gonad. These studies provide a model for understanding how the same signalling molecule can act on two different cell types to coordinate sex development.

Animals↗

PubMed2005

Zinc-regulating proteins, ZnT-1, and metallothionein I/II are present in different cell populations in the mouse testis.

Zinc ions play an important role in testis development and spermatogenesis. Thus, nutritional zinc deficiency leads to aberrant testicular development, reduced spermatogenesis, and male sterility. The precise actions of zinc in mediating these functions and the mechanisms by which zinc is itself regulated in the testis, however, have not been adequately elucidated. We have assessed the distribution of the zinc-regulating proteins ZnT-1 and metallothionein I/II (MT I/II) in the mouse seminiferous tubule. Co-labeling for ZnT-1 and MT I/II demonstrated unique patterns of distribution for these proteins, with ZnT-1 present in Sertoli cells in addition to luminal spermatozoa and MT I/II restricted to spermatocytes. These findings were confirmed by dual-label immunofluorescence for ZnT-1 and the Sertoli cell marker, vimentin, and by immunoelectron microscopy. The differential expression patterns of ZnT-1 and MTs support the hypothesis that ZnT-1 and MTs play different roles in the regulation of intracellular zinc in this organ. The specific expression of ZnT-1 in the Sertoli cells, moreover, is consistent with their role in maintaining a nurturing, closely regulated environment for spermatogenesis.

Animals↗

PubMed2006

Sry and the hesitant beginnings of male development.

In mammals, Sry (sex-determining region Y gene) is the master regulator of male sex determination. The discovery of Sry in 1990 was expected to provide the key to unravelling the network of gene regulation underlying testis development. Intriguingly, no target gene of SRY protein has yet been discovered, and the mechanisms by which it mediates its developmental functions are still elusive. What is clear is that instead of the robust gene one might expect as the pillar of male sexual development, Sry function hangs by a thin thread, a situation that has profound biological, medical and evolutionary implications.

Amino Acid Sequence↗

PubMed1992

Maturation and regulation of the motility of spermatozoa in the epididymis of the tammar wallaby (Macropus eugenii).

Demembranated spermatozoa from the rete testis developed vigorous flagellation when reactivated with ATP, but showed no forward progression such as that seen in samples from the cauda epididymidis. The proportion of spermatozoa that were reactivated was smaller for samples from the rete testis than from the cauda epididymidis. Studies in vitro of undiluted micropuncture samples from the epididymis indicated that the activity of spermatozoa is suppressed as they develop the capacity for motility. However, as spermatozoa spontaneously became activated during the collection or subsequent incubation of undiluted samples, it was concluded that the suppressive action is labile. The activity of spermatozoa in vitro was examined in diluted samples from the cauda epididymidis. A concentration of 2.5 mmol extracellular calcium/l was better than lower concentrations. Diluents at pH 5.5 completely inhibited sperm motility when they contained 20 mmol lactate/l (but not glutamate) and the effect was reversed by readjusting the diluent to pH 7.4. However, lactate was not considered to suppress sperm motility in situ, as the plasma from the cauda epididymidis contained only 2.7 +/- 0.5 mmol lactate/l. There was no effect of sodium concentration (1 and 115 mmol/l), pH (5.5 and 7.4) or amiloride (0 and 1 mmol/l) on sperm motility, indicating that motility is not dependent on the concentration of sodium above 1 mmol/l or on a sodium-proton exchange system. The relative viscosity of plasma from the cauda epididymidis did not affect the motility of spermatozoa.

Animals↗