SEARCH · PubMed Health

Results for “testis development”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 433 records · Page 24Linked to original sources

PubMed1997

Metachronous development of malignant Leydig cell tumor.

Leydig cell tumor (LCT), a rare testicular tumor, is malignant in only about 10% of the cases. We report the case of a patient with bilateral malignant LCTs that developed metachronously. After undergoing a right inguinal orchiectomy for a malignant LCT at the age of 43 years, the patient was given cisplatin-based chemotherapy for suspected para-aortic lymph node metastasis. Eighteen months after the right orchiectomy, examination of a left testicular biopsy specimen showed a malignant LCT and a left inguinal orchiectomy was performed. Histologically, the initial malignant LCT exhibited a highly pleomorphic appearance with mitotic figures (58/10 HPF), whereas the second malignant LCT showed fewer mitoses (2/10 HPF). The proliferating cell nuclear antigen (PCNA)-labelling index in these tumors also differed (right-sided tumor, 50%; left-sided tumor, 28%). These findings suggest that the malignant LCT in the left testis developed as a second primary rather than as a metastatic tumor. There have been no known similar cases, although three cases of malignant LCT with contralateral metastasis have been reported.

Adult↗

PubMed2001

Age-dependent activin receptor expression pinpoints activin A as a physiological regulator of rat Sertoli cell proliferation.

It is currently believed that the fertility level of the adult mammalian testis is related to the total number of Sertoli cells, which is established in the early prepubertal life. We have previously reported that, in an in-vitro system, terminal Sertoli cell proliferation is sustained by activin A in concert with FSH. In this paper, we have addressed the question of whether this activin A effect correlates with activin receptor II (ActRII) expression pattern during early post-natal testis development. We first determined the precise developmental interval of activin proliferative effect on Sertoli cells in vitro and then analysed the expression of ActRII in purified testicular cell populations by Northern blot and in-situ hybridization. While the 3 kb ActRII isoform was widely expressed at different ages and in several testicular cells, including Sertoli cells, germ cells and myoid cells, the canonical 6 kb ActRII isoform was specifically and transiently expressed at a high rate in Sertoli cells at 7-9 days after birth, the time when these cells respond to activin A in vitro. In the light of these results, we conclude that activin A regulates terminal Sertoli cell proliferation in the rat testis and that this effect is mediated by the 6 kb isoform of ActRII.

Activin Receptors, Type II↗

PubMed2004

Gonadal dysgenesis without adrenal insufficiency in a 46, XY patient heterozygous for the nonsense C16X mutation: a case of SF1 haploinsufficiency.

Targeted disruption of the orphan nuclear receptor SF1 results in the absence of adrenals and gonads, establishing that this transcription factor is implicated in gonadal determination and adrenal development. Four human SF1 gene mutations have been described to date: three (G35E, R92Q, R255L) were responsible for adrenal insufficiency associated with a gonadal dysgenesis in two 46, XY individuals, one (8 bp deletion in exon 6) resulted in gonadal dysgenesis without adrenal insufficiency. We identified a new heterozygous SF1 gene mutation, C16X, in a 46, XY patient showing gonadal dysgenesis with normal adrenal function: low basal levels of AMH and testosterone (T), weak T response to hCG, hypoplastic testes with abundant seminiferous tubules but rare germ cells. This mutation causes premature termination of translation and should abolish all SF1 activity. Therefore haploinsufficiency could explain the deleterious effect of this mutation in our patient suggesting that testis development is more SF1 dose-dependent than adrenal development. Although the same mechanism explains the deleterious effects of SF1 missense mutations, recent studies have demonstrated an additional dominant negative effect. These data suggest that heterozygous mutation impaired adrenal development only if the two mechanisms, gene dosage and dominant negative effects occur.

Adrenal Glands↗

PubMed2002

A model system for study of sex chromosome effects on sexually dimorphic neural and behavioral traits.

We tested the hypothesis that genes encoded on the sex chromosomes play a direct role in sexual differentiation of brain and behavior. We used mice in which the testis-determining gene (Sry) was moved from the Y chromosome to an autosome (by deletion of Sry from the Y and subsequent insertion of an Sry transgene onto an autosome), so that the determination of testis development occurred independently of the complement of X or Y chromosomes. We compared XX and XY mice with ovaries (females) and XX and XY mice with testes (males). These comparisons allowed us to assess the effect of sex chromosome complement (XX vs XY) independent of gonadal status (testes vs ovaries) on sexually dimorphic neural and behavioral phenotypes. The phenotypes included measures of male copulatory behavior, social exploration behavior, and sexually dimorphic neuroanatomical structures in the septum, hypothalamus, and lumbar spinal cord. Most of the sexually dimorphic phenotypes correlated with the presence of ovaries or testes and therefore reflect the hormonal output of the gonads. We found, however, that both male and female mice with XY sex chromosomes were more masculine than XX mice in the density of vasopressin-immunoreactive fibers in the lateral septum. Moreover, two male groups differing only in the form of their Sry gene showed differences in behavior. The results show that sex chromosome genes contribute directly to the development of a sex difference in the brain.

Animals↗

PubMed2001

Reproductive function in protein kinase inhibitor-deficient mice.

The protein kinase inhibitor (PKI) family includes three genes encoding small, heat-stable inhibitors of the cyclic AMP-dependent kinase PKA. Each PKI isoform contains a PKA inhibitory domain and a nuclear export domain, enabling PKI to both inhibit PKA and remove it from the nucleus. The PKIbeta isoform, also known as testis PKI, is highly expressed in germ cells of the testis and is found at more modest levels in other tissues. In order to investigate its physiological role, we have generated PKIbeta knockout mice by gene targeting. These mice exhibit a partial loss of PKI activity in testis but remain fertile with normal testis development and function. PKIbeta knockout females also reproduce normally. The PKIbeta mutants were crossed with our previously derived PKIalpha mutants to obtain double-knockout mice. Remarkably, these mice are also viable and fertile with no obvious physiological defects in either males or females.

Animals↗

PubMed1994

FMRFamide-related peptides in Hymenolepis diminuta: immunohistochemistry and radioimmunoassay.

The localization of FMRFamide-related peptide (FaRP) immunoreactivity was determined during different stages of development of the rat tapeworm Hymenolepis diminuta. In the adult worm (14 days old), FaRP immunostaining was most intense in the scolex and concentrated in the central nervous system (cerebral ganglia and transverse commissures) and around the lips of the suckers. In the strobila, medial and lateral longitudinal nerve cords (LNCs) and ladder-like connecting commissures were the only tissue stained. Immunoreactivity in the medial LNCs of the adult tapeworms extended only to and included proglottides containing developing testis and seminal receptacle but disappeared in proglottides in which primordial ovaries were first detected. Radioimmunoassay confirmed that FaRPs were concentrated in the scolex/neck region of the adult worm (3.9 +/- 1.5 pmol mg protein-1), whereas the lowest concentrations (0.2 +/- 0.19 pmol mg protein-1) were recovered from the regions of the strobila containing shelled eggs. The pattern of FaRP immunoreactivity observed in 5- and 7-day-old worms was similar to that seen in adult worms, but in 2- and 3-day-old worms the pattern of immunoreactivity observed in the cerebral ganglia, transverse commissures, and LNCs differed significantly as compared with that seen in older worms. These results indicate differential utilization and/or roles for FaRPs during development and suggest both central and sensory roles in this tapeworm.

Amino Acid Sequence↗

PubMed2000

Regulation of germ cell and Sertoli cell development by activin, follistatin, and FSH.

We have demonstrated a role for activin A, follistatin, and FSH in male germ cell differentiation at the time when spermatogonial stem cells and committed spermatogonia first appear in the developing testis. Testis fragments from 3-day-old rats were cultured for 1 or 3 days with various combinations of these factors, incubated with bromodeoxyuridine (BrdU) to label proliferating cells, and then processed for stereological analysis and detection of BrdU incorporation. Gonocyte numbers were significantly elevated in cultures treated with activin, while the combination of FSH and the activin antagonist, follistatin, increased the proportion of spermatogonia in the germ cell population after 3 days. All fragment groups treated with FSH contained a significantly higher proportion of proliferating Sertoli cells, while activin and follistatin each reduced Sertoli cell division. In situ hybridization and immunohistochemistry on normal rat testes demonstrated that gonocytes, but not spermatogonia, contain the activin beta(A) subunit mRNA and protein. In contrast, gonocytes first expressed follistatin mRNA and protein at 3 days after birth, concordant with the transition of gonocytes to spermatogonia. Collectively, these data demonstrate that germ cells have the potential to regulate their own maturation through production of endogenous activin A and follistatin. Sertoli cells were observed to produce the activin/inhibin beta(A) subunit, the inhibin alpha subunit, and follistatin, demonstrating that these cells have the potential to regulate germ cell maturation as well as their own development. These findings indicate that local regulation of activin bioactivity may underpin the coordinated development of germ cells and somatic cells at the onset of spermatogenesis.

Activins↗

PubMed1984

Testicular exocrine malfunction after torsion.

The exocrine and endocrine functions of the testis were assessed in 67 patients a median of 4.0 years after unilateral torsion (range 3 months-12 years). Of 54 patients who underwent orchidopexy, some atrophy of the affected testis developed in 46; the degree of atrophy was significantly correlated with the duration of torsion (r = -0.56, p less than 0.001). The remaining 13 patients had undergone orchidectomy after a mean duration of torsion of 71 h. Seminal analysis was abnormal in 44 of 51 patients tested (86%), and the low total motile sperm count correlated with the duration of torsion (r = -0.53, p less than 0.001). Sperm counts were much lower in men with torsion for longer than 8 h than those with a shorter period of torsion (median 7.2 X 10(6) v 83.5 X 10(6); p less than 0.00003). Serum levels of luteinising hormone, prolactin, testosterone, and follicle-stimulating hormone were generally within normal limits. An acute ischaemic episode affecting only one testis causes bilateral loss of exocrine function in most patients, while endocrine function is preserved.

Adolescent↗

PubMed1978

Orchiopexy in prepubertal boys. Five-year survey.

A series of 141 prepubertal boys with undescended testes operated on in a provincial teaching hospital has been analyzed five years after operation. The main features noted at presentation were the mature age of the patients and the small number of boys referred by pediatricians. The incidence of unsatisfactory results was 36% in unilateral and 35% in bilateral operations. The majority of the patients (81%) were referred for surgery after the age of five years, commonly regarded as the most suitable time for surgical correction. Three patients required a primary orchiectomy for a small atrophic testis, while 2 patients had an orchiectomy done on a previously operated testis. The complication rate for the series was 4.5%. Testicular biopsy was not done at the time of operation, and no patients were referred for semen analysis. Eight patients underwent a second orchiopexy after the first operation failed. In 6 patients an atrophic testis developed after the second procedure. The need for more than one postoperative examination is stressed in view of the fact that an initially favorable result may not persist since the testes may be found, at a later date, to have retracted into an unsatisfactory position. The reasons for the poor results are discussed and compared briefly with previous reports.

Adolescent↗

PubMedDate not supplied

Influence of thyroid hormone on Sertoli cell protein metabolism in the prepubertal pig.

In order to better understand the role of thyroid hormones in testis development, the influence of tri-iodothyronine on protein metabolism of immature pig Sertoli cells has been investigated. Sertoli cells were isolated enzymatically from 2- to 3-week-old piglet testes and cultured in the presence or absence of tri-iodothyronine. Protein labelling was evaluated in Sertoli cell monolayers incubated in medium containing a tracer dose of [3H]leucine. The results demonstrate that thyroid hormone can directly stimulate the process of protein synthesis in immature porcine Sertoli cells, without significantly affecting the protein degradation rate; moreover thyroid hormone exposure results in a significant decrease of intracellular ATP level. The evidence that tri-iodothyronine can increase Sertoli cell protein synthesis, supplies additional evidence about the fundamental role of thyroid hormone in the regulation of growth and differentiation of the mammalian testis through a direct action on the Sertoli cells.

Adenosine Triphosphate↗

PubMed2006

Neonatal treatment with naloxone increases the population of Sertoli cells and sperm production in adult rats.

Endogenous opioid peptides play an important role in the ontogenesis of the functional and morphological parameters of the seminiferous epithelium. The aim of this study was to evaluate the effects of neonatal manipulations with naloxone, an opioid antagonist, on the population of Sertoli cells and on sperm production in adult rats. Rats were assigned to receive 8 mug per gram of body weight twice a day with interval of 8 h of naloxone and they were compared to a control group receiving saline. Naloxone groups presented the following findings when compared to the control group: increased body weight from the 2nd to the 27th day; a smaller seminiferous epithelium height, smaller seminiferous tubule diameter, increased number of Sertoli cells and daily sperm production per testis, increased daily sperm production per gram per testis and increased total length of the seminiferous tubule of the treated groups. According to our study, the neonatal treatment with naloxone during the critical period of testis development was able to change the proliferative dynamics of Sertoli cells by an intra and/or extra testicular blockage of opioid receptors, confirming the direct relation between the number of Sertoli cells and the number of spermatozoids.

Animals↗

PubMed2000

A 90-kDa glycoprotein exhibited stage-specific expression in meiotic germ cells in rat testes.

We produced a monoclonal antibody, designated MC301, against the extract of testicular cells from 12-day-old rats. This age corresponds to the onset of meiosis during testis development. MC301 specifically recognized a 90-kDa glycoprotein, GP90-MC301, which was ubiquitously expressed in various tissues and localized predominantly in the Golgi area of epithelial cells. In adult testes, stage-specific intense expression of GP90-MC301 was shown in the cytoplasm of meiotic spermatogenic cells from the preleptotene to mid-pachytene stages. Immunoelectron microscopy demonstrated that the glycoprotein was localized in spermatocytes on protein synthesis-related organelles such as the Golgi apparatus, endoplasmic reticulum, and nuclear envelope. The plasma membrane of spermatocytes and the intercellular space surrounding the cells were also immunoreactive. No specific immunoreactivity was found on the organelles in other testicular cells. A considerable amount of the glycoprotein was detected in the extracellular fluid of the testes. These results suggest that GP90-MC301 is produced mainly by spermatocytes in the testis and secreted into the surrounding intercellular space. The evidence for developmentally regulated expression of GP90-MC301 in the meiotic spermatogenic cells suggests a possible role for the glycoprotein in male germ cell meiosis.

Animals↗

PubMed2006

Effect of various photoperiods on testicular weight, weekly sperm output and plasma levels of LH and testosterone over the reproductive season in male turkeys.

The effects of duration and variation in photoperiod on testis weight, testicular sperm production, semen output, and hormone status over the reproductive season in male turkeys were investigated. In Experiment 1, four groups of males raised from 17 to 23 wk of age under a constant short photoperiod were subjected to a constant short (Group 1: 7L:17D; Group 2: 10.5L:13.5D), constant long (Group 3: 14L:10D) or progressively increasing photoperiod (Group 4: 7L:17D to 14L:10D) up to 60 wk of age. In Experiment 2, four groups of males first raised as in Experiment 1 up to 23 wk of age were placed under a constant short (Group 5: 10.5L:13.5D), constant long (Group 6: 14L:10D), or night-interrupted photoperiod (Group 7: 6L:2.5D:1L:14.5D, referred to as subjective 9.5L:14.5D; Group 8: 6L:3.5D:1L:13.5D), referred to as subjective 10.5L:13.5D) up to 60 wk of age. Males in Groups 2-4 had similar reproductive characteristics, whereas sexual maturity was delayed from 29 to 49 wk in males from Group 1. In Experiment 2, males in Groups 5 and 8 had similar reproductive characteristics, whereas sexual maturity was delayed in males in Group 7 in a manner similar to that observed in Group 1. In both experiments, plasma LH and testosterone concentrations were poor indicators of testis development and semen production, irrespective of age and photoperiod. We conclude that a moderately short photoperiod such as 10.5L:13.5D or subjective 10.5L:13.5D may stimulate reproductive characteristics of male turkeys in a manner comparable to constant long or increasing photoperiods. We inferred the existence of a threshold of photosensitivity in male turkeys for photoperiods longer than 9.5L:14.5D, but shorter than or equal to 10.5L:13.5D.

Age Factors↗

PubMed2006

Transgenerational effect of the endocrine disruptor vinclozolin on male spermatogenesis.

The current study was designed to examine the actions of a model endocrine disruptor on embryonic testis development and male fertility. Pregnant rats (F0) that received a transient embryonic exposure to an environmental endocrine disruptor, vinclozolin, had male offspring (F1) with reduced spermatogenic capacity. The reduced spermatogenetic capacity observed in the F1 male offspring was transmitted to the subsequent generations (F2-F4). The administration of vinclozolin, an androgen receptor antagonist, at 100 mg/kg/day from embryonic day 8-14 (E8-E14) of pregnancy to only the F0 dam resulted in a transgenerational phenotype in the subsequent male offspring in the F1-F4 generations. The litter size and male/female sex ratios were similar in controls and the vinclozolin generations. The average testes/body weight index of the postnatal day 60 (P60) males was not significantly different in the vinclozolin-treated generations compared to the controls. However, the testicular spermatid number, as well as the epididymal sperm number and motility, were significantly reduced in the vinclozolin generations compared to the control animals. Postnatal day 20 (P20) testis from the vinclozolin F2 generation had no morphological abnormalities, but did have an increase in spermatogenic cell apoptosis. Although the P60 testis morphology was predominantly normal, the germ cell apoptosis was significantly increased in the testes cross sections of animals from the vinclozolin generations. The increase in apoptosis was stage-specific in the testis, with tubules at stages IX-XIV having the highest increase in apoptotic germ cells. The tubules at stages I-V also had an increase in apoptotic germ cells compared to the control samples, but tubules at stages VI-VIII had no increase in apoptotic germ cells. An outcross of a vinclozolin generation male with a wild-type female demonstrated that the reduced spermatogenic cell phenotype was transmitted through the male germ line. An outcross with a vinclozolin generation female with a wild-type male had no phenotype. A similar phenotype was observed in outbred Sprague Dawley and inbred Fisher rat strains. Observations demonstrate that a transient exposure at the time of male sex determination to the antiandrogenic endocrine disruptor vinclozolin can induce an apparent epigenetic transgenerational phenotype with reduced spermatogenic capacity.

Animals↗

PubMed1993

Mutational analysis of SRY in XY females.

The Y chromosome located gene SRY (sex determining region Y gene) was identified in the search for the mammalian testis determining factor (TDF). Approaches for evaluating SRY as a candidate for TDF included the finding of mutations in SRY in the genomes of patients with failed testis development (XY females or 46,XY gonadal dysgenesis) and the production of female to male sex reversed mice transgenic for the mouse homologue of SRY, [Sry]. Since the initial use of XY females in the proof of SRY/TDF identity, many more patients have been analysed using different techniques and more mutations identified. A total of 11 mutations in SRY have now been described, all in the DNA-binding HMG-box region of the gene, and all in patients with apparently complete gonadal dysgenesis. Surprisingly, three familial SRY mutations have been identified, where the phenotype is either fertile male or sterile sex-reversed female. Estimates of the proportion of XY females mutant for SRY average at approximately 15%. Reasons for the low frequency of SRY mutations in XY sex reversal could be the presence of mutations in regions of SRY not yet discovered, the occurrence of mutations that give the same phenotype, perhaps in genes close to SRY in the testis determining pathway, or incorrect diagnosis of complete gonadal dysgenesis.

Amino Acid Sequence↗

PubMed1998

Transforming growth factor beta1 and beta2 reduce the number of gonocytes by increasing apoptosis.

Transforming growth factors beta1 and beta2 (TGFbetas) have recently been detected by immunohistochemistry in the fetal and neonatal rat testis, and the aim of the present study was to determine whether these factors can act as local regulators to control the number of gonocytes. Testes were kept in organ culture, and TGFbeta1 was found to have dose-dependent inhibitory effect on the number of gonocytes in testes explanted on fetal day 13.5. Either TGFbeta1 or beta2 at 10 ng/ml reduced the number of gonocytes by half after 2 days culture. TGFbetas did not decrease the BrdU labeling index of gonocytes or Sertoli cells, whereas these factors significantly increased the DNA fragmentation in gonocytes (TUNEL method). The other testicular cell types showed no positive TUNEL reaction. TGFbeta1 did not reduce the number of gonocytes in testes explanted on fetal day 17.5 (i.e. during the quiescent phase), but it did so in testes explanted on postnatal day 3 (i.e. stage of resumption of mitosis). To determine the potential cell type targets for TGFbetas, type I and type II TGFbeta receptors were immunolocalized in developing testis from fetal day 13.5 to postnatal day 3. Both receptors were present in the gonocytes throughout the whole period studied, and in the Leydig cells from fetal day 16.5 onward, but they were not detected in the Sertoli cells. Taken together, these results suggest that TGFbetas directly increase apoptosis in gonocytes without changing their mitotic activity during the developmental phases of proliferation.

Aging↗

PubMedDate not supplied

[The effect of prolactin and bromocriptine on testicular incretory function].

Prolactin (PRL) is synthesized by lactotropic pituitary cells. The corresponding hormonal preparations is dispensed as lactin. Bromocriptine is a dopamine agonist, dopamine being a natural inhibitor of PRL-secretion. PRL receptors in the testis are located on the interstitial cells. PRL effect on the testis depends on the age and species of animals. In the immature animals as well as in the photoperiodic ones PRL stimulates the testis development and the testicular secretion; bromocriptine decreases androgen concentration. In the postpubertal animals PRL is a melatonin antagonist in the dark time but LH synergist at the exposure to light. A high PRL concentration inhibits gonadoliberin formation, LH secretion; testosterone concentration and especially dihydrotestosterone concentration decrease (or do not change) with an elevation of estradiol level that on the whole results in feminization. The cerebral transmitters promoting or inhibiting sexual behavior are involved in the interaction with PRL. Administration of PRL, experimental or pathological hyperprolactinemia are followed by the suppression of ejaculation. Bromocriptine (parlodel) appears to be a pathogenetic therapeutic agent in hyperprolactinemia.

Aging↗

PubMed2005

Chromosome chains and platypus sex: kinky connections.

Mammal sex determination depends on an XY chromosome system, a gene for testis development and a means of activating the X chromosome. The duckbill platypus challenges these dogmas.(1,2) Gutzner et al.(1) find no recognizable SRY sequence and question whether the mammalian X was even the original sex chromosome in the platypus. Instead they suggest that the original platypus sex chromosomes were derived from the ZW chromosome system of birds and reptiles. Unraveling the puzzles of sex determination and dosage compensation in the platypus has been complicated by the fact that it has a surplus of sex chromosomes. Rather than a single X and Y chromosome, the male platypus has five Xs and five Ys.

Animals↗