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Sterile Testis Complementation with Spermatogonial Lines Restores Fertility to DAZL-Deficient Rats and Maximizes Donor Germline Transmission  [PDF]
Timothy E. Richardson, Karen M. Chapman, Christina Tenenhaus Dann, Robert E. Hammer, F. Kent Hamra
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0006308
Abstract: Despite remarkable advances in assisted reproductive capabilities ~4% of all couples remain involuntarily infertile. In almost half of these cases, a lack of conception can in some measure be attributed to the male partner, wherein de novo Y-chromosomal deletions of sperm-specific Deleted-in-Azoospermia (DAZ) genes are particularly prevalent. In the current study, long-term cultures of rat spermatogonial stem cells were evaluated after cryo-storage for their potential to restore fertility to rats deficient in the DAZ-like (DAZL) gene. Detailed histological analysis of DAZL-deficient rat testes revealed an apparently intact spermatogonial stem cell compartment, but clear failure to produce mature haploid gametes resulting in infertility. After proliferating >1 million-fold in cell number during culture post-thaw, as few as 50,000 donor spermatogonia transplanted into only a single testis/recipient effectively restored fecundity to DAZL-deficient rats, yielding 100% germline transmission to progeny by natural mating. Based on these results, the potency and efficacy of this donor stem cell line for restoring fertility to azoospermic rodents is currently unprecedented. Prospectively, similar successes in humans could be directly linked to the feasibility of obtaining enough fully functional spermatogonial stem cells from minimal testis biopsies to be therapeutically effective. Thus, regeneration of sperm production in this sterile recipient provides an advanced pre-clinical model for optimizing the efficacy of stem cell therapies to cure a paradoxically increasing number of azoospermic men. This includes males that are rendered infertile by cancer therapies, specific types of endocrine or developmental defects, and germline-specific de novo mutations; all of whom may harbor healthy sources of their own spermatogonial stem cells for treatment.
Tolnidamine-Induced Changes in the Testis, Sperm Count,Fertility and Accessory Sex Glands of the Laboratory Mouse
Poonam Singh
International Journal of Fertility & Sterility , 2008,
Abstract: Background: Tolnidamine-induced changes have been reported earlier on spermatogenesis, fertilityand sperm count in rat, rabbit and langur monkey. The aim of this study is to assess the response ofthese aspects to tolnidamine in the laboratory mouse.Materials and Methods: Adult male mice (12-14 weeks old) of Parkes (P) strain were used inthe present study. All the animals were divided into five groups. Groups I, II and V were takenas untreated, vehicle-treated initial and vehicle-treated terminal controls, respectively. Meanwhile,animals of Group III were administered with tolnidamine (100mg/kg BW, twice a week) orally for3, 5 and 7 weeks and killed 24 hrs. after the last injection. Animals of Group IV were administeredwith the same dose of the tolnidamine for 7 weeks and then sacrificed 5 and 7 weeks after withdrawalof the drug. Tolnidamine-induced changes were evaluated on spermatogenesis, motility and countof epididymal spermatozoa, fertility and accessory sex glands and compared with the untreated andvehicle-treated controls.Results: Tolnidamine treatment induced significant decrease in the weights of the testis andepididymis; however, the weights of the accessory sex glands remained unaltered following thetreatment. Duration-dependent degenerative changes were noticed in the testicular germinalepithelium showing vacuolization and loosening of the germ cells and Sertoli cells. Percentagemotility and count of epididymal spermatozoa declined significantly following administration oftolnidamine. Likewise fertility of the treated males as well as number of the live blastocysts infemales impregnated with such males also exhibited a significant decrease when compared with thecontrols. However, no change was noticed in the mating ability of the mice treated with tolnidamine.The level of seminal vesicular fructose also remained unaltered after the treatment. Withdrawalstudies revealed duration-dependent recovery in spermatogenesis, percentage motility and count ofspermatozoa and fertility.Conclusion: The findings of the present study, therefore, reveal that tonidamine administration inP mice induces reversible inhibition of spermatogenesis, motility and count of spermatozoa andfertility without affecting the androgen-dependent parameters.
Gadd45g Is Essential for Primary Sex Determination, Male Fertility and Testis Development  [PDF]
Heiko Johnen, Laura González-Silva, Laura Carramolino, Juana Maria Flores, Miguel Torres, Jesús M. Salvador
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0058751
Abstract: In humans and most mammals, differentiation of the embryonic gonad into ovaries or testes is controlled by the Y-linked gene SRY. Here we show a role for the Gadd45g protein in this primary sex differentiation. We characterized mice deficient in Gadd45a, Gadd45b and Gadd45g, as well as double-knockout mice for Gadd45ab, Gadd45ag and Gadd45bg, and found a specific role for Gadd45g in male fertility and testis development. Gadd45g-deficient XY mice on a mixed 129/C57BL/6 background showed varying degrees of disorders of sexual development (DSD), ranging from male infertility to an intersex phenotype or complete gonadal dysgenesis (CGD). On a pure C57BL/6 (B6) background, all Gadd45g?/? XY mice were born as completely sex-reversed XY-females, whereas lack of Gadd45a and/or Gadd45b did not affect primary sex determination or testis development. Gadd45g expression was similar in female and male embryonic gonads, and peaked around the time of sex differentiation at 11.5 days post-coitum (dpc). The molecular cause of the sex reversal was the failure of Gadd45g?/? XY gonads to achieve the SRY expression threshold necessary for testes differentiation, resulting in ovary and Müllerian duct development. These results identify Gadd45g as a candidate gene for male infertility and 46,XY sex reversal in humans.
Facioscapulohumeral Dystrophy: Incomplete Suppression of a Retrotransposed Gene  [PDF]
Lauren Snider equal contributor,Linda N. Geng equal contributor,Richard J. L. F. Lemmers,Michael Kyba,Carol B. Ware,Angelique M. Nelson,Rabi Tawil,Galina N. Filippova,Silvère M. van der Maarel,Stephen J. Tapscott ,Daniel G. Miller
PLOS Genetics , 2010, DOI: 10.1371/journal.pgen.1001181
Abstract: Each unit of the D4Z4 macrosatellite repeat contains a retrotransposed gene encoding the DUX4 double-homeobox transcription factor. Facioscapulohumeral dystrophy (FSHD) is caused by deletion of a subset of the D4Z4 units in the subtelomeric region of chromosome 4. Although it has been reported that the deletion of D4Z4 units induces the pathological expression of DUX4 mRNA, the association of DUX4 mRNA expression with FSHD has not been rigorously investigated, nor has any human tissue been identified that normally expresses DUX4 mRNA or protein. We show that FSHD muscle expresses a different splice form of DUX4 mRNA compared to control muscle. Control muscle produces low amounts of a splice form of DUX4 encoding only the amino-terminal portion of DUX4. FSHD muscle produces low amounts of a DUX4 mRNA that encodes the full-length DUX4 protein. The low abundance of full-length DUX4 mRNA in FSHD muscle cells represents a small subset of nuclei producing a relatively high abundance of DUX4 mRNA and protein. In contrast to control skeletal muscle and most other somatic tissues, full-length DUX4 transcript and protein is expressed at relatively abundant levels in human testis, most likely in the germ-line cells. Induced pluripotent (iPS) cells also express full-length DUX4 and differentiation of control iPS cells to embryoid bodies suppresses expression of full-length DUX4, whereas expression of full-length DUX4 persists in differentiated FSHD iPS cells. Together, these findings indicate that full-length DUX4 is normally expressed at specific developmental stages and is suppressed in most somatic tissues. The contraction of the D4Z4 repeat in FSHD results in a less efficient suppression of the full-length DUX4 mRNA in skeletal muscle cells. Therefore, FSHD represents the first human disease to be associated with the incomplete developmental silencing of a retrogene array normally expressed early in development.
Testis Sparing Surgery For Epidermoid Cyst of Testis in an Infertile Man
Parlakta?, B., S.,K?seo?lu, R., D.,Uluocak, N.,Erdemir, F.
Erciyes Medical Journal , 2005,
Abstract: In this case report, testis sparing surgery, performed for a heterogenous testicular mass in a 25 year-old man was presented. The patient was infertile for five years. Preoperative ultrasound findings allowed us to such surgery. Intraoperative frozen sectioning showed the benign nature of the lesion, consistent with the final histologic examination. For aesthetic, cosmetic, psychologic and fertility preserving benefits, treatment selection of testis sparing surgery in some testicular masses should be carried out according to clinical, radiological and frozen section findings.
PRENATAL TORSION OF TESTIS: A RARE EMERGENCY  [PDF]
Neha Singh Shrivastava,Chandrasekhar Gopalaswamy,Ram Mohan Chivukula Venugopal
Journal of Neonatal Surgery , 2012,
Abstract: Prenatal torsion of testis is an extremely rare surgical emergency with controversial management guidelines. Controversy exists not only with regard to timing and necessity of exploration but also whether or not to fix the contralateral testis as there is no predisposing anatomical defect. Though not life-threatening, it risks fertility of an otherwise healthy newborn male if overlooked. We describe a case of prenatal testicular torsion and discuss pertinent issues.
TORSION OF TESTIS
Irfan Akhtar
The Professional Medical Journal , 1995,
Abstract: A retrospective study of thirty two patients presenting to Emergency department of Rawalpindi General Hospitalwith acute scrotal pain, all being subjected to surgery. Seventeen (54%) were found to have gangrenous testiswith mean time of presentation 9 hours. Nine (28%) patients could be salvaged with bilateral fixation. Seven(22%) were found to have torsion of appendix testis with mean time of presentation being 18 hours. Torsionin undescended testis was encountered in seven (22%) patients. Six(19%) patients had negative explorationsand all were above 25 years of age.
Effect of Formaldehyde Injection in Mice on Testis Function  [PDF]
Tootian Zahra,Tajik Parviz,Fazelipour Simin,Taghva Mehdi
International Journal of Pharmacology , 2007,
Abstract: The medical use of formaldehyde has focused especially on laboratory use. Harmful effects of formaldehyde injection, such as testicular tissue, are quite well documented. However, detailed studies of the effects of formaldehyde on testis functions are quite limited. For this study a total number of 150 mice (60 male and 90 female) were used. Five groups of male mice (n = 6) were subjected to intra peritoneal treatment of formaldehyde daily at doses of 0, 2.5, 5, 7.5 and 10 mg kg-1 body weight in a period of 40 days. From each group 3 male mice were chosen for fertility rate. The results showed that the formaldehyde could exert a significant effect on body weight, gonado-somatic-index, fertility, motility and viability of sperm in all treated groups, but no significant decline of serum testosterone concentration, daily sperm production and testis weight were observed in the same groups. The data suggest that the formaldehyde could affect some of the testis function.
Primary melanoma of testis
Katiyar R,Singh Abhishek,Kumar Deepak
Journal of Cancer Research and Therapeutics , 2008,
Abstract: Primary melanoma of testis is extremely rare and even the existence of such an entity is questioned. We present the case of a 60-year-old man with primary malignant melanoma in the testis. We report this case to emphasize the need for awareness of the possibility of the testis being the primary site in the patient with a melanoma and to underline the necessity of meticulous investigation of suspicious lesions of the testis in patients with or without a past history of malignant melanoma.
Undescended testis in Spigelian hernia  [cached]
Ravi Kumar V,Singal Arbinder
Journal of Indian Association of Pediatric Surgeons , 2007,
Abstract: Spigelian hernias are uncommon in children. We report a 3-year-old boy with right spigelian hernia and right undescended testis. The hernial sac contained the testis, which is a rare presentation. The repair of the large defect with a prosthetic mesh and a concomitant orchidopexy were performed uneventfully.
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