Transplantation Of Testicular Tissue Research Articles

Сравнительная характеристика эффективности профилактики прогрессирования ХПН с использованием терапии секретомом эмбриональных клеток и трансплантации неонатальных тканей.

Introduction. Literature data and our own research indicate that therapy with immature cell secretion products (secretome) has a pronounced nephroprotective effect both in acute kidney injury and in chronic renal failure (CRF). Considering that the source of the complex of signaling molecules stimulating reparative processes in organs are low-differentiated cells of functionally and anatomically immature organs in a state of deveopment, the question arises to what extent tissue transplantation of these organs reproduces the effect of therapy with a secretome of stem cells in relation to the progression of CRF. Material and methods. The experiments were carried out on 40 outbred male rats weighing 260-290 g, in which CRF was modeled by resection of 4/5 functionally active renal parenchyma. In the 1st series (control), no therapeutic actions were performed. In the 2nd series, after modeling CRF, a course of therapy with Cellex, the active component of which is the secretome of pig embryonic brain cells, was carried out in the form of 2 10-day courses with a 10-day break between them. In the 3rd and 4th series, immediately after CRF modeling, kidney or testicle tissue obtained from newborn baby rats (1-2 days after birth) was injected under the capsule of the resected kidney as a source of immature cells. Tissues of different organs were used to assess the severity of the tissue-specific effect of therapy. Results. 7 days after the modeling of CRF in all series, a deterioration of more than 2 times of all functional parameters was revealed. After 1 month, in the control and in the 2nd and 3rd series, a tendency to an increase in GFR was revealed, which did not reach statistical significance, whereas in the 4th series, the increase in GFR turned out to be statistically significant. After 2 months in the control series, there was a repeated decrease in the GFR index, whereas in all experimental series, GFR continued to increase or remained at subnormal values. The activity of tubular reabsorption of sodium and calcium after a significant decrease after 7 days to 1 month in the control series increased slightly (but unreliably), and after 2 months they again decreased to values 2 times lower than normal. In all experimental series, after 1 and 2 months, the reabsorption of these electrolytes was at values close to normal. The improvement was especially pronounced in groups 2 and 4. After 7 days, the activity of intracellular enzymes (aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH)) in the blood increased in all series with a gradual decrease in hyperfermentemia after 2 months, more pronounced in group 4, as well as in all experimental groups with respect to LDH. Histological examination of the condition of neonatal transplants revealed the destruction of transplanted kidney tissue and a viable testicular graft. Conclusion. Transplantation of neonatal organ tissue under a kidney capsule to rats with CRF has a comparable nephroprotective effect with therapy with the secretome of embryonic cells (Cellex drug). A more pronounced improvement in functional parameters during testicular tissue transplantation is explained by the preservation of the viability of the graft.

In vivo and in vitro sperm production: an overview of the challenges and advances in male fertility restoration.

Male infertility can be caused by genetic anomalies, endocrine disorders, inflammation, and exposure to toxic chemicals or gonadotoxic treatments. Therefore, several recent studies have concentrated on the preservation and restoration of fertility to enhance the quality of life for affected individuals. It is currently recommended to biobank the tissue extracted from testicular biopsies to provide a later source of spermatogonial stem cells (SSCs). Another successful approach has been the in vitro production of haploid male germ cells. The capacity of SSCs to transform into sperm, as in testicular tissue transplantation, SSC therapy, and in vitro or ex vivo spermatogenesis, makes them ideal candidates for in vivo fertility restoration. The transplantation of SSCs or testicular tissue to regenerate spermatogenesis and create embryos has been achieved in nonhuman mammal species. Although the outcomes of human trials have yet to be released, this method may soon be approved for clinical use in humans. Furthermore, regenerative medicine techniques that develop tissue or cells on organic or synthetic scaffolds enriched with bioactive molecules have also gained traction. All of these methods are now in different stages of experimentation and clinical trials. However, thanks to rigorous studies on the safety and effectiveness of SSC-based reproductive treatments, some of these techniques may be clinically available in upcoming decades.

Filling the Gaps in Oncofertility Care by Addressing Challenges Faced by Patients and Providers.

With enhanced technology and upcoming treatment strategies in the cancer field, the survival rates of patients have increased. We have now reached a stage in the treatment of cancer where we not only address the disease but also address complications that arise due to the disease and the side effects that present in the post-survival population due to its treatment. One of the primary consequences after oncotherapy is infertility, which is a major reason for distress for patients' post-survival, as they are afraid they may be deemed as less desirable, be rejected by their existing partner, or cannot grapple with the fact that they cannot have children of their own. This can be avoided by the implementation of proper oncofertility practices. The subject of oncofertility involves interactions between experts in the domains of cancer diagnosis, therapy, fertility preservation, and reproductive health. It attempts to investigate and broaden the possibilities for cancer survivors' reproductive future in order to suit their needs according to their ethical religious and sociocultural beliefs. However, these practices are often not implemented effectively due to ineffective doctor-patient communication, lack of knowledge, or partial knowledge of clinicians themselves regarding fertility care. This leads to a feeling of insecurity among clinicians hence resulting in them not referring patients. Lack of awareness among doctors of different oncofertility procedures available especially for patient groups like women and younger patients, hence leading to reduced referral in these groups. Improper coordination across health departments, patient ignorance regarding procedures, financial instability especially in acountrywitha lower sociodemographic indexlike India, and neglect or less importance given to the related ethical, social, and legal issues. In this article, we cover the effects of cancer and cancer treatment on fertility, the options available to adult and pediatric cancer patients to preserve their fertility like oocyte/ovarian tissue cryopreservation in females and sperm cryopreservation in males,techniques undergoing experimental studies that could be implemented in the future like spermatogonial stem culture and transplantation of testicular tissue, the obstacles that we face that hinder the proper implementation of such practices and what measures can we take to overcome these obstacles to improve patient care and be better healthcare providers.

Accelerated and Improved Vascular Maturity after Transplantation of Testicular Tissue in Hydrogels Supplemented with VEGF- and PDGF-Loaded Nanoparticles.

Avascular transplantation of frozen–thawed testicular tissue fragments represents a potential future technique for fertility restoration in boys with cancer. A significant loss of spermatogonia was observed in xeno-transplants of human tissue most likely due to the hypoxic period before revascularization. To reduce the effect of hypoxia–reoxygenation injuries, several options have already been explored, like encapsulation in alginate hydrogel and supplementation with nanoparticles delivering a necrosis inhibitor (NECINH) or VEGF. While these approaches improved short-term (5 days) vascular surfaces in grafts, neovessels were not maintained up to 21 days; i.e., the time needed for achieving vessel stabilization. To better support tissue grafts, nanoparticles loaded with VEGF, PDGF and NECINH were developed. Testicular tissue fragments from 4–5-week-old mice were encapsulated in calcium-alginate hydrogels, either non-supplemented (control) or supplemented with drug-loaded nanoparticles (VEGF-nanoparticles; VEGF-nanoparticles + PDGF-nanoparticles; NECINH-nanoparticles; VEGF-nanoparticles + NECINH-nanoparticles; and VEGF-nanoparticles + PDGF-nanoparticles + NECINH-nanoparticles) before auto-transplantation. Grafts were recovered after 5 or 21 days for analyses of tissue integrity (hematoxylin–eosin staining), spermatogonial survival (immuno-histo-chemistry for promyelocytic leukemia zinc finger) and vascularization (immuno-histo-chemistry for α-smooth muscle actin and CD-31). Our results showed that a combination of VEGF and PDGF nanoparticles increased vascular maturity and induced a faster maturation of vascular structures in grafts.

Гистологическое исследование нативных и криоконсервированных неонатальных семенников крыс после интратестикулярной аллотрансплантации

Cryopreservation and transplantation of testicular fragments and cells are utilized in establishing the germplasm bank of endangered species, line-breeding of animals. Moreover, the transplantation of testicular tissue is involved into investigation of the inborn and acquired defects of testicular tissue. Thus the improvement of cryopreservation and transplantation methods is of great interest. Here, we have compared the findings of histological examination of allotransplanted native and cryopreserved neonatal testis. It has been shown that the usage of DMEM/F12 supplemented with 5 mg/ml bovine serum albumin, 0.05 M sucrose, 20 mM Hepes, 1.5 M dimethylsulfoxide as a cryoprotectant, controlled cooling, preservation at -196°C, water bath warming, followed by intratesticular allotransplantation of neonatal rat testis results in the development of testicular interstitium and spermatogenic epithelium of donor organs into recipient body. Probl Cryobiol Cryomed 2020; 30(1): 34-46

Oncofertility in adult and pediatric populations: options and barriers.

Cancer and its treatments can affect fertility in a variety of ways, and recent advances in cancer detection and treatment have led to an increasing number of cancer survivors for whom future fertility is a primary concern. Oncofertility is the study of interactions between cancer, anti-cancer therapy, fertility, and reproductive health. Fertility preservation aims to optimize fertility potential before initiation of gonadotoxic therapies. Sperm cryopreservation from an ejaculated sample is the gold standard for adults and post-pubertal adolescents, though added maneuvers such as medical therapy, penile vibratory stimulation, and electroejaculation can be employed when appropriate. When all these approaches fail, testicular sperm extraction can be used to obtain and cryopreserve testicular sperm from the azoospermic patient. Fertility preservation in the pre-pubertal pediatric patient is still experimental, but recent scientific breakthroughs with use of spermatogonial stem cells and testicular tissue transplantation offer great promise for the future. While there may be several practical, cultural, religious, and other barriers to fertility preservation, the establishment of a dedicated fertility preservation team can help to overcome these obstacles and optimize the utilization of fertility preservation in cancer patients of all ages.

"How Far Have We Reached with Regards to Our Endeavours in Testicular Tissue Transplantation Along with in Vitro Spermatogenesis After Success in Animals - A Systematic Review”

"How Far Have We Reached with Regards to Our Endeavours in Testicular Tissue Transplantation Along with in Vitro Spermatogenesis After Success in Animals - A Systematic Review”

FERTILITY PRESERVATION: Testicular transplantation for fertility preservation: clinical potential and current challenges.

Transplantation of testicular tissues and cells has been proposed as a future clinical option for patients who have had testicular tissue cryopreserved prior to receiving gonadotoxic therapies. Whilst this approach remains experimental, success using animal models and successful transplantation of ovarian tissue resulting in live births in female patients provides optimism for the development of clinical applications involving transplantation of testicular tissue in males. Careful consideration must be given to patient groups that may benefit from this approach in the future. Current research is focused on optimising patient selection, methods for tissue cryopreservation and development of transplantation techniques that might restore sperm production or future fertility in males. Crucially, attention must be focused on ensuring safety of transplantation, including eliminating the potential for infection or re-introducing malignancy. Furthermore the genetic/epigenetic integrity of any gametes generated must be ensured to allow generation of normal offspring. This review will provide an overview of the current status of transplantation of testicular tissue and cells for fertility preservation in males.

Transplantation of testicular tissue in alginate hydrogel loaded with VEGF nanoparticles improves spermatogonial recovery

Transplantation of cryopreserved immature testicular tissue (ITT) is a promising strategy to restore fertility in young boys facing gonadotoxic treatments. However, up to now, limited spermatogonial recovery has been achieved in xenografting models used to evaluate the potential of cryopreserved tissue transplantation. When comparing avascular xenografts of cryopreserved and fresh human ITT into a mouse model, the number of spermatogonia was significantly reduced, regardless of the cryopreservation procedure used. To improve tissue engraftment, revascularization and hence spermatogonial survival, ITT was embedded in two types of hydrogel loaded with VEGF nanoparticles. Small pieces (±1mm3) of testicular tissue were grafted in NMRI mice as follows: grafted without encapsulation, grafted after encapsulation in fibrin, in alginate, in fibrin-VEGF-nanoparticle (NP) and in alginate-VEGF-NP. Non-grafted tissue served as control. After 5 and 21days of implantation, seminiferous tubule integrity, revascularization and spermatogonial recovery were evaluated by histology and immunohistochemistry. Seminiferous tubule integrity ranged from 13.3% to 39.6% and 42.7% to 68.7% on day 5 and day 21, respectively. Vascular density on day 5 was found to be higher in VEGF supplemented groups, regardless of the hydrogel used. Staining for phosphorylated VEGF receptor 2 and endothelial proliferation on day 5 was higher in all groups compared to non-grafted avascular controls. Spermatogonial recovery ranged between 14.8% and 27.3% on day 21 and was significantly higher in the alginate and alginate-VEGF-NP groups. The present study demonstrates the potential of alginate hydrogel loaded with nanoencapsulated growth factors to improve cryopreserved tissue engraftment.

Production of Live Offspring from Testicular Tissue Cryopreserved by Vitrification Procedures in Japanese Quail (Coturnix japonica)1

Cryopreservation of testicular tissue can be used for ex situ conservation of male germplasm of avian species. The possibility of using vitrification and transplantation of testicular tissue for fertility preservation and recovery was tested in Japanese quail. Testes were removed from 1-wk-old Japanese quail; transfixed on acupuncture needles; equilibrated with dimethyl sulphoxide, ethylene glycol, and sucrose; plunged into liquid nitrogen; and stored in 2-ml straws. Cryopreserved tissue was warmed in sucrose solution at room temperature or at 40°C. Fresh and cryopreserved tissue were transplanted subcutaneously into castrated, 1-wk-old recipients. Twenty of 21 recipients survived the surgery, and 18 had viable transplants at maturity, with no difference in transplantation success between fresh and cryopreserved tissue. Fluid extrusion from 11 of the transplants was collected and inseminated surgically into the magnum of 22 quail hens, and 10 inseminations included foam from the proctodeal gland of the same recipients. Egg production in the 2 wk after insemination was reduced, and none of the hens inseminated with foam produced fertile eggs. Five hens inseminated without foam produced a total of eight live offspring; four of these hens had been inseminated with fluid extrusion from cryopreserved tissue. Histological examination showed spermatogenesis in the transplants, and the tubules, lumens, and epithelium of the seminiferous tubules were of comparable size to those of testicular tissue from intact males. These results demonstrate that testicular tissue of Japanese quail can be preserved using vitrification procedures and recovered through transplantation.

Present and Future Prospects of Male Fertility Preservation for Children and Adolescents

Rapid progress in fertility preservation strategies has led to the investigation of ways in which fertile gametes could be generated from cryopreserved immature testicular tissue. Childhood cancer patients remain the major group that can benefit from these techniques. Other potential candidates include patients undergoing gonadectomy and patients with Klinefelter's syndrome and cryptorchid testes. This review aims to present an overview of the current state of knowledge in experimental germ cell transplantation, testicular tissue transplantation, and germ cell culture as fertility preservation methods for males. We included English articles published in PubMed as well as personal files with the focus on studies including human or nonhuman material. Germ cell and testicular tissue transplantation demonstrate clinical options to mature germ cells from immature primate testicular tissue. The most promising approach involves autologous grafting of immature testicular tissue, whereas germ cell maturation in vitro provides the best strategies to overcome problems of cancer contamination in cryopreserved testicular tissue. Three-dimensional and organ culture systems offer the possibility to differentiate immature male germ cells up to the stage of elongated spermatids. Further characterization of early germ cell development in humans is needed to modify these systems for clinical use.

Heterotopic Transplantation of Testes in Newly Hatched Chickens and Subsequent Production of Offspring via Intramagnal Insemination1

Transplantation of testicular tissue onto the back of immunodeficient nude mice provides a tool to examine testicular development and preserve fertility in mammals. There is no immunodeficient model in birds, but we recently transplanted ovarian tissue between newly hatched chicks from two lines of chickens and produced donor-derived offspring, showing that experimental transplantation is possible in newly hatched chicks. In the present study testicular tissue from newly hatched Barred Plymouth Rock (BPR) chicks was transplanted under the skin of the back, under the skin of the abdomen, or in the abdomen of White Leghorn chicks that had been surgically castrated and immunocompromised. Recipient birds were killed at 10 mo of age. Transplanted tissue was observed in one of five hosts receiving tissue under the skin of the back, two of five hosts receiving tissue under the skin of the abdomen, and three of five chicks with grafts inside the abdominal cavity. In recipients with no regeneration of host testes, testicular transplants grew to the size of normal testes, and histologic analysis showed active spermatogenesis. Subsequent collection of sperm from two successful transplants and surgical insemination of the sperm into the magna of the oviducts of BPR hens resulted in the production of 24 donor-derived chicks. These results demonstrate that the combination of testicular tissue transplantation with intramagnal insemination can produce viable, normal chicks, which could provide a simple approach for the recuperation of live offspring in avian species.

Effect of cold storage and cryopreservation of immature non-human primate testicular tissue on spermatogonial stem cell potential in xenografts

Successful cryopreservation of gonadal tissue is an important factor in guaranteeing the fertility preservation via germ cell or testicular tissue transplantation. The aim of this study was to evaluate the effects of cooling and cryopreservation on spermatogonial stem cell survival and function of immature non-human primate testicular tissue xenografted to nude mice. Group 1 (control group) received subcutaneous grafts of fresh immature rhesus monkey testes. The treatment groups received grafts after 24 h cooling in ice-cold medium (Group 2), after 24 h of cryopreservation without cryoprotectant (Group 3), with ethylene glycol (Group 4: 1.4 M) or with dimethylsulphoxide (DMSO) (group 5: 1.4 M; group 6: 0.7 M), using cooling rates of 0.5 degrees C/min. The graft number, weight and histology were examined 3-5 months later. After xenografting, grafts from fresh and cooled tissue showed good survival and spermatogenic induction to spermatocytes. Cryopreservation in 1.4 M DMSO also allowed grafts to initiate spermatogenesis. In contrast, 0.7 M DMSO and ethylene glycol showed inferior protection. Our observations suggest that cryopreservation of immature primate testis is a feasible approach to maintain spermatogonial stem cells and may serve as a promising tool for fertility preservation of prepubertal boys. The possibility to delay the transplantation of cooled samples suggests an option for clinical centralization of testicular tissue cryopreservation.

Cryoconservation de tissu testiculaire chez le garçon prépubère : indications et faisabilité

Childhood cancers below 15 years old represent almost 2000 new cases each year; their evolution is often favourable since about 75% of children will recover from their cancer. However, the gonad, in particular the testis, is very sensitive to radiotherapy and alkylant agents. Cryopreservation of semen can be proposed to young adults before starting the treatment; the 14-17 years period can be considered as a critical phase, because some boys have not achieved puberty. Thereby semen collection failures are frequent and semen quality is sometimes poor. In prepubertal boys, testicular stem cell banking is the only way of preserving the future fertility. Transplantation of testicular tissue was tempted for the first time in 1994: recipient mice produced gametes derived from testicular stem cells of donor mice, and could produce transgenic offspring. However, in the mouse, births after transplantation of cryopreserved stem cells were obtained only recently, in 2003. A lot of questions remain uncompletely resolved in animal models and of course in humans: stem cells enrichment, freezing-thawing protocols, transplantation procedure and corresponding health risks, represented by the possible re-introduction of malignant cells. Xenotransplantation or in vitro maturation of spermatogonia after thawing the testicular tissue could represent an alternative permitting to obtain malignant cell-free spermatozoa. However, a complete spermatogenesis in vitro has not yet been obtained, in any species.

豚の無血去勢 (ボールマッシャー法) によって生じた精巣組織の腹腔内移植について

豚の無血去勢 (ボールマッシャー法) によって生じた精巣組織の腹腔内移植について

The effects of testosterone on the connective tissue of the comb of the cockerel.

The growth of the cock’s comb has long been known to be dependent upon stimulation by androgens (Champy and Kritch, 1925; Hardesty, 1931). By virtue of this reaction the combs of the capon and chick have been used extensively for the bioassay of male hormones. Remarkably, however, there has been little attempt to analyze the structural changes in this response. In 1925–26, Champy and Kritch published the first histological descriptions of the comb of the chicken. They identified a “mucoelastic” layer in this organ, consisting of loose connective tissue in which there were abundant elastic fibers and many large vacuoles filled with mucoid material. They claimed that complete disappearance of this layer occurred after castration, and that it reappeared after intraperitoneal transplantation of testicular tissue. Hardesty (1931) published a more detailed histologic description, in which she subdivided the comb into several anatomic layers. We have confirmed her findings and have adhered to her terminology throughout.

Die Wechseljahre des Mannes.

In this monograph Hoche takes a stand against the assumption of some authors that there exists a sexual climacteric stage in men similar to the climacterium in women. After having thoroughly considered the somatology and symptomatology subsequent to the elimination of the ovarian functions, the author quotes in full the literature dealing with the existence of a climacteric stage in men. From his point of view, all these assertions are based on erroneous interpretation. There is no change in aging men that could not satisfactorily be explained by the prevailing general senile degeneration without referring to any changes in the gonads. These considerations, according to the author, furnish a theoretical basis for the failure of the attempts to influence favorably the senile decay by the Steinach operation or by the transplantation of testicular tissue.