Effect of donor age on success of spermatogenesis in feline testis xenografts

2007 ◽  
Vol 19 (7) ◽  
pp. 869 ◽  
Author(s):  
Yeunhee Kim ◽  
Vimal Selvaraj ◽  
Budhan Pukazhenthi ◽  
Alexander J. Travis

Ectopic xenografting of ‘donor’ feline testicular tissue into a ‘recipient’ immunodeficient mouse is a promising tool to preserve the male genome from genetically valuable felids. To define parameters under which the technique can succeed, we compared the effect of donor age on xenograft spermatogenesis among four age groups of domestic cats (Felis catus; age range 8 weeks to 15 months). In all cases, fresh tissue was grafted into castrated mice and collected 10, 30 and 50 weeks later. The percentage of xenografts recovered decreased as donor age increased. Mature testicular spermatozoa were observed in xenografts from the 8 and 9–16 week age groups; only a single 7-month-old donor produced elongating spermatids and xenografts from donors ≥ 8 months of age degenerated. Seminal vesicle weight, an indicator of bioactive testosterone, was not significantly different between donors aged 8 weeks to 7 months and controls, suggesting that xenograft Leydig cells were ultimately functional even in the 5–7 month age group. Regardless of donor age, production of mature spermatozoa from xenografts was markedly delayed compared with controls. Comparison of xenografts that produced sperm with normal controls revealed a decrease in tubule cross-sections having post-meiotic germ cells. Together, these results indicate that the maximum practical donor age was just before the onset of puberty and that even successful xenografts had abnormalities in spermatogenesis.

1974 ◽  
Vol 60 (3) ◽  
pp. 653-663 ◽  
Author(s):  
Akitsugu Saito ◽  
Murray Smigel ◽  
Sidney Fleischer

There have been several reports describing paracrystalline arrays in the intermembrane space of mitochondria. On closer inspection these structures appear to be junctions of two adjoining membranes. There are two types. They can be formed between the outer and inner mitochondrial membranes (designated outer-inner membrane junctions) or between two cristal membranes (intercristal membrane junctions). In rat heart, adjoining membranes appeared associated via a central dense midline approximately 30 Å wide. In rat kidney, the junction had a ladder-like appearance with electron-dense "bridges" approximately 80 Å wide, spaced 130 Å apart, connecting the adjoining membranes. We have investigated the conditions which favor the visualization of such structures in mitochondria. Heart mitochondria isolated rapidly from fresh tissue (within 30 min of death) contain membrane junctions in approximately 10–15% of the cross sections. This would indicate that the percentage of membrane junctions in the entire mitochondrion is far greater. Mitochondria isolated from heart tissue which was stored for 1 h at 0°–4°C showed an increased number of membrane junctions, so that 80% of the mitochondrial cross sections show membrane junctions. No membrane junctions are observed in mitochondria in rapidly fixed fresh tissue or in mitochondria isolated from tissue disrupted in fixative. Thus, the visualization of junctions in the intermembrane space of mitochondria appears to be dependent upon the storage of tissue after death. Membrane junctions can also be observed in mitochondria from other stored tissues such as skeletal muscle, kidney, and interstitial cells from large and small intestine. In each case, no such junctions are observed in these tissues when they are fixed immediately after removal from the animal. It would appear that most studies in the literature in which isolated mitochondria from tissues such as heart or kidney were used were carried out on mitochondria which contained membrane junctions. The presence of such structures does not significantly affect normal mitochondrial function in terms of respiratory control and oxidative phosphorylation.


Endocrinology ◽  
2008 ◽  
Vol 149 (10) ◽  
pp. 5288-5296 ◽  
Author(s):  
Rahul Rathi ◽  
Wenxian Zeng ◽  
Susan Megee ◽  
Alan Conley ◽  
Stuart Meyers ◽  
...  

In juvenile monkeys, precocious puberty can be induced by administration of gonadotropins resulting in testicular somatic cell maturation and germ cell differentiation. It is, however, unknown whether testicular maturation can also be induced in younger monkeys. Here we used testis tissue xenografting to investigate whether infant monkey testis tissue will undergo somatic cell maturation and/or spermatogenesis in response to endogenous adult mouse gonadotropins or exogenous gonadotropins. Testicular tissue pieces from 3- and 6-month-old rhesus monkeys were grafted to immunodeficient, castrated mice. Recipient mice were either left untreated or treated with pregnant mare serum gonadotropin and/or human chorionic gonadotropin twice weekly and were killed 28 weeks after grafting. Testicular maturation in grafted tissue was assessed based on morphology and the most advanced germ cell type present and by immunohistochemistry for expression of proliferating cell nuclear antigen, Mullerian-inhibiting substance, and androgen receptor. Testis grafts, irrespective of donor age or treatment, contained fewer germ cells than donor tissue. Grafts from 6-month-old donors showed tubular expansion with increased seminiferous tubule diameter and lumen formation, whereas those harvested from gonadotropin-treated mice contained elongated spermatids. Grafts from 3-month-old donors recovered from gonadotropin-treated mice contained pachytene spermatocytes, whereas those recovered from untreated mice showed only slight tubular expansion. Immunohistochemistry revealed that exposure to exogenous gonadotropins supported Sertoli cell maturation, irrespective of donor age. These results indicate that sustained gonadotropin stimulation of immature (<12 months old) monkey testis supports Sertoli cell maturation, thereby terminating the unresponsive phase of the germinal epithelium and allowing complete spermatogenesis in testis tissue from infant rhesus monkeys.


Author(s):  
Marco Recenti ◽  
Carlo Ricciardi ◽  
Kyle Edmunds ◽  
Deborah Jacob ◽  
Monica Gambacorta ◽  
...  

Aging well is directly associated to a healthy lifestyle. The focus of this paper is to relate individual wellness with medical image features. Non-linear trimodal regression analysis (NTRA) is a novel method that models the radiodensitometric distributions of x-ray computed tomography (CT) cross-sections. It generates 11 patient-specific parameters that describe the quality and quantity of muscle, fat, and connective tissues. In this research, the relationship of these 11 NTRA parameters with age, physical activity, and lifestyle is investigated in the 3,157 elderly volunteers AGES-I dataset. First, univariate statistical analyses were performed, and subjects were grouped by age and self-reported past (youth–midlife) and present (within 12 months of the survey) physical activity to ascertain which parameters were the most influential. Then, machine learning (ML) analyses were conducted to classify patients using NTRA parameters as input features for three ML algorithms. ML is also used to classify a Lifestyle index using the age groups. This classification analysis yielded robust results with the lifestyle index underlying the relevant differences of the soft tissues between age groups, especially in fat and connective tissue. Univariate statistical models suggested that NTRA parameters may be susceptible to age and differences between past and present physical activity levels. Moreover, for both age and physical activity, lean muscle parameters expressed more significant variation than fat and connective tissues.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Takahisa Hiramitsu ◽  
Kiyomi Ohara ◽  
Toshihide Tomosugi ◽  
Kenta Futamura ◽  
Manabu Okada ◽  
...  

Abstract Background and Aims Although elderly living donors are recognized as a marginal donor for kidney transplantation, the number of elderly living donors are increasing because of insufficiency. We investigated the impact of donor age on living donor kidney transplantation. Method A total 858 adult living donor kidney transplantation (LDKT) between January 2008 and December 2018 was included in this study and followed up until September 2020. LDKTs were stratified into 3 groups according to the donor age; 157 LDKTs from donors aged 30 – 49, 592 LDKTs from donors aged 50 – 69, and 109 LDKTs from donors aged 70 – 89. To investigate the impact of donor age on living donors, postoperative estimated glomerular filtration rates (eGFR), mortality rate and incidence of end stage renal disease were compared between 3 donor age groups. To investigate the impact of donor age on recipients, postoperative eGFR was compared between 3 donor age groups and the risk factors of graft loss were analyzed using Cox regression hazard model. Results The eGFRs of donors demonstrated a decline with increased donor age and significant differences at all time points among 3 donor age groups. (Figure 1) Mortality rate and incidence of end stage renal disease of donors were similar among 3 donor age groups. (Figure 2) The eGFRs of recipients demonstrated a decline with increased donor age and significant differences at all time points among 3 donor age groups. (Figure 3) Multivariate analysis using Cox regression hazard model demonstrated donor aged 70 – 89 as a significant risk of graft loss (P = 0.024, hazard ratio 3.053, 95% confidence interval 1.160 – 8.040). Conclusion The prognosis of living donors after donation were not affected by the donor age except for the lower eGFR with increased donor age. The eGFRs of recipients and graft loss rates were the worst in the recipients transplanted from donors aged 70 – 89.


2001 ◽  
Vol 12 (7) ◽  
pp. 1538-1546
Author(s):  
JOHAN W. DE FIJTER ◽  
MARKO J. K. MALLAT ◽  
ILIAS I. N. DOXIADIS ◽  
JAN RINGERS ◽  
FRITS R. ROSENDAAL ◽  
...  

Abstract. Donor age was identified recently as a major factor that determines long-term outcome after transplantation, but the mechanism that is responsible for increased graft loss of old donor kidneys is unknown. The influence of donor age on graft survival was assessed retrospectively in 514 consecutive first cadaveric transplants that were treated with cyclosporine maintenance immunosuppression. Donor age ≥50 yr (relative risk [RR] = 1.7; 95% confidence interval [CI], 1.2 to 2.6), acute rejection (RR = 2.0; 95% CI, 1.3 to 3.0), and type of rejection (RR = 3.3; 95% CI, 2.0 to 5.3) had a significant impact on graft survival. However, when subsets of patients who entered subsequent intervals after transplantation were analyzed, donor age was not an independent predictive factor of graft loss. Donor age (RR = 1.53; 95% CI, 1.19 to 1.98), human leukocyte antigen-DR mismatch (RR = 2.28; 95% CI, 1.78 to 2.92), and recipient age (RR = 1.34; 95% CI, 1.05 to 1.72) were associated significantly with acute rejection episodes. Delayed graft function alone was not associated independently with the occurrence of early acute rejection (RR = 1.24; 95% CI, 0.96 to 1.61). The timing of the rejection episodes of old donor kidneys was not different, and the excess rejection prevalence was attributable entirely to interstitial (grade I) types of rejection. Interstitial rejection episodes in kidneys from old donors had a significant (P< 0.05) negative impact on graft survival. Beyond the first year, poor renal function and proteinuria were significant risk factors for graft loss, regardless of rejection. Our data fit best the hypothesis that increased graft loss of older donor kidneys results from an increased incidence of acute interstitial rejection episodes in the early posttransplantation months. It is proposed that kidneys from older donors are more immunogenic than kidneys from young donors and that acute rejection episodes result in functional deterioration. Contrary to interstitial rejection in kidneys from younger donors, kidneys from old donors seem to have an impaired ability to restore tissue.


2011 ◽  
Vol 23 (1) ◽  
pp. 232
Author(s):  
M. Matthiesen ◽  
H. D. Reichenbach ◽  
F. A. Habermann ◽  
M. Reichenbach ◽  
G. J. Arnold ◽  
...  

Recent findings on oogenesis, folliculogenesis, and ovarian aging in cows make the bovine system an attractive model for elucidating ovarian function and dysfunction as well as reproductive aging in women. The aim of the present study was to investigate the influence of donor age on the developmental competence of in vitro v. in vivo matured bovine cumulus–oocyte complexes (COC) obtained by ultrasound-guided repeated ovum pickup (OPU). Two groups (G1 and G2) of German Simmental heifers (14 months old at the beginning of the experiment, n = 5 and n = 7), first-lactation young cows (2–4 y old, n = 5 and n = 3), and old cows (10–15 y old, n = 5 and n = 3) were subjected to twice-weekly OPU without hormonal prestimulation 32 (G1) and 6 times (G2). Afterward, animals in G1 were punctured at 5-week intervals 9 times after FSH superstimulation to obtain in vivo matured COC at the metaphase II stage. Data were analysed using a mixed model (SAS). In the twice-weekly OPU for G1 and G2 combined, significantly (P < 0.05) more COC per animal and OPU session were obtained from the old cows (9.9 ± 1.0) compared with heifers and young cows (6.0 ± 0.8 and 7.0 ± 1.0, respectively). When G1 and G2 were regarded separately, lower numbers of COC (P < 0.01) were obtained in G1 than in G2 (2.7 ± 0.8, 4.4 ± 0.8, 7.0 ± 0.8 and 9.2 ± 1.5, 9.4 ± 2.3, 12.9 ± 2.3 for heifers, young cows, and old cows of G1 and G2, respectively). Cleavage rates (CR) on day 3 after IVF (day 0) were not affected by donor age and were not different between groups. Cultivation of COC from young cows in G1 led to higher blastocyst rates (BR) on day 7 (P < 0.05) compared with old cows and heifers. No differences in BR were observed between animals of G2. Significantly more COC (P < 0.01) were obtained in all age groups from FSH superstimulated donors (10.6 ± 0.8, 9.0 ± 0.9, and 11.7 ± 0.9 for heifers, young cows, and old cows, respectively). Cleavage rates and BR were significantly higher (P < 0.05) in all age groups after FSH superstimulation compared with those of nonstimulated donors. However, there were no differences in CR and BR between age groups (CR: 82.8 ± 7.0, 89.9 ± 7.0, 77.1 ± 6.2%; BR: 34.4 ± 7.2, 44.6 ± 7.2, 36.7 ± 7.2%). We conclude that although the numbers of COC obtained per animal and session were significantly different between G1 and G2, in vitro results were highly repeatable after OPU without hormonal prestimulation. Higher CR and BR were obtained after IVF of in vivo matured COC obtained from FSH superstimulated donors, regardless of animal age. This work was supported by the Deutsche Forschungsgemeinschaft (FOR 1041).


2018 ◽  
Vol 30 (1) ◽  
pp. 233
Author(s):  
M. C. Gomez ◽  
Y. Cates ◽  
D. B. Stansfield ◽  
C. Young ◽  
R. Klee ◽  
...  

Spermatogonial stem cells (SSC) have been isolated from testicular tissue (TT) of several mammalian species and differentiated into mature spermatozoa following transplantation or in vitro culture. The northern white rhinoceros (NWR; Ceratotherium simum cottoni) is critically endangered. Thus, frozen NWR TT, cryopreserved and stored at the San Diego Zoo’s Frozen Zoo®, potentially contain SSC that could be a source of spermatozoa. The method used for cryopreserving TT may affect the integrity and number of SSC. Therefore, identifying alterations in the seminiferous tubules (ST) of frozen-ndash;thawed-NWR TT will provide insight into the condition of the SSC. Therefore, our aims were to (1) determine the effect of freezing rhinoceros TT on the structure of epithelium, and (2) identify SSC (GFRα1, GPR125) and pluripotent (SSEA-4 and Oct-4) markers. Testicular tissue of an adult NWR and a stillborn southern white rhinoceros (SWR) were frozen by equilibration of TT for 30 min at 4.0°C in PBS and 1.5 M dimethyl sulfoxide (DMSO), cooled at 2.0°C/min to −4.0°C, 0.3°C/min to −40°C, and plunged into liquid nitrogen. Tissues were thawed at 37°C in a water bath and DMSO removed in a 4-step dilution. Tissue was then fixed, dehydrated, and paraffin embedded. For morphological evaluations, frozen-ndash;thawed tissue was sectioned and stained with hematoxylin and eosin (H&E). The TT from both rhinoceros collected immediately after death (fresh) and stained with H&E were used as a control for cryopreservation. Localization of SSC and pluripotent markers in ST of frozen-ndash;thawed TT was detected by immunohistochemistry. Morphologically, fresh-NWR TT was severely altered, displaying large epithelium gaps and partial (62.2%) or total detachment (37.7%) from, and slight damage (35.5%) to, the basement membrane. The number of pyknotic nuclei per ST was moderate (15.6 ± 7.2%). Many of these changes could have resulted from autolysis and handling before tissue preparation. In contrast, histological appearance of fresh-SWR was good, with 98.3% of the tubules intact, and a small proportion of pyknotic cells (0.8 ± 1.5%). Seminferous tubule (n = 30/male) length and width (μm; ± SEM) differed between NWR (635.2 ± 34.4 × 214.6 ± 10.8) and SWR (277.7 ± 13.8 × 73.2 ± 2.4; P < 0.05). Damages after cryopreservation compared with fresh tissue comprised (1) epithelium detachment, NWR = 100% (P < 0.0001), and SWR = 43.3% (P < 0.001); (2) basement membrane alteration, only in NWR (93.0%; P < 0.001); and (3) decreased length and width in the ST, NWR = 409.4 ± 18.1 × 173.4 ± 8.2 (P < 0.05), and SWR = 195.2 ± 8.3 × 61.6 ± 2.8 (P < 0.05), with loss of lumen in both males. Immunohistochemistry revealed that NWR expressed GFRα1 and GPR125 at various stages of spermatogenqaesis, whereas Oct-4 was detected in few cells. In contrast to NWR, Oct-4 expression in SWR was located at the basement membrane; SSEA-4 was not detected in either male. In conclusion, freezing-induced morphological alterations in rhinoceros ST and positive expression of markers for SSC and pluripotency suggest the presence of SSC. Further studies are required to evaluate the viability of rhinoceros SSC.


2019 ◽  
Author(s):  
Davide Diena ◽  
Maria Messina ◽  
Consuelo De Biase ◽  
Fabrizio Fop ◽  
Edoardo Scardino ◽  
...  

Abstract Background Proteinuria after kidney transplantation portends a worse graft survival. However the magnitude of proteinuria related to patient and graft survival and its correlation with donor and recipient characteristics are poorly explored. Methods This study investigated the impact of post transplant proteinuria in the first year in 1127 kidney transplants analyzing the impact of different donor ages. Proteinuria cut off was set at 0.5 g/day. Results Transplants with proteinuria > 0.5 g/day correlated with poor graft and patient outcome in all donor age groups. In addition, 6-month-1-year proteinuria increase was significantly associated with graft outcome, especially with donors > 60 years old (p < 0.05; Odd Ratio 1.8). 1-year graft function (eGFR < or ≥44 ml/min) had similar impact to proteinuria (≥ 0.5 g/day) on graft failure (HR 2.77 vs HR 2.46). Low-grade proteinuria (0.2-0.5 g/day) demonstrated a trend for worse graft survival with increasing donor age. Also in kidney-paired analysis proteinuria ≥ 0.5 effect was more significant with donors >50 years old (OR 2.3). Conclusions Post-transplant proteinuria was increasingly harmful with older donor age. Proteinuria ≥ 0.5 g/day correlates with worse outcomes in all transplanted patients. Prognostic value of proteinuria and eGFR for graft and patient survival was comparable and these two variables remain significant risk factors even in a multivariate model that take into consideration the most important clinical variables (donor age, rejection, delayed graft function and cytomegalovirus viremia among others).


Sign in / Sign up

Export Citation Format

Share Document