305 OPTIMIZING DONOR AND RECIPIENT FACTORS IN XENOGRAFTING OF TESTIS TISSUE

2010 ◽  
Vol 22 (1) ◽  
pp. 308
Author(s):  
S. Abbasi ◽  
A. Honaramooz
Keyword(s):  
Recipient Mouse ◽  
Male Mice ◽  
Intact Female ◽  
Intact Male ◽  
Immunodeficient Mice ◽  
Female Nude ◽  
Graft Weight ◽  
And Gender ◽  
Gonadal Status ◽  
Testis Tissue

Grafting of donor mammalian testis tissue into recipient mice allows completion of spermatogenesis in the grafted tissue and therefore can serve as a new option for preservation of male germ line. For testis tissue xenografting, castrated male nude mice typically serve as recipients, each receiving 8 testis tissue fragments; however, no study has comprehensively investigated donor and recipient factors. The objective of this study was to determine the effects of strain of immunodeficient recipient mouse (nude v. SCID), gonadal status (intact v. gonadectomized), and gender (male v. female) on the outcome of testis tissue xenografting. A secondary objective was to determine the optimal number of testis tissue fragments per mouse most suitable for xenografting. Testis parenchyma from newborn piglets were cut into small fragments (5 mg each) and grafted under the back skin of different groups of immunodeficient mice. In Experiment 1, 8 groups of mice (n = 7/group) served as recipients: castrated male nude, intact male nude, ovariectomized female nude, intact female nude, castrated male SCID, intact male SCID, ovariectomized female SCID, and intact female SCID. In Experiment 2, 4 groups of mice (n = 10/group) served as recipients of 2, 4, 8, or 16 testis tissue fragments per mouse. Recipient mice were sacrificed 8 months after grafting and the weight of the grafts and vesicular glands (male mice) were compared among groups by analysis of variance. In Experiment 1, mouse gonadal status (intact v. gonadectomized) did not affect the total graft weight (P > 0.05), but both the recipient mouse strain (nude v. SCID) and gender (male v. female) affected the total graft weight (2460 ± 320.9, 1420 ± 290.0, 758 ± 156.7, and 2780 ± 297.4, mean ± SEM, P < 0.0001 for SCID, nude, female, and male mice, respectively). In Experiment 2, the total graft weight was highest in the group of mice receiving 8 testis tissue fragments (192 ± 76.1, 695 ± 96.5, 2443 ± 338.8, and 1458 ± 305.4, mean ± SEM, P < 0.0001 for 2, 4, 8, or 16 fragment groups, respectively). These results collectively indicate that male SCID mice receiving 8 testis tissue fragments provide optimized conditions for the recovery of largest grafts. Research was supported by grants from the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Saskatchewan Health Research Foundation (SHRF) to A. Honaramooz and scholarships from the Western College of Veterinary Medicine and the International Peace Scholarship to S. Abbasi.

Effects of recipient mouse strain, sex and gonadal status on the outcome of testis tissue xenografting

2010 ◽  
Vol 22 (8) ◽  
pp. 1279 ◽  
Author(s):  
Sepideh Abbasi ◽  
Ali Honaramooz
Keyword(s):  
Severe Combined Immunodeficiency ◽  
Scid Mice ◽  
Seminiferous Tubules ◽  
Recipient Mouse ◽  
Immunodeficient Mice ◽  
Newborn Piglets ◽  
Female Nude ◽  
Different Strains ◽  
Gonadal Status ◽  
Testis Tissue

The aim of the present study was to examine factors that may affect the outcome of testis tissue xenografting. Recipient factors were examined by grafting small fragments of testis tissue from newborn piglets under the back skin of immunodeficient mice of different strains (severe combined immunodeficiency (SCID) v. nude), sex (male v. female) and gonadal status (intact v. gonadectomised) using a factorial design (eight groups; n = 7 mice per group). Recipient mice were killed after 8 months to compare the gross and histological attributes of the recovered grafts. Overall, approximately 94% of grafts were recovered. Gonadectomy of male or female recipients did not affect any of the measured outcomes of testis tissue xenografting, therefore data were pooled. Overall, in terms of sex, male mice and, in terms of strain, SCID mice tended to show higher gross and histological development of grafts. The group of female nude mice had the lowest graft recovery rate (75%) compared with the other groups (95–100%; P < 0.05). The grafts from male SCID mice were, on average the largest and had the highest percentage of spermatozoa-containing seminiferous tubules among all the groups (P < 0.05). These results suggest that male SCID mice provide a suitable recipient model for testis tissue xenografting and that the mice do not need to be castrated for optimal results.

scholarly journals Innate Resistance to Babesia Infection Is Influenced by Genetic Background and Gender

2001 ◽  
Vol 69 (12) ◽  
pp. 7955-7958 ◽  
Author(s):  
Irma Aguilar-Delfin ◽  
Mary J. Homer ◽  
Peter J. Wettstein ◽  
David H. Persing
Keyword(s):  
Innate Immunity ◽  
Adaptive Immunity ◽  
Genetic Background ◽  
Acquired Immunity ◽  
Male Mice ◽  
Innate And Adaptive Immunity ◽  
Innate Resistance ◽  
Immunodeficient Mice ◽  
C3h Mice ◽  
And Gender

ABSTRACT Infection of severe combined immunodeficient mice withBabesia sp. strain WA1 was studied to assess the contributions of innate and adaptive immunity in resistance to acute babesiosis. The scid mutation showed little effect in genetically susceptible C3H mice and did not decrease the inherent resistance of C57BL/6 mice to the infection, suggesting that innate immunity plays a central role in determining the course ofBabesia infection in these strains. In contrast, thescid mutation dramatically impaired resistance in moderately susceptible BALB/c mice, suggesting that acquired immunity may play an important secondary role. In comparison to their female counterparts, male mice of different genetic backgrounds showed increased resistance to the infection, indicating that the gender of the host may influence protection against babesiosis.

Extragonadal effects of luteinizing hormone in mice

1989 ◽  
Vol 121 (4) ◽  
pp. 587-594 ◽  
Author(s):  
Kaoru Nomura ◽  
David W. Puett ◽  
David Puett ◽  
Kazuo Shizume ◽  
Grant W. Liddle
Keyword(s):  
Physiological Role ◽  
Male Mice ◽  
Intact Female ◽  
Intact Male ◽  
Kidney Weight ◽  
Kidney Size ◽  
Female Mice ◽  
Cellular Hypertrophy ◽  
Kidney Growth

Abstract. LH is composed of isoforms which exhibit microheterogeneity. We recently demonstrated that a particular ovine or porcine LH preparation (G100-fr.3) stimulates kidney growth. This study was conducted to clarify the physiological role of this renotropic activity and other extragonadal effects of the ovine LH preparation in CD-1 mice. Hypophysectomy caused a significantly greater reduction in relative dry kidney weight (i.e. g/100 g body weight) when compared to adrenalectomy, castration, thyroidectomy, and castration plus thyroidectomy. Supplementation with G100-fr.3 in these animals partially restored not only kidney size but also DNA, RNA and protein content. Treatment with standard LH preparations (NIDDKoLH24 and G3-268DA), as well as PRL, GH, FSH and TSH, failed to reverse the renal atrophy induced by hypophysectomy and castration. Administration of testosterone to castrated hypophysectomized mice increased kidney weight and RNA content, but not renal DNA. The relative dry kidney weight increased significantly at the onset of puberty in intact male mice, but not in castrated males or intact female mice. In addition, human CG increased kidney size in hypophysectomized male mice, but not in castrated hypophysectomized animals. These findings indicate that LH isoforms may regulate kidney growth in the male mouse both directly as a renotropin stimulating hyperplasia and indirectly as a gonadotropin via testicular androgen, producing cellular hypertrophy. It was also noted that G100-fr.3 decreased hepatic weight, DNA, RNA and protein, but produced no significant change in the spleen, heart or adrenal glands in castrated-hypophysectomized mice. Such extragonadal effects of G100-fr.3 were also observed in intact female mice. These results suggest that certain LH isoforms may have extragonadal actions involving the kidney and liver.

Membrane estrogen receptor α is essential for estrogen signaling in the male skeleton

2018 ◽  
Vol 239 (3) ◽  
pp. 303-312 ◽  
Author(s):  
H H Farman ◽  
K L Gustafsson ◽  
P Henning ◽  
L Grahnemo ◽  
V Lionikaite ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptor Α ◽  
Estrogen Signaling ◽  
Areal Bone Mineral Density ◽  
Male Mice ◽  
Mineral Density ◽  
Intact Male ◽  
Trabecular Thickness ◽  
Total Body

The importance of estrogen receptor α (ERα) for the regulation of bone mass in males is well established. ERα mediates estrogenic effects both via nuclear and membrane-initiated ERα (mERα) signaling. The role of mERα signaling for the effects of estrogen on bone in male mice is unknown. To investigate the role of mERα signaling, we have used mice (Nuclear-Only-ER; NOER) with a point mutation (C451A), which results in inhibited trafficking of ERα to the plasma membrane. Gonadal-intact male NOER mice had a significantly decreased total body areal bone mineral density (aBMD) compared to WT littermates at 3, 6 and 9 months of age as measured by dual-energy X-ray absorptiometry (DEXA). High-resolution microcomputed tomography (µCT) analysis of tibia in 3-month-old males demonstrated a decrease in cortical and trabecular thickness in NOER mice compared to WT littermates. As expected, estradiol (E2) treatment of orchidectomized (ORX) WT mice increased total body aBMD, trabecular BV/TV and cortical thickness in tibia compared to placebo treatment. E2 treatment increased these skeletal parameters also in ORX NOER mice. However, the estrogenic responses were significantly decreased in ORX NOER mice compared with ORX WT mice. In conclusion, mERα is essential for normal estrogen signaling in both trabecular and cortical bone in male mice. Increased knowledge of estrogen signaling mechanisms in the regulation of the male skeleton may aid in the development of new treatment options for male osteoporosis.

scholarly journals Neural Determinants of Pulsatile Luteinizing Hormone Secretion in Male Mice

Endocrinology ◽  
2020 ◽  
Vol 161 (2) ◽  
Author(s):  
Su Young Han ◽  
Isaiah Cheong ◽  
Tim McLennan ◽  
Allan E Herbison
Keyword(s):  
Luteinizing Hormone ◽  
High Frequency ◽  
Pulse Generator ◽  
Hormone Secretion ◽  
Pulse Frequency ◽  
Male Mice ◽  
Intact Male ◽  
Luteinizing Hormone Secretion ◽  
Pulse Profile ◽  
Lh Secretion

Abstract The gonadotrophin-releasing hormone (GnRH) pulse generator drives pulsatile luteinizing hormone (LH) secretion essential for fertility. However, the constraints within which the pulse generator operates to drive efficient LH pulsatility remain unclear. We used optogenetic activation of the arcuate nucleus kisspeptin neurons, recently identified as the GnRH pulse generator, to assess the efficiency of different pulse generator frequencies in driving pulsatile LH secretion in intact freely behaving male mice. Activating the pulse generator at 45-minute intervals generated LH pulses similar to those observed in intact male mice while 9-minute interval stimulation generated LH profiles indistinguishable from gonadectomized (GDX) male mice. However, more frequent activation of the pulse generator resulted in disordered LH secretion. Optogenetic experiments directly activating the distal projections of the GnRH neuron gave the exact same results, indicating the pituitary to be the locus of the high frequency decoding. To evaluate the state-dependent behavior of the pulse generator, the effects of high-frequency activation of the arcuate kisspeptin neurons were compared in GDX and intact mice. The same stimulus resulted in an overall inhibition of LH release in GDX mice but stimulation in intact males. These studies demonstrate that the GnRH pulse generator is the primary determinant of LH pulse profile and that a nonlinear relationship exists between pulse generator frequency and LH pulse frequency. This may underlie the ability of stimulatory inputs to the pulse generator to have opposite effects on LH secretion in intact and GDX animals.

scholarly journals Urine from Sexually Mature Intact Male Mice Contributes to Increased Cardiovascular Responses during Free-Roaming and Restrained Conditions

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Dexter L. Lee ◽  
Justin L. Wilson
Keyword(s):  
Heart Rate ◽  
Mean Arterial Pressure ◽  
Male Mouse ◽  
Cardiovascular Responses ◽  
Mature Male ◽  
Physical Contact ◽  
Male Mice ◽  
Intact Male ◽  
Baseline Values ◽  
Sexually Mature

Pheromones in the urine regulate aggression of male mice and castrated males produce less of these pheromones. We tested the hypothesis that pheromones in the urine of sexually mature-intact (SMI) males placed in the cage bedding of an individually housed male mouse or in a mouse restrainer would contribute to a significant increase in mean arterial pressure (MAP), heart rate (HR), and activity. Sexually mature male C57BL/6 mice were implanted with a biotelemetry transmitter to measure MAP, HR, and activity. Urine (200 μL) from SMI mice placed in the cages of singularly housed male mice caused significant changes above baseline values for MAP (21±4 mmHg), HR (145±25 bpm), and activity (9±2 counts) when compared to urine from castrated mice-induced MAP (11±3 mmHg), HR (70±15 bpm), and activity (5±1 counts). Pretreatment with terazosin significantly reduced the change in MAP (9±3 mmHg), heart rate (90±15 bpm), and activity (4±2 counts) responses to urine from SMI males. Saline did not significantly increase MAP, HR, or activity in any group. During restraint, urine from SMI mice caused a significant change in MAP (5±0.4 mmHg) and HR (17±1 bpm); urine from castrated mice did not cause a significant increase in MAP and HR. Our results demonstrate that a significant increase in MAP, HR, and activity occurs when male mice are exposed to urine pheromones from SMI males. In summary, pheromones in the urine of SMI male excreted in the cage bedding and mouse restrainers contribute to a significant increase in cardiovascular responses in the absence of direct physical contact with a different male mouse or animal handler.

Regeneration of testis tissue after ectopic implantation of porcine testis cell aggregates in mice: improved consistency of outcomes and in situ monitoring

2020 ◽  
Vol 32 (6) ◽  
pp. 594 ◽  
Author(s):  
Awang Hazmi Awang-Junaidi ◽  
Jaswant Singh ◽  
Ali Honaramooz
Keyword(s):  
De Novo ◽  
Ultrasound Biomicroscopy ◽  
In Situ Monitoring ◽  
Cell Aggregates ◽  
Tissue Development ◽  
Immunodeficient Mice ◽  
Non Invasive ◽  
Old Donor ◽  
Testis Tissue

Ectopic implantation of donor testis cell aggregates in recipient mice results in de novo formation or regeneration of testis tissue and, as such, provides a unique invivo model for the study of testis development. However, currently the results are inconsistent and the efficiency of the model remains low. This study was designed to: (1) examine several factors that can potentially improve the consistency and efficiency of this model and (2) explore the use of ultrasound biomicroscopy (UBM) for the non-invasive invivo evaluation of implants. Testis cell aggregates, containing ~40% gonocytes, from 1-week-old donor piglets were implanted under the back skin of immunodeficient mice through skin incisions using gel matrices or through subcutaneous injection without using gel matrices. The addition of gel matrices led to inconsistent tissue development; gelatin had the greatest development, followed by collagen, whereas agarose resulted in poor development. The results also depended on the implanted cell numbers since implants with 100×106 cells were larger than those with 50×106 cells. The injection approach for cell implantation was less invasive and resulted in more consistent and efficient testis tissue development. UBM provided promising results as a means of non-invasive monitoring of implants.

scholarly journals 2-Methoxyestradiol Reduces Angiotensin II–Induced Hypertension and Renal Dysfunction in Ovariectomized Female and Intact Male Mice

Hypertension ◽  
2017 ◽  
Vol 69 (6) ◽  
pp. 1104-1112 ◽  
Author(s):  
Ajeeth K. Pingili ◽  
Karen N. Davidge ◽  
Shyamala Thirunavukkarasu ◽  
Nayaab S. Khan ◽  
Akemi Katsurada ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Renal Dysfunction ◽  
Male Mice ◽  
Intact Male ◽  
Induced Hypertension

Macrophages Prevent Human Red Blood Cell Reconstitution In NOD/SCID and NOD/SCID/γc−/− Mice.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3723-3723
Author(s):  
Zheng Hu ◽  
Yong-Guang Yang
Keyword(s):  
Mononuclear Cells ◽  
Conflicts Of Interest ◽  
Embryonic Stem ◽  
Humanized Mice ◽  
In Vivo Model ◽  
Recipient Mouse ◽  
Hematopoietic Stem ◽  
Immunodeficient Mice ◽  
Human Rbcs

Abstract Abstract 3723 An animal model supporting human erythropoiesis will be highly valuable for assessing the biological function of human RBCs under physiological and disease settings, and for evaluating protocols of in vitro RBC differentiation from human embryonic stem cells. Although immunodeficient mice on the NOD background have been widely used to study human hematopoietic stem cell function in vivo, the successful use of these mice in the study of human erythropoiesis and RBC function has not been reported. We have previously shown that co-transplantation of human fetal thymic tissue (under renal capsule) and CD34+ fetal liver cells (FLCs; i.v.) in NOD/SCID or NOD/SCID/γc−/− mice results in the development of multilineage human hematopoietic cells. Here, we analyzed human RBC reconstitution in these humanized mice. Although a large number of human erythrocytes, which consisted predominantly of immature nucleated erythrocytes, were detected in the bone marrow of human fetal thymus/CD34+ FLC-grafted mice, human RBCs were undetectable in blood of these mice, even in those with nearly full human chimerism in peripheral blood mononuclear cells (PBMCs). Recipient mouse macrophage-mediated rejection is, at least, one of the major mechanisms responsible for the lack of human RBCs in these mice, as human RBCs became detectable in blood following macrophage depletion and disappeared again after withdrawal of treatment. Furthermore, treatment with human erythropoietin (EPO) and human IL-3 significantly increased human RBC reconstitution in mice that were depleted of macrophages. Like the human RBCs developed in the humanized mice, exogenously injected normal human RBCs were also rapidly rejected by macrophages in NOD/SCID mice. Taken together, our data demonstrate that human RBCs are highly susceptible to rejection by macrophages in immunodeficient mice. Thus, strategies for preventing human RBC rejection by macrophages are required for using immunodeficient mice as an in vivo model to study human erythropoiesis and RBC function. Disclosures: No relevant conflicts of interest to declare.

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