scholarly journals Cryopreserved ovarian tissues can maintain a long-term function after heterotopic autotransplantation in rat

Reproduction ◽  
2009 ◽  
Vol 138 (3) ◽  
pp. 519-525 ◽  
Author(s):  
Xiaohui Deng ◽  
Hua Zheng ◽  
Xuan Yu ◽  
Hongling Yu ◽  
Chengmei Zhang ◽  
...  

The functional longevity of cryopreserved ovarian grafts is one of the most challenging questions regarding ovarian transplantation at present. This study used a rat ovarian grafting model to investigate whether ovarian tissues from adult rats, which had been cryopreserved by vitrification and followed by heterotopic transplantation, could establish long-term hormone secretion and follicle development. Fresh and cryopreserved ovarian tissues were autologously transplanted under the kidney capsule. One-third of the animals in each group (sham-operated, fresh autografts, cryopreserved autografts, or castrated) were killed 5, 8, or 10 months after transplantation. Vaginal cytology, serum estradiol (E2), progesterone, and the morphology of the reproductive tract were used to assess ovarian function. Both fresh and cryopreserved ovarian grafts survived well in all the animal models with comparable proportion of follicles at each stage of folliculogenesis at all three time points. The serum E2 and progesterone concentrations in the groups with fresh or cryopreserved grafts remained comparable with those in sham-operated controls at all investigated time points. However, a loss of grafts and primordial follicles following heterotopic transplantation was noted. In conclusion, the heterotopic autotransplantation of vitrified ovarian tissues from adult rat without vascular anastomosis can maintain long-term ovarian function and exert endocrine function in target organs, in spite of the reduction in follicle pool.

1995 ◽  
Vol 74 (4) ◽  
pp. 1793-1799 ◽  
Author(s):  
M. L. Errington ◽  
T. V. Bliss ◽  
G. Richter-Levin ◽  
K. Yenk ◽  
V. Doyere ◽  
...  

1. We examined the efficacy of low-frequency trains (1-5 Hz) in producing long-term depression (LTD) or depotentiation in the hippocampus of the awake adult rat and in anesthetized rats aged from 10 days to 3 mo. 2. In the dentate gyrus we found no evidence that low-frequency trains produce either depotentiation or LTD in the awake, adult animal or in the anesthetized animal at any age tested (10 days-adult). 3. In area CA1 of both awake and anesthetized adult rats, we also found no evidence that low-frequency trains induced either LTD or depotentiation. Only in area CA1 of very young rats (10-11 days) was clear evidence for LTD and depotentiation obtained; at this age experiments were only possible in anesthetized animals. By 16 days, the ability to display both LTD and depotentiation was lost. 4. These experiments suggest that repetitive low-frequency stimulation evokes a developmentally regulated form of activity-dependent depression that in the hippocampus is limited to specific pathways in the young animal. Our results leave open the question of whether alternative patterns of activity can induce LTD and/or depotentiation in the adult awake rat.


2021 ◽  
Author(s):  
Sara Y. Brucker ◽  
Thomas Hentrich ◽  
Julia M. Schulze-Hentrich ◽  
Martin Pietzsch ◽  
Noel Wajngarten ◽  
...  

The uterus is responsible for the nourishment and mechanical protection of the developing embryo and fetus and is an essential part in mammalian reproduction. The Mayer-Rokitansky-Kuester-Hauser (MRKH) syndrome is characterized by agenesis of the uterus and upper part of the vagina in females with normal ovarian function. Although heavily studied, the cause of the disease is still enigmatic. Current research in the field of MRKH mainly focusses on DNA-sequencing efforts and, so far, failed to decipher the nature and heterogeneity of the disease, thereby holding back scientific and clinical progress. Here, we developed long-term expandable organoid cultures from endometrium found in uterine rudiment horns of MRKH patients. Phenotypically, they share great similarity with healthy control organoids and are surprisingly fully hormone responsive. Transcriptome analyses, however, identified an array of dysregulated genes that point at potentially disease-causing pathways altered during the development of the female reproductive tract. We consider the endometrial organoid cultures to be a powerful research tool that promise to enable an array of studies into the pathogenic origins of MRKH syndrome and possible treatment opportunities to improve patient quality of life.


1960 ◽  
Vol 199 (4) ◽  
pp. 701-706 ◽  
Author(s):  
Savino A. D'Angelo

Persistent vaginal estrus with uterine and pituitary hypertrophy were found in adult female rats 4–10 months after placement of preoptic and anterior hypothalamic lesions. Serum TSH, I131 release rate and histology of the thyroid and ascorbic acid concentration of adenohypophysis, ovary and adrenal were normal. Exposure of lesioned rats to cold (5°C, 36–55 days) profoundly altered pituitary-target gland functions. Ovarian atrophy and uterine involution resulted; vaginal cornification ceased. Pituitary hypertrophy was inhibited but ascorbic acid concentration was maintained. Serum and pituitary TSH levels decreased and acceleration of thyroidal radioiodine release was prevented. Apparent dichotomy in adrenal responses developed. Despite enlarged adrenals, plasma corticosterone level in cold stressed, operated rats averaged less than one-third that of intact controls. Adrenal ascorbic acid concentration remained normal. The results underscore the basic role of central nervous mechanisms in endocrine function under chronic cold stress. Hypothalamic lesions which permit adequate trophic hormone secretion at normal temperatures drastically curtail thyroidal and ovarian function and selectively limit adrenal responses in the cold.


2008 ◽  
Vol 104 (5) ◽  
pp. 1287-1294 ◽  
Author(s):  
Anita Pawar ◽  
Ying-Jie Peng ◽  
Frank J. Jacono ◽  
Nanduri R. Prabhakar

Previous studies suggest that carotid body responses to long-term changes in environmental oxygen differ between neonates and adults. In the present study we tested the hypothesis that the effects of chronic intermittent hypoxia (CIH) on the carotid body differ between neonates and adult rats. Experiments were performed on neonatal (1–10 days) and adult (6–8 wk) males exposed either to CIH (9 episodes/h; 8 h/day) or to normoxia. Sensory activity was recorded from ex vivo carotid bodies. CIH augmented the hypoxic sensory response (HSR) in both groups. The magnitude of CIH-evoked hypoxic sensitization was significantly greater in neonates than in adults. Seventy-two episodes of CIH were sufficient to evoke hypoxic sensitization in neonates, whereas as many as 720 CIH episodes were required in adults, suggesting that neonatal carotid bodies are more sensitive to CIH than adult carotid bodies. CIH-induced hypoxic sensitization was reversed in adult rats after reexposure to 10 days of normoxia, whereas the effects of neonatal CIH persisted into adult life (2 mo). Acute intermittent hypoxia (IH) evoked sensory long-term facilitation of the carotid body activity (sensory LTF, i.e., increased baseline neural activity following acute IH) in CIH-exposed adults but not in neonates. The effects of CIH were associated with hyperplasia of glomus cells in neonatal but not in adult carotid bodies. These observations demonstrate that responses to CIH differ between neonates and adults with regard to the magnitude of sensitization of HSR, susceptibility to CIH, induction of sensory LTF, reversibility of the responses, and morphological remodeling of the chemoreceptor tissue.


Author(s):  
Chu-Chun Huang ◽  
Chia-Hung Chou ◽  
Yu-Shih Yang ◽  
Hong-Nerng Ho ◽  
Chia-Tung Shun ◽  
...  

Abstract Cyclophosphamide (CP) could cause severe gonadotoxicity via imbalanced activation of primordial follicles through PI3K/AKT/mTOR activation. Whether metformin, a widely prescribed anti-diabetes agent with mTOR inhibitory effect, could preserve ovarian function against CP toxicity is unknown. Female C57BL/6 mice were randomized into seven groups (n = 11), including control, CP-alone, CP+metformin, CP+sirolimus or everolimus, metformin-alone and sirolimus-alone groups. The duration of pharmaceutical treatment was four weeks. CP treatment significantly impaired ovarian function and fertility in mice. CP+metformin treatment significantly attenuated the gonadotoxicity comparing to CP-alone treatment (Primordial follicle count: 17.6 ± 4.2 versus 10.3 ± 2.7 follicles/high-power field; p = 0.027). CP+metformin treatment also tended to increase antral follicular count (5.4 ± 1.1 versus 2.5 ± 1.6 follicles/section), serum AMH levels (4.6 ± 1.2 versus 2.0 ± 0.8 ng/ml) and the litter size (4.2 ± 1.3 versus 1.5 ± 1.0 mice per pregnancy), compared with CP-alone group. Expression of phospho-mTOR and the number of TUNEL-positive granulosa cells increased after CP treatment and decreased in the CP+metformin groups, suggesting the mTOR inhibitory and anti-apoptotic effects of metformin. In in vitro granulosa cell experiments, the anti-apoptotic effect of metformin was blocked after inhibiting p53 or p21 function, and the expression of p53 mRNA was blocked with AMPK inhibitor, suggesting that the anti-apoptotic effect was AMPK/p53/p21-mediated. In conclusion, concurrent metformin treatment during CP therapy could significantly preserve ovarian function and fertility and could be a promising novel fertility preserving agent during chemotherapy. The relatively acceptable cost and well-established long-term safety profiles of this old drug might prompt its further clinical application at a faster pace.


Endocrinology ◽  
2013 ◽  
Vol 154 (1) ◽  
pp. 400-409 ◽  
Author(s):  
Kazuki Hattori ◽  
Nobuyuki Shirasawa ◽  
Hikaru Suzuki ◽  
Takanobu Otsuka ◽  
Ikuo Wada ◽  
...  

In the transitional zone of the rat anterior pituitary, spontaneous and LHRH-induced Ca2+ dynamics were visualized using fluo-4 fluorescence Ca2+ imaging. A majority of cells exhibited spontaneous Ca2+ transients, while small populations of cells remained quiescent. Approximately 70% of spontaneously active cells generated fast, oscillatory Ca2+ transients that were inhibited by cyclopiazonic acid (10 μm) but not nicardipine (1 μm), suggesting that Ca2+ handling by endoplasmic reticulum, but not Ca2+ influx through voltage-dependent L-type Ca2+ channels, plays a fundamental role in their generation. In the adult rat anterior pituitary, LHRH (100 μg/ml) caused a transient increase in the Ca2+ level in a majority of preparations taken from the morning group rats killed between 0930 h and 1030 h. However, the second application of LHRH invariably failed to elevate Ca2+ levels, suggesting that the long-lasting refractoriness to LHRH stimulation was developed upon the first challenge of LHRH. In contrast, LHRH had no effect in most preparations taken from the afternoon group rats euthanized between 1200 h and 1400 h. In the neonatal rat anterior pituitary, LHRH caused a suppression of spontaneous Ca2+ transients. Strikingly, the second application of LHRH was capable of reproducing the suppression of Ca2+ signals, indicating that the refractoriness to LHRH had not been established in neonatal rats. These results suggest that responsiveness to LHRH has a long-term refractoriness in adult rats, and that the physiological LHRH surge may be clocked in the morning. Moreover, LHRH-induced excitation and associated refractoriness appear to be incomplete in neonatal rats and may be acquired during development.


2018 ◽  
Vol 3 (1) ◽  

Radioactive iodines emitted following nuclear accidents are responsible for the dramatic increase of the late-onset thyroid cancer. Until the Fukushima disaster, a single dose of potassium iodide (KI) has been considered as an efficient countermeasure. Indeed, recently it has been suggested that repeated administration of KI may be necessary to ensure adequate protection in case of protracted exposure. Whereas, the effect of a single dose of KI has largely been studied ensuring its safety, studies regarding adverse effects of repeated iodine thyroid blocking (ITB) administration are scarce. Our objective was to assess the long term overall impact of KI in adult rats after repeated intake. Adult Wistar rats were subjected to either KI or saline solution over eight days. Biochemical homeostasis, hormones level, autoimmunity status, thyroid morphology and thyroid transcriptome profile were analyzed thirty days after the discontinuation of KI administration. Biochemical parameters, plasma levels of TSH; thyroid hormones; anti-TPO and anti-Tg did not differ between treated and control rats, the thyroid histology was not affected by the treatment and no long term transcriptome signature attributable to the treatment was noticed. Based on these data, we conclude the safety of repeated KI intake in adult rats; these data are prominent and may contribute to the ongoing development of KI guidelines and marketing authorization.


1971 ◽  
Vol 51 (4) ◽  
pp. 665-674 ◽  
Author(s):  
E. B. CRAMER ◽  
R. E. TRAUM ◽  
S. A. D'ANGELO

SUMMARY Pituitary and serum follicle-stimulating hormone (FSH) concentrations were determined by the Steelman—Pohley ovarian augmentation bioassay method in normal adult rats and in rats subjected to ovariectomy and/or electrolytic lesioning of the tuberal hypothalamus 10, 30 or 90 days previously. Ovariectomy resulted in a rapid, significant increase in FSH concentration of the adenohypophysis. Pituitary FSH concentrations were increased sixfold 10 and 30 days after ovariectomy and by 90 days were increased by 700%. (Hormone stores in the adenohypophysis increased correspondingly.) Serum FSH levels in ovariectomized rats also increased but at a slower rate. Ten days after ovariectomy, serum FSH levels were still normal. Thirty and ninety days postoperatively, serum FSH titres were doubled and quintupled, respectively. Chronic median eminence lesions eventually caused obesity, a marked atrophy of the reproductive system and significant increase in the FSH concentration of the adenohypophysis. Follicle-stimulating hormone was not detected in the sera of rats with short-term lesions but serum hormone levels were in the normal range 30 and 90 days after the lesions were made. Complete destruction of the median eminence in ovariectomized rats was associated with further increase in pituitary FSH concentration and content. Ninety days after simultaneous lesioning and ovariectomy, FSH concentration of the adenohypophysis was almost twice that of the ovariectomized control and the hormone content was about 14 times that in the normal pituitary. In contrast, the raised FSH serum levels observed after long-term ovariectomy were significantly reduced (50%). It is concluded that chronic median eminence lesions which induce obesity and ovarian atrophy in rats differentially affect synthesis and release of FSH by the adenohypophysis.


1996 ◽  
Vol 134 (5) ◽  
pp. 655-659 ◽  
Author(s):  
Sompongse Suwanwalaikorn ◽  
Boonsong Ongphiphadhanakul ◽  
Lewis E Braverman ◽  
Daniel T Baran

Suwanwalaikorn S, Ongphiphadhanakul B, Braverman LE, Baran DT. Differential responses of femoral and vertebral bones to long-term excessive l-thyroxine administration in adult rats. Eur J Endocrinol 1996;134:655–9. ISSN 0804–4643 Recent studies suggest that thyroid-stimulating hormone suppressive doses of thyroid hormone decrease bone mass in humans and growing rats. To determine the long-term effects of excessive l-thyroxine administration on the femur and vertebrae in an adult rat model, 20 male Sprague-Dawley rats (20 weeks old) were randomized into two groups. Group 1 received l-thyroxine (20 μg/100 g body weight ip daily), and group 2 received normal saline ip daily for 20 weeks. Femoral and lumbar vertebral bone mineral density measurements were performed at 0, 6, 15, 18 and 20 weeks of treatment. After 20 weeks of treatment, total RNA was isolated from both femoral and lumbar bones. Northern hybridization was performed with 32P-labeled DNA probes for osteocalcin, osteopontin, alkaline phosphatase and tartrate-resistant acid phosphatase. Significant decreases in bone mineral density in the femur of l-thyroxine-treated rats were observed after 15 weeks (p < 0.03). Lumbar bone mineral density was not affected. Both osteoblast (osteocalcin, osteopontin, alkaline phosphatase) and osteoclast (tartrate-resistant acid phosphatase) gene expression markers were increased significantly in the femoral bone (p < 0.001), but not in the lumbar vertebrae of the l-thyroxine-treated rats. We conclude that long-term administration of excessive doses of l-thyroxine to the adult rat preferentially affects femoral but not vertebral bone. This is manifested by decreased bone mineral density as well as increased gene expression markers for osteoblast and osteoclast activity in the femur. Daniel T Baran, Department of Orthopedics, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA


2006 ◽  
Vol 95 (6) ◽  
pp. 3519-3527 ◽  
Author(s):  
Jianqun Wu ◽  
Michael J. Rowan ◽  
Roger Anwyl

The induction of NMDA-receptor–dependent long-term potentiation (LTP) in adult CA1 is contingent on activation of Ca/calmodulin-dependent protein kinase II (CaMKII). However, little is known about kinase mediation of LTP in the dentate gyrus. In the present study, the involvement of the kinases CaMKII, PKA, and MAPK in the induction of LTP was studied in the dentate gyrus of adult rats. Individual application of selective inhibitors of CaMKII, MEK, or PKA did not inhibit induction of LTP. In contrast, coapplication of a CaMKII inhibitor with either a PKA or MEK inhibitor resulted in a strong block of LTP. Induction of LTP was blocked by the coapplication of the inhibitors CaMKII and PKA or MEK, both when they were applied 1 h before the induction stimulus and also when they were applied after the induction stimulus. Thus LTP is mediated by either of two parallel cascades, one involving CaMKII and the other PKA or MAPK. Moreover, these cascades are active for a certain period after the induction stimulus.


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