scholarly journals 1 LONG TERM HEALTH AND BEHAVIOR OF ICSI PRODUCED MICE

2005 ◽  
Vol 17 (2) ◽  
pp. 151
Author(s):  
R. Fernandez-Gonzalez ◽  
P. Moreira ◽  
A. Bilbao ◽  
M.A. Ramirez ◽  
M. Perez-Crespo ◽  
...  

Intracytoplasmic sperm injection (ICSI) is a relatively new treatment for human male-related infertility (1992) and for the production of transgenic animals (1995). However, ICSI bypasses many natural biological processes such as sperm maturation, interaction within the female genital tract, sperm capacitation, interaction with oocyte vestments, and sperm membrane fusion with the oocyte. With the widespread use of this technology, its potential adverse outcomes need to be ascertained. It is theoretically possible that ICSI may cause specific problems through injury to the sperm or egg or injection of damaged or defective sperm. Here, we determined if ICSI has a long-term effect on mouse growth, behavior, and health. Female CD1 mice were superovulated and oocytes were injected with frozen-thawed spermatozoa (without cryoprotector or chelating agent) obtained from CD1 mice epididymes (Moreira et al. 2004 Biol. Reprod. 71, in press). Embryos were cultured 24 h in KSOM, and 2-cell embryos were transferred into CD1 females. Fifty-six mice (36 males and 20 females) produced by ICSI and 41 control mice (18 males and 23 females) obtained from in vivo-fertilized mice were analyzed. On week 20, animals were submitted to the following behavior tests: locomotor activity (open field), exploratory/anxiety behavior (elevated plus maze, open field), and spatial memory (free-choice exploration paradigm in Y maze). Comparison between groups was made using analysis of variance followed by least significant difference post hoc test. Postnatal weight gain of female mice produced by ICSI was heavier than for their control counterparts from 10 weeks on (P < 0.01). Males produced by ICSI showed more anxiety and lower locomotion in the p-maze and the Y-maze tests (P < 0.05), but no significant differences were found in the open-field test. Also, no differences were found in spatial memory or in the habituation pattern. Anatomopathological analysis of animals at 16 months of age showed some large organs (heart, lung, and liver; P < 0.01) and an increase in pathologies (15% of animals produced by ICSI presented some solid tumors in lung, dermis of back, or neck). Loss of imprinting is one of the most common epigenetic changes associated with the development of a wide variety of tumours. An association between some imprinting disorders, rare tumors, and ICSI has recently been reported in humans (Wittermer et al. 2004 Med. Sci. 20, 352). We are now analyzing the epigenetic modifications that may be induced by our ICSI protocol and whether the sperm DNA fragmentation that may take place during sperm freezing before the ICSI procedure might not only affect postnatal development, growth, and physiology, but also increase the risk of tumors in adult animals. Our data suggest that our ICSI method produces mice with sex-dimorphic alterations in aberrant growth and anxiety, as well as with a higher probability of developing a solid tumor.

2013 ◽  
Vol 2013 ◽  
pp. 1-5
Author(s):  
Olakunle James Onaolapo ◽  
Adejoke Yetunde Onaolapo

This study set out to assess the neurobehavioral effects of subchronic, oral bromocriptine methanesulfonate using the open field and the Y-maze in healthy male mice. Sixty adult Swiss albino mice were assigned into three groups. Controls received normal saline, while test groups received bromocriptine methanesulfonate at 2.5 and 5 mg/kg/day, respectively, for a period of 21 days. Neurobehavioral tests were carried out on days 1 and 21 after administration. Open field assessment on day 1 after administration revealed significant increase in grooming at 2.5 and 5 mg/kg, while horizontal and vertical locomotion showed no significant changes. Day 1 also showed no significant changes in Y-maze alternation. On day 21, horizontal locomotion, rearing, and grooming were increased significantly at 2.5 and 5 mg/kg doses after administration; also, spatial memory was significantly enhanced at 2.5 mg/kg. In conclusion, the study demonstrates the ability of oral bromocriptine to affect neurobehavior in normal mice. It also suggests that there is a cumulative effect of oral bromocriptine on the behaviors studied with more changes being seen after subchronic administration rather than after a single oral dose.


1997 ◽  
Vol 31 (3) ◽  
pp. 264-270 ◽  
Author(s):  
M. Santos ◽  
K. J. H. Wienk ◽  
M. W. Schilham ◽  
H. Clevers ◽  
M. de Sousa ◽  
...  

An improved and sensitive method for studying iron absorption in mice with alterations in body iron stores is described. Mice with varying iron status were given a double isotope-labelled test dose containing 59Fe and 51Cr as a non-absorbable indicator, via an oroesophageal needle. Using a whole-body counter it was possible to measure in vivo the initial mucosal iron uptake and long-term iron retention and to calculate mucosal iron transfer. A significant difference was demonstrated between normal and both anaemic and dietary iron-loaded mice with regard to the various steps of iron absorption. When mice were tested twice for iron absorption, the results were highly reproducible. In conjunction with other parameters, the method described is useful in studying the mechanism and the regulation of iron absorption in mice.


2016 ◽  
Vol 60 (7) ◽  
pp. 4005-4012 ◽  
Author(s):  
Ju Young Lee ◽  
Hyun Jung Lee ◽  
Yong Kyun Kim ◽  
Shinae Yu ◽  
Jiwon Jung ◽  
...  

ABSTRACTThere have been concerns about an association of fluoroquinolone (FQ) use prior to tuberculosis (TB) diagnosis with adverse outcomes. However, FQ use might prevent clinical deterioration in missed TB patients, especially in those who are immunocompromised, until they receive definitive anti-TB treatment. All adult immunocompromised patients with smear-negative and culture-positive TB at a tertiary care hospital in Korea over a 2-year period were included in this study. Long-term FQ (≥7 days) use was defined as exposure to FQ for at least 7 days prior to TB diagnosis. A total of 194 patients were identified: 33 (17%) in the long-term FQ group and 161 (83%) in the comparator, including a short-term FQ group (n= 23), non-FQ group (n= 78), and a group receiving no antibiotics (n= 60). Patients in the long-term FQ group presented with atypical chest radiologic pattern more frequently than those in the comparator (77% [24/31] versus 46% [63/138];P= 0.001). The median time from mycobacterial test to positive mycobacterial culture appeared to be longer in the long-term FQ group (8.1 weeks versus 7.7 weeks;P= 0.09), although the difference was not statistically significant. Patients in the long-term FQ group were less likely to receive empirical anti-TB treatment (55% versus 74%;P= 0.03). The median time from mycobacterial test to anti-TB therapy was longer in the long-term FQ group (4.6 weeks versus 2.2 weeks;P< 0.001), but there was no significant difference in FQ resistance (0% versus 3%;P> 0.99) or in the 30-day (6% versus 6%;P> 0.99) or 90-day (12% versus 12%;P> 0.99) mortality rate between the two groups. FQ exposure (≥7 days) prior to TB diagnosis in immunocompromised patients appears not to be associated with adverse outcomes.


2020 ◽  
Vol 13 (10) ◽  
pp. 318
Author(s):  
Rahim Ullah ◽  
Gowhar Ali ◽  
Nisar Ahmad ◽  
Muhammad Akram ◽  
Geeta Kumari ◽  
...  

Alzheimer’s disease (AD) is an irreversible and chronic neurological disorder that gradually destroys memory and thinking skills. The research study was designed to investigate the underlying molecular signaling involved in the neuroprotective effects of cyclopentanone derivative i.e., 2-(hydroxyl-(3-nitrophenyl)methyl)cyclopentanone (3NCP) as a therapeutic agent for AD. In this study, In vivo studies were carried out on a well-known 5xFAD mice model using different behavioural test models such as open field, rotarod, Morris water maze (MWM), and Y-maze tests. Furthermore, in vitro cholinesterase inhibition activity assays were carried out. The frontal cortex (FC) and hippocampus (HC) homogenates were tested for the levels/activities of cholinesterases, glutathione (GSH), glutathione S-transferase (GST), and catalase. Furthermore, the hippocampal expression of inflammatory cytokines was observed via RT-PCR and western blot. The results of in vivo studies show an enhancement in the learning behavior. The 3NCP treatment reduced latency time in MWM and Y-maze tests, also increase spontaneous alternation indicate significant effect of 3NCP on memory. Furthermore, open field and rotarod studies revealed that 3NCP does not cause motor coordination deficit. The results of the in vitro studies revealed that the IC50 values of the 3NCP against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were 16.17 and 20.51 µg/mL, respectively. This decline in AChE and BChE was further supported by ex vivo studies. Further, the 3NCP mitigates the GSH level, GST, and catalase activities in HC and FC. The mRNA and protein expression of inflammatory cytokines (IL-1β, IL-6, TNF-α) markedly declined in RT-PCR and western blotting. The results of the current study conclusively demonstrate that 3NCP reduces oxidative stress and mitigates neuroinflammation in 5xFAD mice, implying that 3NCP may be a potential therapeutic candidate for AD treatment in the future.


2020 ◽  
Vol 1 (10) ◽  
pp. 653-662
Author(s):  
Luthfur Rahman ◽  
Mazin S. Ibrahim ◽  
Lyndsay Somerville ◽  
Matthew G. Teeter ◽  
Douglas D. Naudie ◽  
...  

Aims To compare the in vivo long-term fixation achieved by two acetabular components with different porous ingrowth surfaces using radiostereometric analysis (RSA). Methods This was a minimum ten-year follow-up of a prospective randomized trial of 62 hips with two different porous ingrowth acetabular components. RSA exams had previously been acquired through two years of follow-up. Patients returned for RSA examination at a minimum of ten years. In addition, radiological appearance of these acetabular components was analyzed, and patient-reported outcome measures (PROMs) obtained. Results In all, 15 hips were available at ten years. There was no statistically significant difference in PROMS between the two groups; PROMs were improved at ten years compared to preoperative scores. Conventional radiological assessment revealed well-fixed components. There was minimal movement for both porous surfaces in translation (X, Y, Z, 3D translation in mm (median and interquartile range (IQR)), StikTite (Smith and Nephew, Memphis, Tennessee, USA): 0.03 (1.08), 0.12 (0.7), 0.003 (2.3), 0.37 (0.30), and Roughcoat (Smith and Nephew): -0.6 (0.59),–0.1 (0.49), 0.1 (1.12), 0.48 (0.38)), and rotation (X, Y, Z rotation in degrees (median and IQR), (Stiktite: -0.4 (3), 0.28 (2), -0.2 (1), and Roughcoat: - 0.4 (1),–0.1 (1), 0.2 (2)). There was no statistically significant difference between the two cohorts (p-value for X, Y, Z, 3D translation - 0.54, 0.46, 0.87, 0.55 and for X, Y, Z rotation - 0.41, 0.23, 0.23 respectively) at ten years. There was significant correlation between two years and ten years 3D translation for all components ( r = 0.81(p =< 0.001)). Conclusion Both porous ingrowth surfaces demonstrated excellent fixation on plain radiographs and with RSA at ten years. Short-term RSA data are good predictors for long-term migration data.


2021 ◽  
Vol 12 ◽  
Author(s):  
Thanh Tin Nguyen ◽  
Gi-Sung Nam ◽  
Jin-Ju Kang ◽  
Gyu Cheol Han ◽  
Ji-Soo Kim ◽  
...  

Objectives: To investigate the deficits of spatial memory and navigation from unilateral vestibular deafferentation (UVD) and to determine the efficacy of galvanic vestibular stimulation (GVS) for recovery from these deficits using a mouse model of unilateral labyrinthectomy (UL).Methods: Thirty-six male C57BL/6 mice were allocated into three groups that comprise a control group and two experimental groups, UVD with (GVS group) and without GVS intervention (non-GVS group). In the experimental groups, we assessed the locomotor and cognitive behavioral function before (baseline) and 3, 7, and 14 days after surgical UL, using the open field (OF), Y maze, and Morris water maze (MWM) tests. In the GVS group, the stimulations were applied for 30 min daily from postoperative day (POD) 0–4 via the electrodes inserted subcutaneously close to both bony labyrinths.Results: Locomotion and spatial cognition were significantly impaired in the mice with UVD non-GVS group compared to the control group. GVS significantly accelerated recovery of locomotion compared to the control and non-GVS groups on PODs 3 (p &lt; 0.001) and 7 (p &lt; 0.05, Kruskal–Wallis and Mann–Whitney U tests) in the OF and Y maze tests. The mice in the GVS group were better in spatial working memory assessed with spontaneous alternation performance and spatial reference memory assessed with place recognition during the Y maze test than those in the non-GVS group on POD 3 (p &lt; 0.001). In addition, the recovery of long-term spatial navigation deficits during the MWM, as indicated by the escape latency and the probe trial, was significantly better in the GVS group than in the non-GVS group 2 weeks after UVD (p &lt; 0.01).Conclusions: UVD impairs spatial memory, navigation, and motor coordination. GVS accelerated recoveries in short- and long-term spatial memory and navigation, as well as locomotor function in mice with UVD, and may be applied to the patients with acute unilateral vestibular failure.


Zygote ◽  
1997 ◽  
Vol 5 (3) ◽  
pp. 273-276 ◽  
Author(s):  
Catherine Guyader-Joly ◽  
Chaqué Khatchadourian ◽  
Yves Ménézo

SummaryAs glycine is one of the most concentrated amino acids in the female genital tract, we investigated its uptake by bovine in vitro matured/in vitro fertilised blastocysts in the presence of increasing concentrations of radiolabelled glycine. We also determined methionine uptake by in vitro and in vivo produced embryos. In our study, the hypothesis of more than one site of enzyme activity for glycine substrate was not validated. We determined a Vmax of 23.4fmol/min per embryo and a Km value of 13.3μM. No significant difference was observed either between in vivo and in vitro derived embryos or between grade 1 and grade 2 embryos for methionine uptake. The methionine and glycine uptake of a day 7 bovine was similar to that of a day 4 mouse blastocyst. This is rather low if we consider the relative cell numbers.


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