Paternal exposure to bupropion affects postnatal development in the offspring

2019 ◽  
Vol 31 (10) ◽  
pp. 1539
Author(s):  
E. S. A. M. Sanches ◽  
F. Tsuzuki ◽  
F. Joinhas ◽  
G. B. Figueiras ◽  
E. G. Moreira ◽  
...  

The aim of this study was to evaluate whether paternal exposure to bupropion hydrochloride (BUP), an inhibitor of dopamine and noradrenaline reuptake, would affect the postnatal development of offspring. Male mice were divided into a BUP-treated (40mgkg−1day−1 by gavage, 45 days) or control (saline by gavage, 45 days) group (n=20 in each group). From Day 35 to Day 45 of treatment, males were allowed to mate with drug-naïve female mice. Postnatal development of the offspring (both sexes) was evaluated from Postnatal day (PND) 1 to PND60. Physical development parameters (weight gain, body length, incisor eruption, pinna detachment), anogenital distance, vaginal opening, reflexes (palmar grasp, surface righting, negative geotaxis and adult gait) and some behavioural parameters (locomotor activity and anxiety-like behaviour) were altered in the offspring of BUP-treated males. The results demonstrate that paternal exposure to BUP induces long-lasting changes in the postnatal development of the offspring.

2017 ◽  
Vol 39 (2) ◽  
pp. 133
Author(s):  
Lucimara Aparecida Sensiate ◽  
Ana Clara Cerato Bispo ◽  
Karla Lorena Guarido ◽  
Joelle Toni-Ann Venice Freckleton ◽  
Maria José Salles

 Literature shows that surgical procedure could be necessary at any stage of pregnancy and can cause adverse effects on the mother and fetus. One of the most used anesthetics in surgical centers is propofol however; the safety during pregnancy has not been completely established. The objective of this study was to investigate the possible toxic and teratogenic effects on the intrauterine and post-natal development of mice exposed to the dose of 15 mg kg-1 propofol on the caudal vein fifth, tenth and fifteenth day of gestation. A significant reduction in weight gain was observed in female mice who received a 15 mg kg-1 dose of propofol on the fifth gestational day. A higher rate of embryonic loss post implantation and resorption was also observed in this group. In regards to physical development, the anesthetic increased significantly the offspring weight gain, the time in which pinna detachment occurred, and the anogenital distance of pups whose females received propofol on the fifteenth day of gestation. Based on these results, we concluded that administration of propofol in the beginning stages of gestation increases the number of abortions and promotes alterations in the physical development of pups whose mothers were anesthetized in the final stages of gestation. 


2000 ◽  
Vol 43 (4) ◽  
pp. 363-374
Author(s):  
M. Schmidt ◽  
T. Król ◽  
U. Renne ◽  
L. Panicke

Abstract. Title of the paper: Lysosomal proteolytic activity in the liver of growing mice The behaviour of the activity of some lysosomal proteolytic enzymes in Üie liver of mice, both selected and unselected for high body growth, was followed during the postnatal development. The activity of cathepsin D and L, the alanylaminopeptidase, the arginylaminopeptidase, the α-glucosidase and the N-acetyl-glucosaminidase was estimated in male mice aging 21, 28, 35 and 42 days. In the liver of animals with high body gain statistic significant lower activities (30–50 %) of all estimated enzymes were found, in comparison to the control mice. These results confirm the Statement mat inhibition of proteolysis is an immediate mechanism in the induction of growth.


2020 ◽  
Author(s):  
E. Matthew Morris ◽  
Roberto D. Noland ◽  
Michael E. Ponte ◽  
Michelle L. Montonye ◽  
Julie A. Christianson ◽  
...  

AbstractCentral integration of peripheral neural signals is one mechanism by which systemic energy homeostasis is regulated. Previous work described increased acute food intake following chemical reduction of hepatic fatty acid oxidation and ATP levels, which was prevented by common hepatic branch vagotomy (HBV). However, possible offsite actions of the chemical compounds confound the precise role of liver energy metabolism. Herein, we used a liver-specific PGC1a heterozygous (LPGC1a) mouse model, with associated reductions in mitochondrial fatty acid oxidation and respiratory capacity, to assess the role of liver energy metabolism in systemic energy homeostasis. LPGC1a male mice have 70% greater high-fat/high-sucrose (HFHS) diet-induced weight gain and 35% greater positive energy balance compared to wildtype (WT) (p<0.05). The greater energy balance was associated with altered feeding behavior and lower activity energy expenditure during HFHS in LPGC1a males. Importantly, no differences in HFHS-induced weight gain or energy metabolism was observed between female WT and LPGC1a mice. WT and LPGC1a mice underwent sham or HBV to assess whether vagal signaling was involved in HFHS-induced weight gain of male LPGC1a mice. HBV increased HFHS-induced weight gain (85%, p<0.05) in male WT, but not LPGC1a mice. As above, sham LPGC1a males gain 70% more weight during short-term HFHS feeding than sham WT (p<0.05). These data demonstrate a sexspecific role of reduced liver energy metabolism in acute diet-induced weight gain, and the need of more nuanced assessment of the role of vagal signaling in short-term diet-induced weight gain.Key Points SummaryReduced liver PGC1a expression results in reduced mitochondrial fatty acid oxidation and respiratory capacity in male mice.Male mice with reduced liver PGC1a expression (LPGC1a) demonstrate greater short-term high-fat/high-sucrose diet-induced weight gain compared to wildtype.Greater positive energy balance during HFHS feeding in male LPGC1a mice is associated with altered food intake patterns and reduced activity energy expenditure.Female LPGC1a mice do not have differences in short-term HFHS-induced body weight gain or energy metabolism compared to wildtype.Disruption of vagal signaling through common hepatic branch vagotomy increases short-term HFHS-induced weight gain in male wildtype mice, but does not alter male LPGC1a weight gain.


Diabetes ◽  
2020 ◽  
Vol 69 (6) ◽  
pp. 1110-1125 ◽  
Author(s):  
Bernd Coester ◽  
Christina Koester-Hegmann ◽  
Thomas A. Lutz ◽  
Christelle Le Foll

2020 ◽  
Vol 35 (8) ◽  
pp. 1740-1752 ◽  
Author(s):  
Md Saidur Rahman ◽  
Won-Ki Pang ◽  
Do-Yeal Ryu ◽  
Yoo-Jin Park ◽  
Myung-Geol Pang

Abstract STUDY QUESTION How does paternal exposure to bisphenol A (BPA) affect the fertility of male offspring in mice in future generations? SUMMARY ANSWER Paternal exposure to BPA adversely affects spermatogenesis, several important sperm functions and DNA methylation patterns in spermatozoa, which have both multigenerational (in F0 and F1) and partial transgenerational (mainly noticed in F2, but F3) impacts on the fertility of the offspring. WHAT IS KNOWN ALREADY BPA, a synthetic endocrine disruptor, is used extensively to manufacture polycarbonate plastics and epoxy resins. Growing evidence suggests that exposure to BPA during the developmental stages results in atypical reproductive phenotypes that could persist for generations to come. STUDY DESIGN, SIZE, DURATION CD-1 male mice (F0) were treated with BPA (5 or 50 mg/kg body weight per day (bw/day)) or ethinylestradiol (EE) (0.4 μg/kg bw/day) for 6 weeks. Control mice were treated with vehicle (corn oil) only. The treated male mice were bred with untreated female mice to produce first filial generation (F1 offspring). The F2 and F3 offspring were produced similarly, without further exposure to BPA. PARTICIPANTS/MATERIALS, SETTING, METHODS Histological changes in the testis along with functional, biochemical and epigenetic (DNA methylation) properties of spermatozoa were investigated. Subsequently, each parameter of the F0–F3 generations was compared between BPA-treated mice and control mice. MAIN RESULTS AND THE ROLE OF CHANCE Paternal BPA exposure disrupted spermatogenesis by decreasing the size and number of testicular seminiferous epithelial cells, which eventually led to a decline in the total sperm count of F0–F2 offspring (P &lt; 0.05). We further showed that a high BPA dose decreased sperm motility in F0–F2 males by mediating the overproduction of reactive oxygen species (F0–F1) and decreasing intracellular ATP (F0–F2) in spermatozoa (P &lt; 0.05). These changes in spermatozoa were associated with altered global DNA methylation patterns in the spermatozoa of F0–F3 males (P &lt; 0.05). Furthermore, we noticed that BPA compromised sperm fertility in mice from the F0–F2 (in the both dose groups) and F3 generations (in the high-dose group only). The overall reproductive toxicity of BPA was equivalent to or higher (high dose) than that of the tested dose of EE. LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION Further research is required to determine the variables (e.g. lowest BPA dose) that are capable of producing changes in sperm function and fertility in future generations. WIDER IMPLICATIONS OF THE FINDINGS These results may shed light on how occupational exposure to BPA can affect offspring fertility in humans. STUDY FUNDING/COMPETING INTEREST(S) This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (Grant No. NRF-2018R1A6A1A03025159). M.S.R. was supported by Korea Research Fellowship Program through the NRF funded by the Ministry of Science and ICT (Grant No. 2017H1D3A1A02013844). There are no competing interests.


Drug Research ◽  
2020 ◽  
Vol 70 (09) ◽  
pp. 410-416
Author(s):  
Leila Etemad ◽  
Hadi Farkhari ◽  
Mohaddeseh Sadat Alavi ◽  
Ali Roohbakhsh

Abstract Objective Dihydromyricetin (DHM), a natural flavonoid, is used to reduce alcohol hangover. It has a modulatory role on GABAA receptors with significant effects on seizure and anxiety in animal models. We aimed to evaluate the effect of DHM on morphine conditioned place preference (CPP) and withdrawal sings following morphine dependence using animal models. Methods The effect of DHM (1, 2 and 5 mg/kg, intraperitoneal; ip) on the acquisition and expression of morphine-induced CPP was evaluated in male mice. Administration of morphine for three consecutive days induced physical dependence. The withdrawal signs such as jumping and defecation were precipitated by administration of naloxone (8 mg/kg, ip). The effect of DHM on the development of physical dependence was assessed by injection of DHM before morphine administrations. Results DHM, at the dose of 5 mg/kg, reduced expression of morphine CPP with an increase in the locomotor activity. DHM, at the doses of 2 and 5 mg/kg, also reduced development of morphine CPP. DHM alleviated development of morphine-induced physical dependence at the dose of 1, 2, and 5 mg/kg by decreasing jumping and defecation. Conclusion These results indicated that DHM decreased acquisition and expression of morphine CPP and inhibited development of morphine-induced physical dependence.


Endocrinology ◽  
2013 ◽  
Vol 154 (10) ◽  
pp. 3817-3825 ◽  
Author(s):  
Laura K. Fonken ◽  
Rebecca A. Lieberman ◽  
Zachary M. Weil ◽  
Randy J. Nelson

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