Transgenerational inheritance of abnormal spermatogenesis with Igf2/H19 epigenetic alteration in CD1 mouse induced by in utero arsenic exposure

2020 ◽  
Author(s):  
Guoying Yin ◽  
Liting Xia ◽  
Yaxing Hou ◽  
Yaoyan Li ◽  
Deqing Cao ◽  
...  

AbstractDevelopmental exposure to environmental toxicants can induce transgenerational reproductive disease phenotypes through epigenetic mechanisms. However, little is known about the transgenerational effects of arsenic exposure. We hypothesize that prenatal arsenic exposure may result in impaired spermatogenesis in subsequent generations of male mice. To test our hypothesis, we treated pregnant CD-1 (F0) mice with drinking water containing sodium arsenite (85 ppm) from days 8 to 18 of gestation. Male offspring were bred with untreated female mice until the F3 generation was produced. Our results revealed that transient exposure of the F0 gestating female to arsenic can result in decreased sperm quality and histological abnormalities in testes of male offspring in the F1 and F3 generations. The overall methylation status of Igf2 DMR2 and H19 DMR was significantly lower in the arsenic-exposed group than that of the control group in both F1 and F3 generations. The relative mRNA expression levels of Igf2 and H19 in arsenic-exposed males were significantly higher than in the control males in both F1 and F3 generations. This study indicates that ancestral exposure to arsenic may result in transgenerational inheritance of an impaired spermatogenesis phenotyping involving both epigenetic alterations and the abnormal expression of Igf2 and H19.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lydia Enith Nava-Rivera ◽  
Nadia Denys Betancourt-Martínez ◽  
Rodrigo Lozoya-Martínez ◽  
Pilar Carranza-Rosales ◽  
Nancy Elena Guzmán-Delgado ◽  
...  

AbstractAn emerging concern is the influences of early life exposure to environmental toxicants on offspring characteristics in later life. Since recent evidence suggests a transgenerational transference of aberrant phenotypes from exposed-parents to non-exposed offspring related to adult-onset diseases including reproductive phenotype. The transgenerational potential of arsenic a well know genotoxic and epigenetic modifier agent has not been assessed in mammals until now. In this experimental study, we evaluated the transgenerational effects of arsenic in a rat model with chronic exposure to arsenic. Rats chronically exposed to arsenic in drinking water (1 mg As2O3/mL) (F0) were mated to produce the arsenic lineage (F1, F2, and F3). The arsenic toxic effects on were evaluated over the four generations by analyzing the DNA methylation percentage, genotoxicity in WBC and physical and reproductive parameters, including sperm quality parameters and histopathological evaluation of the gonads. Chronic exposure to arsenic caused genotoxic damage (F0–F3) different methylation patterns, alterations in physical and reproductive parameters, aberrant morphology in the ovaries (F0 and F1) and testicles (F1–F3), and a decrease in the quality of sperm (F0–F3, except F2). Parental chronic arsenic exposure causes transgenerational genotoxicity and changes in global DNA methylation which might be associated with reproductive defects in rats. Combined with recent studies reveal that disturbances in the early life of an individual can affect the health of later generations.


2009 ◽  
Vol 21 (5) ◽  
pp. 634 ◽  
Author(s):  
Renata C. Piffer ◽  
Patrícia C. Garcia ◽  
Daniela C. C. Gerardin ◽  
Wilma G. Kempinas ◽  
Oduvaldo C. M. Pereira

The present study investigated the long-term effects of prenatal betamethasone exposure on sperm quality and count, fertility and plasma testosterone levels in adult male rats. Pregnant rats received 0.1 mg kg–1 betamethasone on Days 12, 13, 18 and 19 of pregnancy. This treatment impaired sperm quality, sperm production, fertility and plasma testosterone levels in adult male offspring compared to the control group. Thus, the results of the present study indicate that the long-term effects of prenatal betamethasone exposure may be deleterious to offspring. The consequent decrease in testosterone production during adulthood, in association with damaged semen parameters, may explain for the observed decrease in the capacity of adult male offspring to themselves generate viable descendants.


2020 ◽  
Vol 20 (2) ◽  
pp. 198-202 ◽  
Author(s):  
Mohammad Motamedifar ◽  
Yalda Malekzadegan ◽  
Parisa Namdari ◽  
Behzad Dehghani ◽  
Bahia Namavar Jahromi ◽  
...  

Introduction: Infertility considered as a social and public health issue and estimated that most of these infertile couples are residents of developing countries. Infectious diseases including the history of Sexually Transmitted Infections (STIs) may impact on male reproductive function. Therefore, the present study aimed to investigate the prevalence of bacterial contaminants of semen and probable association with sperm quality of infertile men in Iranian population. Methods: The study population consisted of 200 infertile men and 150 fertile men attending an infertility Center in southwestern Iran during the study period in 2015. The assessment of sperm parameters was according to the World Health Organization (WHO) guidelines. The presumptive pathogens were identified using standard microbiology tests and confirmed by specific PCR primers. Results: The prevalence of bacteriospermia in the semen of the infertile group was significantly higher than that in the fertile group (48% vs. 26.7%, P <0.001). The microbiological analysis of samples showed that the most abundant species of bacteria in semen of infertile men were Chlamydia trachomatis (12.5%) followed by Neisseria gonorrhoeae (11%). On the other hand, in the control group, Lactobacillus spp. (17.3%) was the most isolated pathogen. Results showed that the presence of N. gonorrhoeae, C. trachomatis, Mycoplasma genitalium, Haemophilus, and Klebsiella was significantly associated with sperm abnormality. Conclusion: Based on our findings, it seems that bacteriospermia is associated with alterations in the properties of semen which may lead to a decrease in the fertilization potential of sperm. Therefore, immediate and appropriate treatment is necessary before investigating every other possible cause of infertility.


Author(s):  
Mai Mahmoud Shaker ◽  
Taghreed Abdelmoniem shalabi ◽  
Khalda said Amr

Abstract Background DNA methylation is an epigenetic process for modifying transcription factors in various genes. Methylenetetrahydrofolate reductase (MTHFR) stimulates synthesis of methyl radical in the homocysteine cycle and delivers methyl groups needed in DNA methylation. Furthermore, numerous studies have linked gene polymorphisms of this enzyme with a larger risk of recurrent pregnancy loss (RPL), yet scarce information is available concerning the association between epigenetic deviations in this gene and RPL. Hypermethylation at precise DNA sequences can function as biomarkers for a diversity of diseases. We aimed by this study to evaluate the methylation status of the promoter region of MTHFR gene in women with RPL compared to healthy fertile women. It is a case–control study. Hundred RPL patients and hundred healthy fertile women with no history of RPL as controls were recruited. MTHFR C677T was assessed by polymerase chain reaction-restriction fragment length polymorphism (RFLP). Quantitative evaluation of DNA methylation was performed by high-resolution melt analysis by real-time PCR. Results The median of percentage of MTHFR promoter methylation in RPL cases was 6.45 [0.74–100] vs. controls was 4.50 [0.60–91.7], P value < 0.001. In the case group, 57 hypermethylated and 43 normo-methylated among RPL patients vs. 40 hypermethylated and 60 normo-methylated among controls, P< 0.005. Frequency of T allele in C677T MTHFR gene among RPL patients was 29% vs. 23% among the control group; C allele vs. T allele: odds ratio (OR) = 1.367 (95% confidence interval (CI) 0.725–2.581). Conclusion Findings suggested a significant association between hypermethylation of the MTHFR promoter region in RPL patients compared to healthy fertile women.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii186-ii186
Author(s):  
O’Dell Patrick ◽  
H Nickols ◽  
R LaRocca ◽  
K Sinicrope ◽  
D Sun ◽  
...  

Abstract BACKGROUND Patients who have recurrent glioblastoma have limited treatment options. We conducted a retrospective review of patients with recurrent glioblastoma treated with standard initial radiation and temozolomide with tumor treating fields to investigate whether reirradiation using radiosurgery would be associated with improved outcomes. METHODS We reviewed the records of 54 consecutively treated patients with recurrent glioblastoma with ECOG 0 or 1 at recurrence and conducted Kaplan-Meier analysis with Log-rank testing to determine significance between groups. RESULTS We identified 24 patients who were treated without radiation therapy (control) while 30 patients underwent re-irradiation using radiosurgery (ReSRS) with a median total dose of 25Gy in five fractions. All patients had completed standard initial therapy, and there was no difference in the time to recurrence between the two groups (10 months for control, 15 months for ReSRS, [P = 0.17, HR for progression 0.65 (95% CI 0.38-1.13)]. A larger proportion of patients in the control arm (54%) had subtotal or gross total resection of the recurrence compared with the ReSRS group (44%, P &lt; 0.05). The majority of patients had recurrence confirmed with biopsy (18/22 in control group, 25/31 in the ReSRS group). MGMT methylation status did not differ between control vs ReSRS (29% vs. 27%). ReSRS was associated with improved median survival from the time of first recurrence of 11.6 months versus 3.8 months in the control arm [P&lt; 0.0001, HR for death 0.33 (95% CI 0.18-0.6)]. CONCLUSIONS In a group of patients with high performance status diagnosed with recurrent glioblastoma, reirradiation with stereotactic radiosurgery was associated with nearly one year median survival after recurrence. Additional analyses are warranted to determine the impact of concurrent systemic therapies with irradiation and underlying tumor or patient factors to predict outcomes.


2016 ◽  
Vol 28 (8) ◽  
pp. 1206 ◽  
Author(s):  
Aline C. Ramos ◽  
Alice H. dos Santos ◽  
Kennia M. Silveira ◽  
Ana Carolina I. Kiss ◽  
Suzana F. P. Mesquita ◽  
...  

Fluoxetine (FLX) is a selective serotonin reuptake inhibitor (SSRI) antidepressant commonly prescribed during pregnancy and lactation. Pre- and post-partum depression, as well as SSRI treatment during these periods, may change maternal care, interfering with offspring development. Moreover, it is known that SSRIs may alter testes structure and function in offspring. The present study investigated the effects of maternal FLX exposure on maternal behaviour and testes function in offspring. Female Wistar rats were treated with 7.5 mg kg–1 FLX or tap water (control group) by gavage from the Day 1 of pregnancy until 21 days after birth (postnatal Day (PND) 21). Maternal behaviour was evaluated and morphofunctional analyses of offspring testes were conducted on PND 21 and 50. There were no significant differences between the FLX-treated and control groups regarding maternal behaviour. Nor did maternal treatment with FLX have any effect on bodyweight gain, anogenital distance, day of preputial separation, testis weight and the gonadosomatic index in male offspring. However, there was a decreased number of Sertoli cells at both PND 21 and 50 in FLX-exposed male offspring. The findings of the present study demonstrate that maternal exposure to FLX can impair testicular function in weanling and pubertal animals.


2021 ◽  
Vol 20 (4) ◽  
pp. 768-773
Author(s):  
Meidona Nurul Milla ◽  
Yani Istadi ◽  
Vania Shaula ◽  
Deastri Anjeas Wari ◽  
Chntyia Dwi Cahyani Puspitasari ◽  
...  

Background: Infertility has been more common problems among couple of reproductive age. One of the factors causing this disorder is unhealthy environmental factors including exposure to cigarette smoke. Polynuclear aromatic hydrocarbons (PAHs) in cigarette smoke can cause testicular atrophy, while the free radicals can inhibit the stages of spermatogenesis, and nicotine in cigarettes affects the brain dopamine levels affecting the levels of GnRH, and subsequently affect the levels of FSH and LH needed in spermatogenesis. The use of Mucuna pruriens seed extract containing antioxidants and L-dopa is expected to improve the quality of sperm after exposure to cigarette smoke. Objective: This study aimed to determine the effect of Mucuna pruriens seed extract on the sperm quality in mice exposed to cigarette smoke. Methods: This study was an experimental study with a post test only control group design. A total of 20 mice were divided into 4 groups of five mice each. All groups were exposed to cigarette smoke. Group 1 was the negative control exposed to cigarette smoke. Groups 2, 3, 4 were exposed to cigarettes smoke and given Mucuna pruriens seed extracts at the dose of 250; 300; and 350 mg/Kg BW/day. Parameters of sperm quality included concentration, morphology, motility and viability. Results: Post hoc tests showed there were significant differences among treatment groups. Conclusion: the administration of Mucuna pruriens seed extract affects the sperm quality of BALB/c mice exposed to cigarettes smoke. Bangladesh Journal of Medical Science Vol.20(4) 2021 p.768-773


2021 ◽  
pp. 39-45
Author(s):  
Nura I. Al-Zail ◽  
Salah F. Kamies

Pyrethroid cyhalothrin (PC) is an insecticide that is used worldwide for pest control in agriculture and household use. Samoa extract (SE) is a potent antioxidant protecting cells from oxidative stress. The present study investigates the protective and therapeutic effect of SE on PC-induced changes in sperm quality in male rats. Fifty adult male albino rats were divided into five groups: group I: served as control; group II: received PC i.p. only (6.2 mg/kg b.wt.); group III: received SE only (100 mg/kg b.wt., p.o.) for eight weeks; group IV: received SE as a protective agent daily for eight weeks, then followed by the administration of PC (i.p.) three times a week for two weeks; group V: exposed to PC (i.p.) three times a week for two weeks, then treated with the SE daily for 8 weeks. Results showed that PC caused markedly impaired sperm quality (a count, viability, motility, and abnormality). Compared to PC-treated animals, SE in the protective group markedly restored the alteration of sperm indices. However, SE in the curative group was found to be less effective in restoring PC-induced alterations. In conclusion, the data of this study revealed that the SE as a protective agent is more effective than as a therapeutic agent. Keywords: Samoa; Pyrethroid; Sperm quality; Rat


Nutrients ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1407 ◽  
Author(s):  
You-Lin Tain ◽  
Julie Chan ◽  
Chien-Te Lee ◽  
Chien-Ning Hsu

Although pregnant women are advised to consume methyl-donor food, some reports suggest an adverse outcome. We investigated whether maternal melatonin therapy can prevent hypertension induced by a high methyl-donor diet. Female Sprague-Dawley rats received either a normal diet, a methyl-deficient diet (L-MD), or a high methyl-donor diet (H-MD) during gestation and lactation. Male offspring were assigned to four groups (n = 7–8/group): control, L-MD, H-MD, and H-MD rats were given melatonin (100 mg/L) with their drinking water throughout the period of pregnancy and lactation (H-MD+M). At 12 weeks of age, male offspring exposed to a L-MD or a H-MD diet developed programmed hypertension. Maternal melatonin therapy attenuated high methyl-donor diet-induced programmed hypertension. A maternal L-MD diet and H-MD diet caused respectively 938 and 806 renal transcripts to be modified in adult offspring. The protective effects of melatonin against programmed hypertension relate to reduced oxidative stress, increased urinary NO2− level, and reduced renal expression of sodium transporters. A H-MD or L-MD diet may upset the balance of methylation status, leading to alterations of renal transcriptome and programmed hypertension. A better understanding of reprogramming effects of melatonin might aid in developing a therapeutic strategy for the prevention of hypertension in adult offspring exposed to an excessive maternal methyl-supplemented diet.


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