scholarly journals Effects of paternal overnutrition and interventions on future generations

Author(s):  
Md Mustahsan Billah ◽  
Saroj Khatiwada ◽  
Margaret J. Morris ◽  
Christopher A. Maloney

AbstractIn the last two decades, evidence from human and animal studies suggests that paternal obesity around the time of conception can have adverse effects on offspring health through developmental programming. This may make significant contributions to the current epidemic of obesity and related metabolic and reproductive complications like diabetes, cardiovascular disease, and subfertility/infertility. To date, changes in seminal fluid composition, sperm DNA methylation, histone composition, small non-coding RNAs, and sperm DNA damage have been proposed as potential underpinning mechanism to program offspring health. In this review, we discuss current human and rodent evidence on the impact of paternal obesity/overnutrition on offspring health, followed by the proposed mechanisms, with a focus on sperm DNA damage underpinning paternal programming. We also summarize the different intervention strategies implemented to minimize effects of paternal obesity. Upon critical review of literature, we find that obesity-induced altered sperm quality in father is linked with compromised offspring health. Paternal exercise intervention before conception has been shown to improve metabolic health. Further work to explore the mechanisms underlying benefits of paternal exercise on offspring are warranted. Conversion to healthy diets and micronutrient supplementation during pre-conception have shown some positive impacts towards minimizing the impact of paternal obesity on offspring. Pharmacological approaches e.g., metformin are also being applied. Thus, interventions in the obese father may ameliorate the potential detrimental impacts of paternal obesity on offspring.

2019 ◽  
Vol 101 (4) ◽  
pp. 748-759 ◽  
Author(s):  
Emily R Bryan ◽  
Avinash Kollipara ◽  
Logan K Trim ◽  
Charles W Armitage ◽  
Alison J Carey ◽  
...  

Abstract The incidence of Chlamydia infection, in both females and males, is increasing worldwide. Male infections have been associated clinically with urethritis, epididymitis, and orchitis, believed to be caused by ascending infection, although the impact of infection on male fertility remains controversial. Using a mouse model of male chlamydial infection, we show that all the major testicular cell populations, germ cells, Sertoli cells, Leydig cells, and testicular macrophages can be productively infected. Furthermore, sperm isolated from vas deferens of infected mice also had increased levels of DNA damage as early as 4 weeks post-infection. Bilateral vasectomy, prior to infection, did not affect the chlamydial load recovered from testes at 2, 4, and 8 weeks post-infection, and Chlamydia-infected macrophages were detectable in blood and the testes as soon as 3 days post-infection. Partial depletion of macrophages with clodronate liposomes significantly reduced the testicular chlamydial burden, consistent with a hematogenous route of infection, with Chlamydia transported to the testes in infected macrophages. These data suggest that macrophages serve as Trojan horses, transporting Chlamydia from the penile urethra to the testes within 3 days of infection, bypassing the entire male reproductive tract. In the testes, infected macrophages likely transfer infection to Leydig, Sertoli, and germ cells, causing sperm DNA damage and impaired spermatogenesis.


Andrologia ◽  
2011 ◽  
Vol 44 ◽  
pp. 642-649 ◽  
Author(s):  
J. Varshini ◽  
B. S. Srinag ◽  
G. Kalthur ◽  
H. Krishnamurthy ◽  
P. Kumar ◽  
...  

2019 ◽  
Vol 90 (4) ◽  
pp. 254-259 ◽  
Author(s):  
Alessandro Colasante ◽  
Maria Giulia Minasi ◽  
Filomena Scarselli ◽  
Valentina Casciani ◽  
Vincenzo Zazzaro ◽  
...  

Objective: the aim of our study was to put forward insights to treat any possible correlation among sperm quality, sperm DNA damage and male age as they may have fertility implications for men who choose to delay fatherhood. Materials and methods: Our study is a non-interventional retrospective analysis of 3124 semen samples from patients that were investigated for the conventional semen parameters. Tunel test assay was set up for the evaluation of the sperm DNA fragmentation index (DFI). We applied the Kappa index to compare both the 1999 and the 2010 World Health Organization (WHO) reference criteria to evaluate the competence of such semen parameters categorization during the standard routine of our laboratory. Results: With regards to our findings, it is possible to underline a significant relationship between aging and semen volume (p = 0.001), motility (p = 0.009), semen viscosity (p < 0.003) and sperm DNA damage (p < 0.009). We found a trend when focusing on the semen concentration (p = 0.05). The analysis of sperm morphology did not show any influence with advancing age (p = 0.606). When comparing both the 1999 and the 2010 WHO scales we found no accordance in the appraisal of sperm morphology but a very good one in the evaluation of the other parameters. Conclusions: Conventional semen analysis represents the opportunity to draw up a proxy insight on the male fertility status even if semen quality can only indirectly assess the probability of pregnancy. Several studies have verified a decay in the male reproductive system, sperm quality and fertility with advancing age although the reported results are not yet conclusive. Our results substantially agree with those findings outlined in the literature. Moreover we find that the discrepancy between the two WHO reference scales would eventually lead to an improper diagnosis of infertility.


2019 ◽  
Vol 15 (2) ◽  
pp. e58-e65
Author(s):  
Saad Alshahrani ◽  
Gulfam Ahmad ◽  
Haroon Latif Khan ◽  
Ahmet Ayaz ◽  
Ali Hassan A. Ali

Background and objective The aim of the present study was to identify the impact of defective standard sperm parameters individually and in combination on DNA damage in a large cohort of infertile men. Material and methods Retrospective analysis of semen characteristics was conducted on 436 patients. DNA fragmentation analysis was performed by using the terminal deoxynucleotidyl transferase (TdT)-mediated fluoresce-in-dUTP nick end labeling (TUNEL) assay. Sperm parameters were arranged into different categories such as normospermia asthenospermic, teratospermic, asthenoteratospermic, and oligoasthenoteratospermic. GraphPad Prism version 7 software was used for data analysis. Results Our results suggest that the mean percentage of DNA damage was proportionally higher than the semen abnormalities. Sperm with 3 abnormal parameters showed significantly higher DNA damage, suggesting that sperm having more than 2 abnormalities are more likely to have higher DNA damage. Conclusion Sperm motility had significant correlation and is supposed to be a predictor for these tests, while morphology was the second standard sperm parameter inversely correlated with sperm DNA damage. Patients demonstrating low levels of leukocytospermia should be advised sperm DNA testing before assisted reproductive technology treatment. However, there is a clear need for more research studies to further address these issues.    


Author(s):  
Ahmed T Alahmar ◽  
Pallav Sengupta ◽  
Sulagna Dutta ◽  
Aldo E. Calogero

Objective: Oxidative stress (OS) plays a key role in the etiology of unexplained male infertility. Coenzyme Q10 (CoQ10) is a potent antioxidant that may improve semen quality and OS in infertile men with idiopathic oligoasthenoteratospermia (OAT), but the underlying mechanism is unknown. Therefore, the present study was undertaken to investigate the effect of CoQ10 on OS markers and sperm DNA damage in infertile patients with idiopathic OAT. Methods: This prospective controlled study included 50 patients with idiopathic OAT and 50 fertile men who served as controls. All patients underwent a comprehensive medical assessment. Patients and controls received 200 mg of oral CoQ10 once daily for 3 months. Semen and blood were collected and analyzed for sperm parameters, seminal CoQ10 levels, reactive oxygen species (ROS) levels, total antioxidant capacity, catalase, sperm DNA fragmentation (SDF), and serum hormonal profile. Results: The administration of CoQ10 to patients with idiopathic OAT significantly improved sperm quality and seminal antioxidant status and significantly reduced total ROS and SDF levels compared to pre-treatment values. Conclusion: CoQ10, at a dose of 200 mg/day for 3 months, may be a potential therapy for infertile patients with idiopathic OAT, as it improved sperm parameters and reduced OS and SDF in these patients.


2019 ◽  
Vol 34 (10) ◽  
pp. 1915-1923 ◽  
Author(s):  
James Nicopoullos ◽  
Andrew Vicens-Morton ◽  
Sheena E M Lewis ◽  
Kathryn Lee ◽  
Peter Larsen ◽  
...  

Abstract STUDY QUESTION Do the Comet parameters of the proportions of sperm with low or high DNA damage improve the power of the test in the diagnosis of male infertility and/or prediction of IVF and ICSI live birth rates? SUMMARY ANSWER The mean Comet score and the scores for proportions of sperm with high or low DNA damage were useful in diagnosing male infertility and provided additional discriminatory information for the prediction of both IVF and ICSI live births. WHAT IS KNOWN ALREADY Sperm DNA damage impacts adversely on male fertility and IVF outcomes. STUDY DESIGN, SIZE, DURATION A retrospective study was performed involving a total of 457 participants (381 patients and 76 fertile donors). Data was collected from a fertility clinic between 2015 and 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 381 consecutive male partners of couples attending for ART and 76 fertile donors were included in the study. DNA fragmentation was measured by the alkaline Comet assay. Receiver operator characteristic curve analysis (area under the ROC curve (AUC)) was used to determine the value of average Comet score (ACS), low Comet score (LCS) and high Comet score (HCS) to diagnose male factor infertility. In total, 77 IVF and 226 ICSI cycles were included to determine thresholds for each parameter (AUC analysis) and to compare live birth rates (LBRs) following each ART. MAIN RESULTS AND THE ROLE OF CHANCE ACS, HCS and LCS were predictive of male infertility (AUC > 0.9, P < 0.0001). IVF LBRs declined once DNA damage exceeded the threshold levels. HCS showed the sharpest decline. Following ICSI, the highest LBRs were in men whose DNA damage levels approached the fertile range. Trends differed in IVF. LBRs decreased as damage increased whereas in ICSI the LBRs decreased but then remained stable. LIMITATIONS, REASONS FOR CAUTION Since this is the first study to show the impact of sperm DNA damage on ICSI live births, a prospective study should be performed (stratifying patients to IVF or ICSI based on these thresholds) to validate this study. WIDER IMPLICATIONS OF THE FINDINGS Our study presents novel information towards elucidating the genetic basis of male infertility and secondly on relevance of the extent of DNA damage as an impending factor in both IVF and ICSI success. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by Examenlab Ltd, The Lister Clinic, Cryos International and Imperial College London NHS Trust. No external funding was obtained for this study. SL and KL are employees of Examenlab Ltd, a university spin-out company with a commercial interest in sperm DNA damage. No other author has a conflict of interest to declare. TRIAL REGISTRATION NUMBER Non-applicable.


2013 ◽  
Vol 27 (4) ◽  
pp. 325-337 ◽  
Author(s):  
Sheena E.M. Lewis ◽  
R. John Aitken ◽  
Sarah J. Conner ◽  
Geoffry De Iuliis ◽  
Donald P. Evenson ◽  
...  

Author(s):  
Ilyas Yusuf ◽  
Mathias Abiodun Emokpae

Background: Studies have shown oxidative DNA damage is associated with male infertility. Objective: This study determines the levels of 8-hydroxy-2’-deoxyguanosine (8-OHdG) and some markers of oxidative stress in seminal fluid of males investigated for infertility and men of proven fertility in Benin City, Nigeria. Materials and Methods: Semen samples produced by self or assisted masturbation were analyzed by microscopic technique according to the World Health Organization guidelines. Thereafter, samples were centrifuged and seminal fluid plasma separated and stored at -20°C prior to assay for 8-OHdG and oxidative stress biomarkers. Based on the sperm concentration/count, the overall samples were grouped into the following categories: normospermia (n = 20), oligozoospermia (n = 30), and azoospermia (n = 20). The control group comprised of 30 age-matched males of proven fertility. The seminal fluid 8-OHdG, total antioxidant status, superoxide dismutase and malondialdehyde (MDA) were assayed through ELISA and spectrophotometric methods, respectively. Results: Seminal plasma level of 8-OHdG and MDA were significantly higher (p = 0.01) in infertile subjects than controls. The mean levels of 8-OHdG and MDA in infertile subjects were higher in azoospermia than oligospermia than normospermia and so, was least in the normospermia. Conversely, the mean levels of total antioxidant status and superoxide dismutase were significantly lower (p = 0.01) in infertile than fertile the control male subjects with levels higher in normospermia than oligospermia and least in azoospermia. Moreover, the seminal 8-OHdG correlated negatively with sperm count (r = -0.359, p = 0.01), percent motility (r = -0.388, p = 0.04), and percent morphology (r = -0.327, p = 0.02). Conclusion: The assessment of sperm DNA damage in addition to routine seminal fluid analysis may play an important role in specific diagnosis and management of male infertility. Key words: Male, Semen, Antioxidants, Sperm count, DNA damage.


2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Valeria Maria Iommiello ◽  
Elena Albani ◽  
Alessandra Di Rosa ◽  
Alessandra Marras ◽  
Francesca Menduni ◽  
...  

Oxidative stress (OS) plays an essential role in male infertility aetiology by affecting sperm quality, function, and also the integrity of sperm DNA. The assessment of oxidative stress in semen may be an important tool to improve the evaluation of sperm reproductive capacity. The purpose of this study was the evaluation of any possible relation between the unbalance of oxidative stress caused by superoxide anion in the ejaculate with the presence of sperm DNA fragmentation and high concentration of round cells. 56 semen samples from males from couples suffering from infertility were evaluated according to World Health Organisation (WHO) 2010 guidelines. Oxidative stress levels from N1 (low) to N4 (high) were assessed in ejaculates using oxiSperm; DFI (sperm DNA fragmentation index) as assessed by the SCSA (Sperm Chromatin Structure Assay) was used for evaluation of sperm chromatin integrity. Our data show that high oxidative stress (N3-N4 levels) correlated positively with aDFI≥30%(P=0.0379)and round cells≥1.500.000/mL(P=0.0084). In conclusion, OS increases sperm DNA damage. Thus evaluation of semen OS extent of sperm DNA damage in infertile man could be useful to develop new therapeutic strategies and improve success of assisted reproduction techniques (ART).


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