Paula Toni Del Giudice

Bio: Paula Toni Del Giudice is an academic researcher from Federal University of São Paulo. The author has contributed to research in topics: Sperm & Varicocele. The author has an hindex of 13, co-authored 13 publications receiving 521 citations.

Effect of varicocele on sperm function and semen oxidative stress

Abstract: Study Type – Aetiology (case control) Level of Evidence 3b What’s known on the subject? and What does the study add? Varicocele leads to alterations in sperm DNA integrity even when alterations in semen quality are not yet observed in adolescents. In adults, alterations to sperm DNA are associated to altered sperm morphology, indicating that altered spermatogenesis may be an important cause for the increased sperm DNA fragmentation observed in these men. One other important cause of increased DNA fragmentation is oxidative stress, and we wished to verify if this was the case. The study adds the information that, in the adult varicocele, it is most likely that an altered testicular environment is leading to increased DNA fragmentation and decreased mitochondrial activity and acrosome integrity, because no increase in oxidative stress was observed. OBJECTIVE • To assess the effect of varicocele on sperm DNA integrity, mitochondrial activity, lipid peroxidation and acrosome integrity. PATIENTS AND METHODS • In all, 30 patients with a clinically diagnosed varicocele of grade II or III and 32 men without a varicocele were evaluated for sperm DNA fragmentation (comet assay), mitochondrial activity (3,3′-diaminobenzidine assay), lipid peroxidation (malondialdehyde) and acrosome integrity (fluorescent probe labelled peanut agglutinin). RESULTS • The varicocele group showed fewer spermatozoa with intact DNA (grade II, P= 0.040), more cells with inactive mitochondria (class III, P= 0.001), fewer cells with active mitochondria (class I, P= 0.005) and fewer spermatozoa with intact acrosomes (P < 0.001). Finally, no significant differences were observed in lipid peroxidation levels. CONCLUSION • Men with varicocele showed an increase in sperm DNA fragmentation and a reduction in mitochondrial activity and acrosome integrity. However, lipid peroxidation levels remained unchanged.

Effect of leukocytospermia and processing by discontinuous density gradient on sperm nuclear DNA fragmentation and mitochondrial activity

Abstract: Purpose To assess the effect of leukocytospermia and semen processing on sperm DNA and mitochondria.

Unraveling the sperm proteome and post-genomic pathways associated with sperm nuclear DNA fragmentation

Abstract: Purpose Sperm DNA fragmentation has been suggested as a marker for infertility diagnosis and prognosis Hence, understanding its impact on male physiology and post-genomic pathways would be clinically important We performed the proteomics and functional enrichment analyses of viable spermatozoa from ejaculates with low and high sperm DNA fragmentation to identify protein expression and pathways altered in association with sperm DNA fragmentation

Analysis of the relationships between oxidative stress, DNA damage and sperm vitality in a patient population: development of diagnostic criteria

Abstract: BACKGROUND: DNA damage in human spermatozoa is known to be associated with a variety of adverse clinical outcomes affecting both reproductive efficiency and the health and wellbeing of the offspring. However, the origin of this damage, its biochemical nature and strategies for its amelioration, still await resolution. METHODS: Using novel methods to simultaneously assess DNA fragmentation (modified TUNEL assay), DNA-base adduct formation (8-hydroxy-2'-deoxyguanosine [80HdG]) and cell vitality, spermatozoa from a cohort of 50 assisted conception patients were examined and compared with a group of donors. Receiver operating characteristic (ROC) curve analysis was then used to examine the frequency distribution of the data and to determine optimized thresholds for identifying patients exhibiting abnormally high levels of DNA damage. RESULTS: BOHdG formation and DNA fragmentation were highly correlated with each other and frequently associated with cell death. Percoll centrifugation improved sperm quality but, unexpectedly, increased BOHdG formation in live cells, as did sperm fractionation using Puresperm ® gradients. ROC analysis indicated that the frequency distribution of 8OHdG and DNA fragmentation data were significantly different between patients and donors (P < 0.001), permitting the development of thresholds that would allow the accurate diagnosis of DNA damage in the male germ line. CONCLUSION: The aetiology of DNA damage in spermatozoa involves a cascade of changes that progress from the induction of oxidative stress and oxidized DNA base adduct formation to DNA fragmentation and cell death. Preparation of spermatozoa on discontinuous density gradients aggravates the problem by stimulating the formation of 8OHdG in live cells. However, the development of novel methods and optimized thresholds for diagnosing oxidative DNA damage in human spermatozoa should assist in the clinical management of this pathology.

Sperm DNA damage caused by oxidative stress: modifiable clinical, lifestyle and nutritional factors in male infertility.

Abstract: DNA fragmentation is an important factor in the aetiology of male infertility. However, it is still underevaluated and its inclusion in routine semen analysis is debated. DNA fragmentation has been shown to be a robust indicator of fertility potential, more so than conventional semen parameters. Men with high DNA fragmentation levels have significantly lower odds of conceiving, naturally or through procedures such as intrauterine insemination and IVF. Couples may be counselled to proceed directly to intracytoplasmic sperm injection as it is more successful in this group, avoiding costly procedures, recurrent failures or pregnancy losses; however, this treatment is not without limitations or risks. Ideally DNA fragmentation should be minimized where possible. Oxidative stress is the major cause of DNA fragmentation in spermatozoa. Endogenous and exogenous factors that contribute to oxidative stress are discussed, and in many cases are shown to be easily modifiable. Antioxidants play a protective role, although a delicate balance of reduction and oxidation is required for essential functions, including fertilization. Reducing oxidative stress may improve a couple's chances of conception either naturally or via assisted reproduction. Sources of oxidative stress therefore should be thoroughly examined in men with high levels of DNA fragmentation and modified where possible. DNA fragmentation is an important factor in the aetiology of male infertility. However it is still underevaluated and its inclusion in routine semen analysis is still debated. DNA fragmentation has been shown to be a robust indicator of fertility potential, more so than conventional semen parameters. Men with high levels of DNA fragmentation will have significantly lower odds of conceiving naturally or through procedures such as intrauterine insemination and IVF. Intracytoplasmic sperm injection (ICSI) may be much more successful in this group, and couples may be counselled to proceed directly to ICSI, avoiding costly procedures, recurrent failures or pregnancy losses. However, ICSI is not without its limitations or risks. Ideally, DNA fragmentation should be investigated and minimized where possible in men trying to conceive naturally or through assisted reproduction technology. Oxidative stress is the major cause of DNA fragmentation in spermatozoa. Endogenous and exogenous factors that contribute to oxidative stress are discussed and in many cases are easily modifiable. Antioxidants play a protective role, although a delicate balance of reduction and oxidation is required for essential sperm function, including fertilization. Reducing oxidative stress may improve a couple's chances of conception either naturally or via assisted reproduction treatment. Sources of oxidative stress therefore should be thoroughly examined in men with high levels of DNA fragmentation and modified where possible.

Oxidative stress and male infertility: current knowledge of pathophysiology and role of antioxidant therapy in disease management

Abstract: Infertility is a global health problem involving about 15% of couples. Approximately half of the infertility cases are related to male factors. The oxidative stress, which refers to an imbalance in levels of reactive oxygen species (ROS) and antioxidants, is one of the main causes of infertility in men. A small amount of ROS is necessary for the physiological function of sperm including the capacitation, hyperactivation and acrosomal reaction. However, high levels of ROS can cause infertility through not only by lipid peroxidation or DNA damage but inactivation of enzymes and oxidation of proteins in spermatozoa. Oxidative stress (OS) is mainly caused by factors associated with lifestyle. Besides, immature spermatozoa, inflammatory factors, genetic mutations and altering levels of sex hormones are other main source of ROS. Since OS occurs due to the lack of antioxidants and its side effects in semen, lifestyle changes and antioxidant regimens can be helpful therapeutic approaches to overcome this problem. The present study aimed to describe physiological ROS production, roles of genetic and epigenetic factors on the OS and male infertility with various mechanisms such as lipid peroxidation, DNA damage, and disorder of male hormone profile, inflammation, and varicocele. Finally, the roles of oral antioxidants and herbs were explained in coping with OS in male infertility.