Sperm redox biology challenges the role of antioxidants as a treatment for male factor infertility

Caroppo, Ettore; Dattilo, Maurizio

doi:10.1016/j.xfnr.2021.12.001

Cited by 10 publications

(9 citation statements)

References 88 publications

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“…We found that vital SDF was significantly associated with ORP. The fact that no correlation was found between ORP and total SDF is in line with the recent review by Caroppo and Datillo, stating that double-strand breaks are mainly associated with defective histone to protamine transition, and not with oxidative damage [ 68 ]. Moreover, sperm chromatin parameters reveal a low correlation with standard semen parameters, suggesting that these reflect completely different physiological processes during spermatogenesis [ 55 ].…”

Section: Discussionsupporting

confidence: 81%

Sperm as a Carrier of Genome Instability in Relation to Paternal Lifestyle and Nutritional Conditions

et al. 2022

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Endogenous and exogenous factors can severely affect the integrity of genetic information by inducing DNA damage and impairing genome stability. The extent to which men with and without subfertility are exposed to several adverse lifestyle factors and the impact on sperm DNA fragmentation (SDF), sperm chromatin maturity (condensation and decondensation), stability (hypo- and hypercondensation) and sperm aneuploidy are assessed in this study. Standardized assays employing flow cytometry were used to detect genome instability in 556 samples. Semen parameters deteriorated with age, BMI, increased physical activity and smoking. Age and BMI were associated with increased SDF. Increased BMI was associated with increased hypocondensed chromatin and decreased decondensed chromatin. Increase in age also caused an increase in sex chromosome aneuploidy in sperms. Surprisingly, alcohol abuse reduced chromatin hypercondensation and drug abuse reduced SDF. Although genome instability was more pronounced in the subfertile population as compared to the fertile group, the proportion of men with at least one lifestyle risk factor was the same in both the fertile and subfertile groups. While one in three benefited from nutritional supplementation, one in five showed an increase in SDF after supplementation. Whilst the message of ‘no smoking, no alcohol, no drugs, but a healthy diet’ should be offered as good health advice, we are a long way from concluding that nutritional supplementation would be beneficial for male fertility.

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Section: Discussionsupporting

confidence: 81%

Sperm as a Carrier of Genome Instability in Relation to Paternal Lifestyle and Nutritional Conditions

et al. 2022

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“…Therefore, the prediabetic state through reductive stress can results in increase in ROS level assessed by DCF (see Figure 4) and account for lipid peroxidation and DNA damage. In addition, for proper chromatin condensation through transition of histones with protamines, NAD is required for repairing double strand breaks by PARP enzyme and shortage of NAD in reductive stress condition, may lead unrepaired double‐strand breaks which may have serve consequence of developmental competency of embryos (Caroppo & Dattilo, 2022). Reductive stress also induces hypoxia as oxygen is used for production of superoxide and exercise may aggravate this state as stated above.…”

Section: Discussionmentioning

confidence: 99%

“…Reductive stress also induces hypoxia as oxygen is used for production of superoxide and exercise may aggravate this state as stated above. Regarding increase motility, Caroppo & Dattilo, 2022 in a recent review paper in journal Fertility and Sterility state that “Mechanisms regulating sperm motility do not involve the redox balance, and the role of mitochondria in sperm bioenergetics is controversial” (Caroppo & Dattilo, 2022). Therefore, other mechanism may account for increased sperm motility, like glycolysis, that also account for increased NADPH in reductive stress.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies stated, similar to “oxidative stress “condition, the level of ROS is also increased in the “reductive stress” condition. Furthermore, in “reductive stress” the ratio of NAD+/NADH, NADP+/NADPH and, GSH/GSSG substantial increase and in the mitochondria instead of transferring electron to components of electron transport chain, the electron has higher tendency to be transferred to oxygen and lead to formation of superoxide, and therefore ROS level (Caroppo & Dattilo, 2022; Yan, 2014).…”

Section: Discussionmentioning

confidence: 99%

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The effect of green coffee and/or endurance exercise on sperm function in pre‐diabetic mice

et al. 2022

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This study aimed to investigate the effect of green coffee (GC), chlorogenic acid (CA) as an active ingredient of GC and exercise, alone or in a combination with exercise, on spermatogenesis and sperm function in pre‐diabetic mice. Results revealed that pre‐diabetic status can have a significant adverse effect on spermatogenesis (Johnson score), and sperm concentration, motility, DNA damage and persistent histone in compared to the control group. Although lipid peroxidation, intracellular ROS production, and persistent histones in sperm were high in pre‐diabetic mice, exercise only can improve sperm motility. GC alone only improved sperm motility in pre‐diabetic mice while CA alone, even did not have this beneficial effect. However, GC along with exercise, did not improve motility but reduce DNA damage, while CA with exercise, significantly improved motility compared to pre‐diabetic stage and to the level comparable to control. Therefore, based on this result in individuals with high DNA damage, GC supplementation and exercise could be useful approach while in asthenozoospermia, CA supplementation and exercise should be considered as an alternative approach. However, such an interpretation awaits validation.

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“…Важно, что расстройства сперматогенеза является самым частым показанием для приема антиоксидантов. По данным клинических исследований, эмпирическая терапия такого рода приводит к неубедительным или отрицательным результатам [40][41][42]…”

Section: Reviewunclassified

The role of sperm mitochondria in the occurrence and development of male infertility

Литвицкий¹,

Галимов²,

Громенко³

et al. 2022

Zhurnal «Patologicheskaia Fiziologiia I Eksperimental`naia Terapiia»

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Цель обзора - анализ современных данных о роли митохондрий сперматозоидов в возникновении и развитии репродуктивных форм патологии. Митохондрии занимают центральное место в метаболизме сперматозоидов. Это обусловлено их участием в синтезе макроэргических фосфатов и поддержании окислительно-восстановительного потенциала; регуляции скорости их пролиферации, дифференцировки, апоптоза и митофагии; генерации активных форм кислорода; реализации внутриклеточного сигналинга и других процессов, обеспечивающих подвижность жгутиков, капацитацию, акросомальную реакцию, активацию ооцитов и слияние гамет. В большинстве случаев изменения этих функций ассоциированы с субфертильностью и/или бесплодием. Продемонстрирована также тесная связь между митохондриальным геномом, протеомом, метаболомом и оплодотворяющей способностью сперматозоидов. Выявлены ключевые белки митохондрий (АТФ-синтаза, аденилаттранслоказа, аденилаткиназа 1, изоцитратдегидрогеназа 3β, аконитатгидратаза, фумаратгидратаза, пируватдегидрогеназный комплекс, сиртуины, пероксиредоксины и др.), участвующие в репродуктивном процессе. Показана корреляция аберрантной экспрессии генов этих белков с ухудшением качественных и количественных характеристик эякулята. Доказана облигатная роль в метаболизме сперматозоидов таких энергетических субстратов митохондрий как лактат и длинноцепочечные жирные кислоты. Вместе с тем, высокая пластичность митохондрий, сравнительно легко модулирующих свою локализацию, форму и метаболическую активность, затрудняет однозначную интерпретацию имеющегося в настоящее время массива фактических данных об их функциях. Расшифровка молекулярно-генетических механизмов нарушения структуры митохондрий и их дисфункции может стать основой для разработки эффективных методов диагностики и таргетной терапии мужского бесплодия. The aim of this review was to analyze current data on the role of sperm mitochondria in the occurrence and development of reproductive pathologies. Mitochondria play a major role in the sperm metabolism due to their participation in the synthesis of high-energy phosphates; maintenance of redox potential; regulation of the sperm proliferation rate, differentiation, apoptosis, and mitophagy; generation of reactive oxygen species; implementation of intracellular signaling, and other processes that ensure flagella motility, capacitation, acrosomal reaction, oocyte activation, and gamete fusion. In most cases, changes in these functions are associated with subfertility and/or infertility. A close relationship between the mitochondrial genome, proteome, metabolome, and sperm fertility has also been demonstrated. The key mitochondrial proteins (ATP synthase, adenylate translocase, adenylate kinase 1, isocitrate dehydrogenase 3β, aconitate hydratase, fumarate hydratase, pyruvate dehydrogenase complex, sirtuins, peroxiredoxins, etc.) involved in the reproductive process were identified. Correlations were found between the aberrant gene expression of these proteins and the deterioration of qualitative and quantitative characteristics of the ejaculate. The obligate role in sperm metabolism of mitochondrial energy substrates, such as lactate and long-chain fatty acids, has been proved. At the same time, the high plasticity of mitochondria, which relatively easily modulate their localization, shape, and metabolic activity, makes it difficult to interpret unambiguously the currently available body of facts on their functions. Deciphering the molecular genetic mechanisms of mitochondrial structural disorders and dysfunction may become a basis for development of effective diagnostic methods and targeted therapy for male infertility.

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Sperm redox biology challenges the role of antioxidants as a treatment for male factor infertility

Cited by 10 publications

References 88 publications

Sperm as a Carrier of Genome Instability in Relation to Paternal Lifestyle and Nutritional Conditions

Sperm as a Carrier of Genome Instability in Relation to Paternal Lifestyle and Nutritional Conditions

The effect of green coffee and/or endurance exercise on sperm function in pre‐diabetic mice

The role of sperm mitochondria in the occurrence and development of male infertility

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