To what extent can oocytes repair sperm DNA fragmentation?

Cozzubbo, T.; Neri, Q.V.; Rosenwaks, Zev; Palermo, G.D.

doi:10.1016/j.fertnstert.2014.07.208

Cited by 13 publications

(9 citation statements)

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“…In the case of fertilisation, sperm DNA fragmentation can to some extent be repaired by the oocyte. However, with advancing age, the oocyte quality is deteriorating, together with its repair capacity ( Cozzubbo et al ., 2014 ). This supports the hypothesis that the impact of paternal age on miscarriage, mediated by an increased DFI, is more present in interaction with higher maternal age.…”

Section: Discussionmentioning

confidence: 99%

Advanced paternal age is associated with an increased risk of spontaneous miscarriage: a systematic review and meta-analysis

Fossé

Hoorn

Lith

et al. 2020

Human Reproduction Update

173

103

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BACKGROUND Although spontaneous miscarriage is the most common complication of human pregnancy, potential contributing factors are not fully understood. Advanced maternal age has long been recognised as a major risk factor for miscarriage, being strongly related with fetal chromosomal abnormalities. The relation between paternal age and the risk of miscarriage is less evident, yet it is biologically plausible that an increasing number of genetic and epigenetic sperm abnormalities in older males may contribute to miscarriage. Previous meta-analyses showed associations between advanced paternal age and a broad spectrum of perinatal and paediatric outcomes. This is the first systematic review and meta-analysis on paternal age and spontaneous miscarriage. OBJECTIVE AND RATIONALE The aim of this systematic review and meta-analysis is to evaluate the effect of paternal age on the risk of spontaneous miscarriage. SEARCH METHODS PubMed, Embase and Cochrane databases were searched to identify relevant studies up to August 2019. The following free text and MeSH terms were used: paternal age, father’s age, male age, husband’s age, spontaneous abortion, spontaneous miscarriage, abortion, miscarriage, pregnancy loss, fetal loss and fetal death. PRISMA guidelines for systematic reviews and meta-analysis were followed. Original research articles in English language addressing the relation between paternal age and spontaneous miscarriage were included. Exclusion criteria were studies that solely focused on pregnancy outcomes following artificial reproductive technology (ART) and studies that did not adjust their effect estimates for at least maternal age. Risk of bias was qualitatively described for three domains: bias due to confounding, information bias and selection bias. OUTCOMES The search resulted in 975 original articles. Ten studies met the inclusion criteria and were included in the qualitative synthesis. Nine of these studies were included in the quantitative synthesis (meta-analysis). Advanced paternal age was found to be associated with an increased risk of miscarriage. Pooled risk estimates for miscarriage for age categories 30–34, 35–39, 40–44 and ≥45 years of age were 1.04 (95% CI 0.90, 1.21), 1.15 (0.92, 1.43), 1.23 (1.06, 1.43) and 1.43 (1.13, 1.81) respectively (reference category 25–29 years). A second meta-analysis was performed for the subgroup of studies investigating first trimester miscarriage. This showed similar pooled risk estimates for the first three age categories and a slightly higher pooled risk estimate for age category ≥45 years (1.74; 95% CI 1.26, 2.41). WIDER IMPLICATIONS Over the last decades, childbearing at later ages has become more common. It is known that frequencies of adverse reproductive outcomes, including spontaneous miscarriage, are higher in women with advanced age. We show that advanced paternal age is also associated with an increased risk of spontaneous miscarriage. Although the paternal age effect is less pronounced than that observed with advanced maternal age and residual confounding by maternal age cannot be excluded, it may have implications for preconception counselling of couples comprising an older aged male.

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Section: Discussionmentioning

confidence: 99%

Advanced paternal age is associated with an increased risk of spontaneous miscarriage: a systematic review and meta-analysis

Fossé

Hoorn

Lith

et al. 2020

Human Reproduction Update

173

103

View full text Add to dashboard Cite

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“…Fertilization with spermatozoa bearing a high level of oxidized residues that will potentially overwhelm the oocyte repair capacity is one of these situations. On the female side, oocytes coming from aging women or oocytes that have been stressed following for example hormonal stimulation during ART, chemo or radiation therapies or cryoconservation, all situations that are known to reduce egg quality, represent other classical cases that could lead to incomplete sperm nuclear repair, potentially leading to adverse developmental consequences including an increased mutational load in the next generation [ 49 , 50 , 51 , 52 , 53 , 54 ]. Any weakness in the spermatozoa’s ability to create abasic sites via its OGG1 activity when facing excessive oxidation of guanine residues, in addition to any weakness in the oocyte ability to complete the BER pathway after fertilization, will therefore promote a classical Hoogsteen-type base pair mismatch, which will lead to de novo G to T transversion mutations that will be carried on to any cell of the developing embryo [ 16 , 55 ].…”

Section: Undisputable Consequences Of Sperm Dna Oxidationmentioning

confidence: 99%

Oxidation of Sperm DNA and Male Infertility

et al. 2021

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One important reason for male infertility is oxidative stress and its destructive effects on sperm structures and functions. The particular composition of the sperm membrane, rich in polyunsaturated fatty acids, and the easy access of sperm DNA to oxidative damage due to sperm cell specific cytologic and metabolic features (no cytoplasm left and cells unable to mount stress responses) make it the cell type in metazoans most susceptible to oxidative damage. In particular, oxidative damage to the spermatozoa genome is an important issue and a cause of male infertility, usually associated with single- or double-strand paternal DNA breaks. Various methods of detecting sperm DNA fragmentation have become important diagnostic tools in the prognosis of male infertility and such assays are available in research laboratories and andrology clinics. However, to date, there is not a clear consensus in the community as to their respective prognostic value. Nevertheless, it is important to understand that the effects of oxidative stress on the sperm genome go well beyond DNA fragmentation alone. Oxidation of paternal DNA bases, particularly guanine and adenosine residues, the most sensitive residues to oxidative alteration, is the starting point for DNA damage in spermatozoa but is also a danger for the integrity of the embryo genetic material independently of sperm DNA fragmentation. Due to the lack of a spermatozoa DNA repair system and, if the egg is unable to correct the sperm oxidized bases, the risk of de novo mutation transmission to the embryo exists. These will be carried on to every cell of the future individual and its progeny. Thus, in addition to affecting the viability of the pregnancy itself, oxidation of the DNA bases in sperm could be associated with the development of conditions in young and future adults. Despite these important issues, sperm DNA base oxidation has not attracted much interest among clinicians due to the lack of simple, reliable, rapid and consensual methods of assessing this type of damage to the paternal genome. In addition to these technical issues, another reason explaining why the measurement of sperm DNA oxidation is not included in male fertility is likely to be due to the lack of strong evidence for its role in pregnancy outcome. It is, however, becoming clear that the assessment of DNA base oxidation could improve the efficiency of assisted reproductive technologies and provide important information on embryonic developmental failures and pathologies encountered in the offspring. The objective of this work is to review relevant research that has been carried out in the field of sperm DNA base oxidation and its associated genetic and epigenetic consequences.

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“…Cozzubbo et al y col., (2014) encontraron que los oocitos de mujeres jóvenes tienen la capacidad de reparar el ADN espermático hasta en un 40%, mientras que los oocitos de mujeres mayores son más sensibles. 10 La reparación de ese daño, depende de la edad de la mujer, el ambiente ovárico y el tipo de infertilidad, las cuales son variables que no afectan usando oocitos donados. 28 Así mismo, Seli y col., (2004), encontraron que el efecto mitigador del oocito sobre el daño se ve alterado con el aumento de la edad, ya que hallaron una relación entre el daño del ADN paterno y una baja formación de blastocistos en donde la edad de la mujer era de aproximadamente 35 años, 29 lo que concuerda con este estudio, la media de la edad de las mujeres que usaron sus propios oocitos fue de 35 años.…”

Section: Discussionunclassified

“…Después de la escisión de los grupos acetato por las esterasas intracelulares, el DCFH oxida selectivamente por las ERO y ERN hasta 2', 7'diclorofluoresceína (DCF) el cual fluoresce en verde. 10 El IP se utilizó para excluir las células necróticas/muertas. La suspensión de células se incubó protegida de la luz (30 min, a 25°C), se lavó tres veces con PBS (180 g, 5 min) y el botón fue resuspendido en PBS antes de ser analizado por citometría de flujo.…”

Section: Producción Intracelular De Especies Reactivas Del Oxígeno (Eunclassified

Los parámetros espermáticos funcionales como factor pronóstico en ICSI: Experiencia de la ciudad de Medellín

Calderón-Mendoza¹,

López²,

Giraldo³

et al. 2019

Urol Colomb

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Introducción La infertilidad por factor masculino afecta al 30% de las parejas infértiles y la evaluación seminal es crítica en las determinaciones que conllevan a un posible tratamiento con el fin de tener un resultado exitoso. Objetivo El objetivo de este estudio fue evaluar la relación que existe entre los parámetros seminales convencionales y funcionales, con las tasas de fecundación, desarrollo embrionario y embarazo obtenidas después de inyección intracitoplasmática de espermatozoides (ICSI). Métodos 36 muestras seminales de parejas que se sometieron a ICSI (18 usando oocitos propios y 18 de donante), fueron evaluadas de manera convencional, posteriormente se seleccionaron los espermatozoides, se realizó ICSI y una alícuota se utilizó para cuantificar las siguientes pruebas funcionales: potencial de membrana mitocondrial, integridad de la membrana, detección de especies reactivas de oxígeno e índice de fragmentación del ADN. Resultados No se encontraron diferencias significativas en cuanto a los parámetros convencionales y funcionales en los dos grupos, como tampoco se encontró una relación significativa entre los parámetros evaluados y los resultados de ICSI. Sólo se observó que la tasa de embarazo fue mayor en el grupo de oocitos donados (p < 0,0001). Conclusiones Los datos obtenidos en este estudio sugieren que no existe correlación entre los parámetros evaluados y los resultados de ICSI. Eso se debe probablemente, a que la selección de los espermatozoides tanto por gradientes de densidad como la posterior selección durante el procedimiento del ICSI, tiene un bajo poder predictivo sumado a la capacidad que tiene el oocito de reparar los daños presentes en el espermatozoide.

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To what extent can oocytes repair sperm DNA fragmentation?

Cited by 13 publications

References 0 publications

Advanced paternal age is associated with an increased risk of spontaneous miscarriage: a systematic review and meta-analysis

Advanced paternal age is associated with an increased risk of spontaneous miscarriage: a systematic review and meta-analysis

Oxidation of Sperm DNA and Male Infertility

Los parámetros espermáticos funcionales como factor pronóstico en ICSI: Experiencia de la ciudad de Medellín

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