Sirt1 sustains female fertility by slowing age‐related decline in oocyte quality required for post‐fertilization embryo development

Iljas, Juvita D.; Wei, Zhe; Homer, Hayden

doi:10.1111/acel.13204

Cited by 56 publications

(44 citation statements)

References 46 publications

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“…40,46 In line with this, we showed that deletion from oocytes of the sirtuin, SIRT1 (a major regulator of mitochondrial function), results in increased oxidative stress that compromises embryonic development leading to early-onset infertility in female mice. 47 There is therefore intense interest in the use of antioxidants for improving oocyte quality. One example is coenzyme Q10 (CoQ10), a well-known component of the mitochondrial electron transport chain.…”

Section: Prospects and Challenges For Diagnosing And Improving Poor Omentioning

confidence: 99%

The Role of Oocyte Quality in Explaining “Unexplained” Infertility

Homer

2020

Semin Reprod Med

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Infertility is described as unexplained when pregnancy does not occur despite ovulation, patent Fallopian tubes, and normal semen parameters. Oocyte developmental competence (or quality) is rate-limiting for pregnancy success as oocytes provide virtually all the cellular building blocks including mitochondria required during embryogenesis. However, available tests estimate oocyte numbers (anti-Müllerian hormone, follicle-stimulating hormone and antral follicle count) and ovulation (luteal phase serum progesterone) but not the third, and most pivotal, oocyte-specific parameter, quality. Severe depletion of the follicular reserve manifests as premature ovarian insufficiency and is an obvious cause of anovulation with overt symptoms and clear diagnostic criteria. In contrast, there are no biomarkers of poor oocyte quality other than through in vitro fertilization when readouts of oocyte quality such as preimplantation embryo development can be assessed. The most common cause of poor oocyte quality is natural aging, which is strongly tied to reduced oocyte mitochondrial efficiency and increased oxidative stress. In younger women, quality may also be impaired due to accelerated aging or sporadic genetic mutations which cause severe defects during oocyte and embryo development. Thus, poor oocyte quality often provides an explanation for infertility, but because it cannot be measured using conventional tests, many cases of infertility are often incorrectly labeled “unexplained.” Since female age remains the best predictor of oocyte quality, age over 37 years should be considered an independent diagnostic criterion.

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Section: Prospects and Challenges For Diagnosing And Improving Poor Omentioning

confidence: 99%

The Role of Oocyte Quality in Explaining “Unexplained” Infertility

Homer

2020

Semin Reprod Med

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“…However, Iljas et al found that SIRT1‐knockout mice do not exhibit any such impact on the oocytes, rather it affects the early cleavage divisions post‐fertilisation secondary to OS within the embryo. Furthermore, they demonstrated that despite lack of mitochondria in the aged SIRT1‐deficient oocytes, the cause of infertility is the same; post‐fertilisation embryo cleavage defect 41 . This suggest that in aged oocyte the reduced maternal SIRT1 becomes critical for the embryonic development as the OS developed during this phase lacks the compensatory mechanism offered by SIRT1 (in young oocytes).…”

Section: Discussionmentioning

confidence: 99%

Suggested role of silent information regulator 1 (SIRT1) gene in female infertility: A cross‐sectional study in Pakistan

Alam

Rehman

Fatima

et al. 2021

Int J Clinical Practice

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Aim & Objective Silent information regulator 1 (SIRT1) gene stimulates the expression of antioxidants and repairs damaged cells. It affects the mitochondrial activity within the oocytes to overcome the oxidant stress. We aimed to assess an association of SIRT1 polymorphism (Tag SNPs rs10509291 and rs12778366) with fertility, and assess serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), oestradiol, progesterone, manganese superoxide (MnSOD) and SIRT1. Material and Methods In this cross‐sectional study, 207 fertile and 135 infertile subjects between the ages of 18‐45 years were recruited. Polymerase chain reaction (PCR) was performed; products were electrophoresed in a 2% agarose gel. Descriptive analysis of continuous variables was expressed as mean ± standard deviation. Mann‐Whitney test was performed for comparison of groups, P value <.001 was considered significant. Single Nucleotide Polymorphism (SNP) data were analysed by applying chi‐squared statistics. Results All subjects were age matched (P = .896). SIRT1 levels were significantly lower in infertile females when compared with fertile subjects (P < .001). AA (rs10509291) and CC (rs12778366) variant frequency was higher in the infertile than fertile subjects (P < .01). Similarly, the frequency of A allele (rs10509291) and C allele (rs12778366) was higher in infertile subjects (P < .001). Infertile females (29%) showed existence of SNP rs10509291 while 49% demonstrated genetic variation of rs12778366. MnSOD and SIRT1 levels were found to be lower in these subjects. Conclusion The presence of SIRT1 genetic variants (rs10509291 and rs12778366) apparently disturbs the expression of SIRT1 deteriorating mitochondrial antioxidant function within the oocytes, instigating oxidative stress within. Their probable effect on modulating oocyte maturation may be the cause of infertility in females.

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“…Recent evidence suggests that SIRT1 plays a role in oocyte function in older ages (Iljas et al, 2020) embryogenesis. Antral follicles differ substantially from primordial follicles, as is evident from the wave-like pattern of DNA methylation.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic clock and methylation study of oocytes from a bovine model of reproductive aging

et al. 2021

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The mammalian female reproductive axis is the first to fail in aging; however, the molecular mechanisms underpinning this failure are largely unknown, particularly in oocytes (Chamani & Keefe, 2019;Garg & Sinclair, 2015;Homer, 2020). Fertility in women begins to decline significantly by their mid-30 s and pregnancies in women of advanced age lead to higher rates of miscarriage and/or aneuploid offspring (Baired et al., 2005). Despite these risks, women and couples often postpone pregnancy to a more convenient time which has led to a decline in birthrate among most industrialized societies (Homer, 2020;Navot et al., 1991). This decline in fertility can be explained by the age-related decline in oocyte quality which manifests itself by chromosomal abnormalities, spindle defects, mi-

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Sirt1 sustains female fertility by slowing age‐related decline in oocyte quality required for post‐fertilization embryo development

Cited by 56 publications

References 46 publications

The Role of Oocyte Quality in Explaining “Unexplained” Infertility

The Role of Oocyte Quality in Explaining “Unexplained” Infertility

Suggested role of silent information regulator 1 (SIRT1) gene in female infertility: A cross‐sectional study in Pakistan

Epigenetic clock and methylation study of oocytes from a bovine model of reproductive aging

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