Impact of Maternal Age on Oocyte and Embryo Competence

Cimadomo, Danilo; Fabozzi, Gemma; Vaiarelli, Alberto; Ubaldi, Nicolò; Ubaldi, Filippo Maria; Rienzi, Laura

doi:10.3389/fendo.2018.00327

Cited by 321 publications

(241 citation statements)

References 109 publications

(121 reference statements)

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“…Aging is a major detrimental factor for achieving pregnancy due to ovarian aging leading to mitochondrial dysfunction, telomere shortening, cohesion dysfunctions, and spindle instability. Both genetic and environmental factors contribute to aging damage, but the major mechanism underlying ovarian deterioration is chronic damage by reactive oxygen species (ROS) . Reactive oxygen species can damage mitochondria DNA, promoting mutations, and induce telomere shortening and cellular senescence .…”

Section: Impact On Ovary For Pregnancymentioning

confidence: 99%

“…Both genetic and environmental factors contribute to aging damage, but the major mechanism underlying ovarian deterioration is chronic damage by reactive oxygen species (ROS). 11,[14][15][16] Reactive oxygen species can damage mitochondria DNA, promoting mutations, and induce telomere shortening and cellular senescence. 17 Resveratrol is a natural activator of sirtuin, the NAD + -dependent deacetylase.…”

Section: Agingmentioning

confidence: 99%

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Preconception resveratrol intake against infertility: Friend or foe?

Ochiai

Kuroda

2019

Reprod Medicine & Biology

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Background Resveratrol is an antiaging, antioxidant, anti‐inflammatory, and insulin‐sensitizing natural polyphenolic compound. Growing evidence indicates that resveratrol has potential therapeutic effects in infertile women with diminished ovarian function, polycystic ovary syndrome (PCOS), or endometriosis. However, only one clinical trial in women undergoing in vitro fertilization (IVF) cycles using resveratrol has ever been reported. This review focuses on the potential therapeutic effects of resveratrol on pregnancy and on its advantages and disadvantages in pregnancy outcomes during infertility treatment. Methods We performed a literature review to describe the known impacts of resveratrol on the ovary and endometrium. Results Resveratrol upregulates sirtuin (SIRT)1 expression in ovaries, which is associated with protection against oxidative stress. It leads to the activation of telomerase activity and mitochondrial function, improving ovarian function. In the endometrium, resveratrol downregulates the CRABP2‐RAR pathway leading to suppressing decidual and senescent changes of endometrial cells, which is essential for embryo implantation and placentation. Moreover, resveratrol may also induce deacetylation of important decidual‐related genes. Conclusions Resveratrol has potential therapeutic effects for improving ovarian function; however, it also has anti‐deciduogenic actions in uterine endometrium. In addition, its teratogenicity has not yet been ruled out; thus, resveratrol should be avoided during the luteal phase and pregnancy.

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Section: Impact On Ovary For Pregnancymentioning

confidence: 99%

Section: Agingmentioning

confidence: 99%

Preconception resveratrol intake against infertility: Friend or foe?

Ochiai

Kuroda

2019

Reprod Medicine & Biology

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Section: Introductionmentioning

confidence: 99%

Intergenerational effects on offspring telomere length: interactions among maternal age, stress exposure and offspring sex

et al. 2019

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Offspring produced by older parents often have reduced longevity, termed the Lansing effect. Because adults usually have similar-aged mates, it is difficult to separate effects of maternal and paternal age, and environmental circumstances are also likely to influence offspring outcomes. The mechanisms underlying the Lansing effect are poorly understood. Variation in telomere length and loss, particularly in early life, is linked to longevity in many vertebrates, and therefore changes in offspring telomere dynamics could be very important in this context. We examined the effect of maternal age and environment on offspring telomere length in zebra finches. We kept mothers under either control (ad libitum food) or more challenging (unpredictable food) circumstances and experimentally minimized paternal age and mate choice effects. Irrespective of the maternal environment, there was a substantial negative effect of maternal age on offspring telomere length, evident in longitudinal and cross-sectional comparisons (average of 39% shorter). Furthermore, in young mothers, sons reared by challenged mothers had significantly shorter telomere lengths than sons reared by control mothers. This effect disappeared when the mothers were old, and was absent in daughters. These findings highlight the importance of telomere dynamics as inter-generational mediators of the evolutionary processes determining optimal age-specific reproductive effort and sex allocation.

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“…Advancing maternal age is associated with decreased quality of oocytes (reviewed in [54]), from altered epigenetic profiles [55] and mitochondrial DNA deletions [56]. Aged oocytes also display altered microtubule spindle alignment [57] and weakened centromere cohesion [58] resulting in increased risk of aneuploidy.…”

Section: Discussionmentioning

confidence: 99%

Whole genome analysis reveals aneuploidies in early pregnancy loss in the horse

Shilton

Kahler

Davis

et al. 2020

Preprint

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Chromosome abnormalities are well documented in human spontaneous abortion studies, yet rarely reported in domesticated animals. Rodent models have previously been used to study the effects of maternal ageing on oocyte quality and ultimately aneuploidy, however the differing endocrine profiles, oocyte characteristics and the polytocous nature of rodents are limitations for translation into human medicine. Early Pregnancy Loss (EPL) occurs in 5-10% of confirmed equine pregnancies and has no diagnosis in over 80% of cases. Aneuploidy has never been described in equine pregnancy loss, thus the objectives of this study were to quantify the frequency and characteristics of aneuploidy associated with equine EPL. EPL conceptuses were submitted from clinical cases of spontaneous pregnancy loss (14-65 days of gestation) between 2013 and 2018. Age matched control conceptuses were obtained from terminated clinically normal pregnancies (CNP). Aneuploidy was detected in 12/55 EPLs (21.8%), 0/10 CNP, 0/5 healthy term chorioallantois, and 0/5 healthy adult mares via genotyping. Whole genome sequencing (30X) and ddPCR validated results. Aneuploidies involved 10/32 equine chromosomes, consisting of nine trisomies and three monosomies. Autosomal aneuploidies were detected in both placental and fetal compartments in all samples tested. Aneuploid types (7/9) were mostly unique to EPL, supporting their embryonic/fetal lethality. Presenting the first evidence of aneuploidies in failed equine pregnancies not only provides the initial step in identifying genetic causes for these early losses, but also offers the horse as a new model for studying naturally occurring aneuploidy. We also demonstrate that SNP arrays provide a simple, cost effective way to screen aneuploidies across a large population.Author SummaryThe first 8 weeks of pregnancy is a critical time in both humans and horses, as the majority of pregnancy losses occur during this period. Despite such high prevalence, many cases do not have a known cause. Abnormal chromosome number (aneuploidy) is the most common finding in human pregnancy loss studies, but to date no equivalent study has been performed in domesticated animals, including the horse. We studied the genetics of naturally occurring pregnancy losses from Thoroughbred horses and found a similar level of aneuploidy to that observed in women. As humans and horses share similarities in their reproductive biology (ageing eggs, increased pregnancy loss in older mothers, similar key hormones), we suggest that by comparing the genetics of these two species, greater advances in identifying causes of aneuploidy pregnancy can be reached. Thoroughbred horses also tend to be more inbred than humans, facilitating the identification of mutations that increase the chance of aneuploidy, and this knowledge could potentially be applied in human medicine, as well as in species conservation.

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Impact of Maternal Age on Oocyte and Embryo Competence

Cited by 321 publications

References 109 publications

Preconception resveratrol intake against infertility: Friend or foe?

Preconception resveratrol intake against infertility: Friend or foe?

Intergenerational effects on offspring telomere length: interactions among maternal age, stress exposure and offspring sex

Whole genome analysis reveals aneuploidies in early pregnancy loss in the horse

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