Individuals age reproductively, partly due to damage to germ-line DNA from environmental insults and errors in DNA replication, but each new generation starts out young. Most problematic germ-line mutations are culled via cell death, nonfunctional gametes, and embryonic death. In addition, degradation at the species level likely is minimised by convergent evolution; no strong evidence was found for rejuvenation of DNA.
Reproduction, Fertility and Development
Volume 27 Number 6 2015
Comparative Aspects of Reproductive Aging between the Mare and Woman
RD14390Not just a number: effect of age on fertility, pregnancy and offspring vigour in thoroughbred brood-mares
In thoroughbreds, the influence of age on a mare’s reproductive efficiency and her offspring’s vigour cannot be understated. Age-related changes can contribute to a reduction in fertility and increase the risk of progeny morbidity and mortality. These findings can adversely affect reproductive management of the mare, as well as future commercial value and racing performance of both the mare and her offspring.
Early embryo development in mammals is heavily dependent on the stored maternal factors in oocytes. Herein we summarise the maternal factors affecting early embryo development and functions of maternal-effect genes identified in mammals. Perturbations of maternal control, some of which are associated with ovarian aging, result in decreased oocyte quality.
RD14452Effects of age on follicular fluid exosomal microRNAs and granulosa cell transforming growth factor-β signalling during follicle development in the mare
Age-related decline in fertility is a consequence of low oocyte number and low oocyte competence (the ability of a fertilised oocyte to develop into an embryo), ultimately resulting in pregnancy failure. Regulation of transforming growth factor (TGF)-β signalling members by small non-coding microRNAs (miRNAs) could explain the age-related effects on oocyte maturation and quality. In the present study we identified altered levels of miRNAs present in follicular fluid exosomes from young and old mares that are predicted to regulate members of the TGF-β signalling pathway in surrounding granulosa cells; this could ultimately help explain age-related decline in fertility.
RD14467Age-associated changes in granulosa cell transcript abundance in equine preovulatory follicles
Increased maternal age is associated with reduced pregnancy rates; however, age-related disruptions to normal follicular function remains unknown. The current study determined age-related disruptions to gene regulation in the follicles for many normal processes involved in follicular maturation. We have identified numerous candidate genes that could be used as potential markers for follicle and oocyte viability in aged animals.
There is compelling evidence that oocytes from mares >18 years of age have a high incidence of inherent defects that result in early embryonic loss. We compared the gene expression profiles of individual oocytes and cumulus cells from young and aged mares. Three genes (IF3, HSF5 and YBX2) were more abundantly expressed in young mare oocytes and three genes (ARL6IP, BAX and HYOU1) were more abundantly expressed in aged mare cumulus cells. These results confirm there are age-related differences in gene expression in equine cumulus–oocyte complexes, that may be associated with the lower quality and decreased developmental competence of oocytes from aged mares.
RD14472Effects of aging on gene expression and mitochondrial DNA in the equine oocyte and follicle cells
Maternal aging is related to reduced fertility in various species, including the mare. We compared gene expression in follicle cells and oocytes from Young and Old mares after an ovulation-induction signal. Differences were observed in the timing and amount of expression for key regulatory genes between Young and Old mares, suggesting age-associated changes in follicles and oocytes that could impact fertility.
RD14493Centrosome and microtubule functions and dysfunctions in meiosis: implications for age-related infertility and developmental disorders
Chromosomal abnormalities, increased spontaneous abortion and reduced fertility are associated with maternal aging which has resulted in increased demands for assisted reproductive technologies (ARTs) to increase the chances for the birth of a healthy baby. The aim of this study was to review the mechanisms leading to chromosomal abnormalities in aging oocytes with focus on centrosome and microtubule dynamics in the meiotic MII spindle that are affected by maternal aging but can be treated with specific chemicals to delay or reverse the aging effects. Such treatments may find applications for ART procedures in in vitro fertilisation (IVF) clinics to increase the success rates for the birth of healthy babies.
RD14468Cytoskeletal alterations associated with donor age and culture interval for equine oocytes and potential zygotes that failed to cleave after intracytoplasmic sperm injection
Sperm-injected equine oocytes that failed to cleave after ICSI were analysed by confocal microscopy to determine the stage of arrest with emphasis on the cytoskeletal components, actin and tubulin. Alterations associated with cell aging and aging of the oocyte donor were observed, suggesting oocytes from younger mares aged as anticipated with potential attempt at activation, while oocytes from older donors had alterations in actin configurations. Cytoskeletal organisation and zygote development is impacted by maternal and cell aging and is important to understand in clinical applications.
RD14450Maternal age and in vitro culture affect mitochondrial number and function in equine oocytes and embryos
Advancing maternal age and in vitro embryo production (IVP) both predispose to embryonic death. We generated support for the hypothesis that reduced mitochondrial number contributes to compromised embryo quality in these scenarios, by demonstrating reduced mitochondrial DNA (mtDNA) copy numbers in Day 7 embryos from mares older than 12 years, and reduced expression of genes involved in mtDNA replication in oocytes following culture in vitro.
This review discusses the link between stem cells, fertility and aging. The work listed provides insight into an emerging field in female fertility, namely, germline stem cells or OSCs and postnatal oogenesis. Given that oocyte numbers decline with age, it is possible that menopause is not a result of exhaustion of the ovarian reserve, rather a result of aging of OSCs.
RD14474Antioxidant supplementation during in vitro culture improves mitochondrial function and development of embryos from aged female mice
Maternal aging results in reduced blastocyst quality, thought to be due to mitochondrial dysfunction. The present study shows that culture of embryos from aged mice in the presence of a cocktail of antioxidants is beneficial to mitochondrial function and embryo development. Our results highlight the need for a targeted modulation of the redox state to support requirements of embryos originating from reproductively aged females.