Ovum quality

Ovum quality is the measure of the ability of an oocyte (the female gamete) to achieve successful fertilisation. The quality is determined by the maturity of the oocyte and the cells that it comprises, which are susceptible to various factors which impact quality and thus reproductive success.[1] This is of significance as an embryo's development is more heavily reliant on the oocyte in comparison to the sperm.[1]

Factors

Age

Advanced maternal age represents a significant consideration for ovum health, and is currently regarded as the largest risk factor underlying instances of aneuploidy in human populations.[2] The mechanisms by which ovum health degenerates with age are incompletely understood. Extended meiotic arrest, a decline in mitochondrial function, and oxidative stress are key factors associated with ageing that are damaging to oocyte quality, identified in studies utilising both human and animal oocytes.[3]

Meiotic arrest and loss of cohesion

The formation of human gametes involves two separation events, known distinctly as Meiosis I, in which paired homologous chromosomes are separated, and Meiosis II, in which sister chromatids are divided. Meiosis I is a slightly elongated process, during which homologous chromosomes align, pair, and recombine.[3]

While male gametes (sperm) are continuously produced throughout life, the female ovarian reserve is fully formed during early development. Oocytes (but not spermatocytes) then undergo a prolonged arrest at the end of diplotene, until meiosis resumes at the beginning of the menstrual cycle. It is during this prolonged arrest that age-dependent changes or deterioration may occur.[4]

During the oocyte's prolonged arrest, chromosomes exist as bivalents. This means that homologous chromosomes have paired, and are being held together by chiasmata (the physical crossovers between chromosome arms). The cohesin complex, a ring like structure associated with sister chromatids, helps to hold them in close proximity, therefore generating sister chromatid cohesion. This cohesion is later broken by the enzyme separase, allowing the chiasmata to be broken and homologous chromosomes to segregate in a normal way.[5]  Age-related degeneration of the inhibitors and regulators of separase, may lead to inappropriate and premature cohesin degradation before anaphase. As a result, homologous chromosomes may align independently on the meiotic spindle, risking aneuploidy that represents a key mechanism of reduced reproductive success.[5]

Mitochondrial changes

As the most mitochondria-dense cells in the body, ova depend upon these organelles for early embryonic development, proliferation and their competence for fertilisation. Therefore, age-related changes to mitochondrial function naturally represent a significant influence on ovum quality and female fertility.[6]

Specific changes that occur with age include a reduction in quantity of mitochondrial DNA, as well as an increase in mitochondrial DNA mutations.[7] Animal studies have demonstrated these genetic abnormalities, in addition to physical changes in the mitochondria themselves and reduced ATP production.[8] Further investigation is required to establish definitive evidence for decreasing developmental potential as a result of aging mitochondria,[7] however the accumulation of mitochondrial abnormalities over time in the female ovum has been established, and appears linked in some way to declining ova health.[9]

Obesity

Studies show that obesity affects the quality of the ovum. It is a disease which decreases the fertility of the female.[10] This is mainly due to causing a disturbance to maternal hormonal levels.[10] It is also possible for the uterus to have different levels of receptivity with regards to oocyte attachment, as a result of a disturbance to the function of the endometrium.[10] Furthermore, ingesting higher levels of carbohydrates and increased levels of glucose in the diet has been related to a higher chance of infertility because of the ovary failing to release oocytes at ovulation.[10] Obesity also has been linked to early miscarriages, deaths of the foetus, new-born or deaths where the baby is born dead and there is an increased chance of the babies having birth defects.[10]

In the IVF procedure a hormone called gonadotropin (GnRH) is given to the female to stimulate the ovaries to release oocytes.[10] In obese patients, their obesity negatively affects the ovaries responsiveness to this hormonal stimulant leading to doctors having to administrate an increased dose of the hormone and the duration of stimulation is increased.[10] Less mature oocytes are harvested. Moreover, obesity leads to decreased pregnancy rates after IVF and a smaller chance of the oocyte implanting to the uterine wall. They also have an increased chance of the cycle being cancelled.[10]

Damage from lipotoxicity

An overload of fatty acids in the body due to increased ingestion can lead to lipotoxicity.[11] These extra fatty acids are not stored by the body and instead they circulate and damage the surrounding tissue. Levels of excess Fatty acids are higher in obese women.[11] The fatty acid will damage other cells, except for the adipocytes, by producing more reactive oxygen species. This causes the cell to self-destruct (apoptosis).[11]

Stress

Psychological stress

Psychological stress can contribute both directly and indirectly to decreased oocyte quality. Increased stress leads to an increased production and release of cortisol, a stress hormone, which directly inhibits the biosynthesis of estradiol in the ovary.[12] A decrease in estradiol as well as oxidative stress leads to apoptosis of the granulosa cells off the oocyte which deteriorates oocyte quality.[12]

References

  1. 1 2 Coticchio, Giovanni; Sereni, Elena; Serrao, Lucia; Mazzone, Silvia; Iadarola, Immacolata; Borini, Andrea (December 2004). "What criteria for the definition of oocyte quality?". Annals of the New York Academy of Sciences. 1034 (1): 132–144. Bibcode:2004NYASA1034..132C. doi:10.1196/annals.1335.016. ISSN 0077-8923. PMID 15731306.
  2. ↑ Herbert, Mary; Kalleas, Dimitrios; Cooney, Daniel; Lamb, Mahdi; Lister, Lisa (2015-04-01). "Meiosis and maternal aging: insights from aneuploid oocytes and trisomy births". Cold Spring Harbor Perspectives in Biology. 7 (4): a017970. doi:10.1101/cshperspect.a017970. ISSN 1943-0264. PMC 4382745. PMID 25833844.
  3. 1 2 MacLennan, Marie; Crichton, James H.; Playfoot, Christopher J.; Adams, Ian R. (September 2015). "Oocyte development, meiosis and aneuploidy". Seminars in Cell & Developmental Biology. 45: 68–76. doi:10.1016/j.semcdb.2015.10.005. ISSN 1096-3634. PMC 4828587. PMID 26454098.
  4. ↑ Jones, Keith T.; Lane, Simon I. R. (September 2013). "Molecular causes of aneuploidy in mammalian eggs". Development. 140 (18): 3719–3730. doi:10.1242/dev.090589. ISSN 1477-9129. PMID 23981655.
  5. 1 2 Cheng, Jin-Mei; Liu, Yi-Xun (2017-07-22). "Age-Related Loss of Cohesion: Causes and Effects". International Journal of Molecular Sciences. 18 (7): 1578. doi:10.3390/ijms18071578. ISSN 1422-0067. PMC 5536066. PMID 28737671.
  6. ↑ May-Panloup, Pascale; Boucret, Lisa; Chao de la Barca, Juan-Manuel; Desquiret-Dumas, Valérie; Ferré-L'Hotellier, Véronique; Morinière, Catherine; Descamps, Philippe; Procaccio, Vincent; Reynier, Pascal (November 2016). "Ovarian ageing: the role of mitochondria in oocytes and follicles". Human Reproduction Update. 22 (6): 725–743. doi:10.1093/humupd/dmw028. ISSN 1460-2369. PMID 27562289.
  7. 1 2 Babayev, Elnur; Seli, Emre (June 2015). "Oocyte mitochondrial function and reproduction". Current Opinion in Obstetrics & Gynecology. 27 (3): 175–181. doi:10.1097/GCO.0000000000000164. ISSN 1473-656X. PMC 4590773. PMID 25719756.
  8. ↑ Simsek-Duran, Fatma; Li, Fang; Ford, Wentia; Swanson, R. James; Jones, Howard W.; Castora, Frank J. (2013). "Age-associated metabolic and morphologic changes in mitochondria of individual mouse and hamster oocytes". PLOS ONE. 8 (5): e64955. Bibcode:2013PLoSO...864955S. doi:10.1371/journal.pone.0064955. ISSN 1932-6203. PMC 3669215. PMID 23741435.
  9. ↑ Rebolledo-Jaramillo, Boris; Su, Marcia Shu-Wei; Stoler, Nicholas; McElhoe, Jennifer A.; Dickins, Benjamin; Blankenberg, Daniel; Korneliussen, Thorfinn S.; Chiaromonte, Francesca; Nielsen, Rasmus; Holland, Mitchell M.; Paul, Ian M. (2014-10-28). "Maternal age effect and severe germ-line bottleneck in the inheritance of human mitochondrial DNA". Proceedings of the National Academy of Sciences of the United States of America. 111 (43): 15474–15479. Bibcode:2014PNAS..11115474R. doi:10.1073/pnas.1409328111. ISSN 1091-6490. PMC 4217420. PMID 25313049.
  10. 1 2 3 4 5 6 7 8 Luke, Barbara (April 2017). "Adverse effects of female obesity and interaction with race on reproductive potential". Fertility and Sterility. 107 (4): 868–877. doi:10.1016/j.fertnstert.2017.02.114. ISSN 1556-5653. PMID 28366413.
  11. 1 2 3 Broughton, Darcy E.; Moley, Kelle H. (April 2017). "Obesity and female infertility: potential mediators of obesity's impact". Fertility and Sterility. 107 (4): 840–847. doi:10.1016/j.fertnstert.2017.01.017. ISSN 1556-5653. PMID 28292619.
  12. 1 2 Prasad, Shilpa; Tiwari, Meenakshi; Pandey, Ashutosh N.; Shrivastav, Tulsidas G.; Chaube, Shail K. (2016-03-29). "Impact of stress on oocyte quality and reproductive outcome". Journal of Biomedical Science. 23: 36. doi:10.1186/s12929-016-0253-4. ISSN 1423-0127. PMC 4812655. PMID 27026099.
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