Ovum quality

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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]

Contents

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]

Related Research Articles

<span class="mw-page-title-main">Meiosis</span> Cell division producing haploid gametes

Meiosis is a special type of cell division of germ cells and apicomplexans in sexually-reproducing organisms that produces the gametes, such as sperm or egg cells. It involves two rounds of division that ultimately result in four cells with only one copy of each chromosome (haploid). Additionally, prior to the division, genetic material from the paternal and maternal copies of each chromosome is crossed over, creating new combinations of code on each chromosome. Later on, during fertilisation, the haploid cells produced by meiosis from a male and a female will fuse to create a cell with two copies of each chromosome again, the zygote.

<span class="mw-page-title-main">Ovary</span> Female reproductive organ that produces egg cells

The ovary is an organ in the female reproductive system that produces an ovum. When released, this travels down the fallopian tube into the uterus. There is an ovary found on the left and the right side of the body. The ovaries also secrete hormones that play a role in the menstrual cycle and fertility. The ovary progresses through many stages beginning in the prenatal period through menopause. It is also an endocrine gland because of the various hormones that it secretes.

<span class="mw-page-title-main">Germ cell</span> Gamete-producing cell

A germ cell is any cell that gives rise to the gametes of an organism that reproduces sexually. In many animals, the germ cells originate in the primitive streak and migrate via the gut of an embryo to the developing gonads. There, they undergo meiosis, followed by cellular differentiation into mature gametes, either eggs or sperm. Unlike animals, plants do not have germ cells designated in early development. Instead, germ cells can arise from somatic cells in the adult, such as the floral meristem of flowering plants.

<span class="mw-page-title-main">Nondisjunction</span> Failure to separate properly during cell division

Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate properly during cell division (mitosis/meiosis). There are three forms of nondisjunction: failure of a pair of homologous chromosomes to separate in meiosis I, failure of sister chromatids to separate during meiosis II, and failure of sister chromatids to separate during mitosis. Nondisjunction results in daughter cells with abnormal chromosome numbers (aneuploidy).

An oocyte, oöcyte, or ovocyte is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in a female fetus in the ovary during female gametogenesis. The female germ cells produce a primordial germ cell (PGC), which then undergoes mitosis, forming oogonia. During oogenesis, the oogonia become primary oocytes. An oocyte is a form of genetic material that can be collected for cryoconservation.

<span class="mw-page-title-main">Oogenesis</span> Egg cell production process

Oogenesis, ovogenesis, or oögenesis is the differentiation of the ovum into a cell competent to further develop when fertilized. It is developed from the primary oocyte by maturation. Oogenesis is initiated in the embryonic stage.

<span class="mw-page-title-main">Human reproductive system</span> Organs involved in reproduction

The human reproductive system includes the male reproductive system which functions to produce and deposit sperm; and the female reproductive system which functions to produce egg cells, and to protect and nourish the fetus until birth. Humans have a high level of sexual differentiation. In addition to differences in nearly every reproductive organ, there are numerous differences in typical secondary sex characteristics.

<span class="mw-page-title-main">Folliculogenesis</span> Process of maturation of primordial follicles

In biology, folliculogenesis is the maturation of the ovarian follicle, a densely packed shell of somatic cells that contains an immature oocyte. Folliculogenesis describes the progression of a number of small primordial follicles into large preovulatory follicles that occurs in part during the menstrual cycle.

<span class="mw-page-title-main">Human fertilization</span> Union of a human egg and sperm

Human fertilization is the union of a human egg and sperm, occurring primarily in the ampulla of the fallopian tube. The result of this union leads to the production of a fertilized egg called a zygote, initiating embryonic development. Scientists discovered the dynamics of human fertilization in the 19th century.

<span class="mw-page-title-main">Polar body</span> Byproduct of oogenesis

A polar body is a small haploid cell that is formed at the same time as an egg cell during oogenesis, but generally does not have the ability to be fertilized. It is named from its polar position in the egg.

<span class="mw-page-title-main">Sister chromatids</span> Two identical copies of a chromosome joined at the centromere

A sister chromatid refers to the identical copies (chromatids) formed by the DNA replication of a chromosome, with both copies joined together by a common centromere. In other words, a sister chromatid may also be said to be 'one-half' of the duplicated chromosome. A pair of sister chromatids is called a dyad. A full set of sister chromatids is created during the synthesis (S) phase of interphase, when all the chromosomes in a cell are replicated. The two sister chromatids are separated from each other into two different cells during mitosis or during the second division of meiosis.

An immature ovum is a cell that goes through the process of oogenesis to become an ovum. It can be an oogonium, an oocyte, or an ootid. An oocyte, in turn, can be either primary or secondary, depending on how far it has come in its process of meiosis.

Chromosome segregation is the process in eukaryotes by which two sister chromatids formed as a consequence of DNA replication, or paired homologous chromosomes, separate from each other and migrate to opposite poles of the nucleus. This segregation process occurs during both mitosis and meiosis. Chromosome segregation also occurs in prokaryotes. However, in contrast to eukaryotic chromosome segregation, replication and segregation are not temporally separated. Instead segregation occurs progressively following replication.

<span class="mw-page-title-main">Homology directed repair</span>

Homology-directed repair (HDR) is a mechanism in cells to repair double-strand DNA lesions. The most common form of HDR is homologous recombination. The HDR mechanism can only be used by the cell when there is a homologous piece of DNA present in the nucleus, mostly in G2 and S phase of the cell cycle. Other examples of homology-directed repair include single-strand annealing and breakage-induced replication. When the homologous DNA is absent, another process called non-homologous end joining (NHEJ) takes place instead.

The origin and function of meiosis are currently not well understood scientifically, and would provide fundamental insight into the evolution of sexual reproduction in eukaryotes. There is no current consensus among biologists on the questions of how sex in eukaryotes arose in evolution, what basic function sexual reproduction serves, and why it is maintained, given the basic two-fold cost of sex. It is clear that it evolved over 1.2 billion years ago, and that almost all species which are descendants of the original sexually reproducing species are still sexual reproducers, including plants, fungi, and animals.

Oocyteactivation is a series of processes that occur in the oocyte during fertilization.

<span class="mw-page-title-main">STAG3 (gene)</span> Protein-coding gene in the species Homo sapiens

Stromal antigen 3 is a protein that in humans is encoded by the STAG3 gene. STAG3 protein is a component of a cohesin complex that regulates the separation of sister chromatids specifically during meiosis. STAG3 appears to be paramount in sister-chromatid cohesion throughout the meiotic process in human oocytes and spermatocytes.

Obesity is defined as an abnormal accumulation of body fat, usually 20% or more over an individual's ideal body weight. This is often described as a body mass index (BMI) over 30. However, BMI does not account for whether the excess weight is fat or muscle, and is not a measure of body composition. For most people, however, BMI is an indication used worldwide to estimate nutritional status. Obesity is usually the result of consuming more calories than the body needs and not expending that energy by doing exercise. There are genetic causes and hormonal disorders that cause people to gain significant amounts of weight but this is rare. People in the obese category are much more likely to suffer from fertility problems than people of normal healthy weight.

Achiasmate Meiosis refers to meiosis without chiasmata, which are structures that are necessary for recombination to occur and that usually aid in the segregation of non-sister homologs. The pachytene stage of prophase I typically results in the formation of chiasmata between homologous non-sister chromatids in the tetrad chromosomes that form. The formation of a chiasma is also referred to as crossing over. When two homologous chromatids cross over, they form a chiasma at the point of their intersection. However, it has been found that there are cases where one or more pairs of homologous chromosomes do not form chiasmata during pachynema. Without a chiasma, no recombination between homologs can occur.

Oocytes are immature egg cells that develop to maturity within a follicle in the ovary. Oocyte abnormalities can occur due to several factors, including premature ovarian insufficiency (POI), other maturation abnormalities, maternal ageing, and mitochondrial abnormalities.

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. S2CID   10691804.
  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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
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