{"id":1785,"date":"2023-07-20T15:56:40","date_gmt":"2023-07-20T15:56:40","guid":{"rendered":"https:\/\/blog.antoniolamarca.it\/?p=1785"},"modified":"2024-03-11T08:37:17","modified_gmt":"2024-03-11T08:37:17","slug":"sperm-quality-decreases-with-lethality-2-2","status":"publish","type":"post","link":"https:\/\/blog.antoniolamarca.it\/en\/sperm-quality-decreases-with-lethality-2-2\/","title":{"rendered":"WHY DOES OOCYTE QUALITY DECLINE WITH AGE?"},"content":{"rendered":"Reading Time: <\/span> 4<\/span> minutes<\/span><\/span>

Unlike men who possess a renewable population of germ cells, women begin life with a finite number of oocytes. The oocytes in the primordial follicle pool (ovarian reserve) decrease in number during a woman's lifetime. Gametogenesis begins during foetal development and, by the fifth month of embryonic development, the number of germ cells, called oocytes, reaches a peak number of about 6-7 million. After reaching this peak, they undergo major atresia leading to a reduction in the follicular pool; the surviving oogonia enter the prophase of the first meiotic division and transform into primary oocytes, surrounded by flat epithelial cells and thus form the primordial follicle pool. The primary oocytes remain stationary in prophase in the diplotene stage and do not complete their first meiotic division until puberty is reached. At birth there are approximately between one million and 700,000 follicles, but the process of atresia continues into extrauterine life and, by puberty, approximately 400,000 primordial follicles remain. During the female reproductive life span, under the influence of intra- and extra-ovarian factors, follicles cyclically resume their meiotic growth phases. This rate of primordial follicle recruitment increases with age and is reciprocally related to ovarian reserve. A woman's biological fertility capacity declines with age, similar to other species: it peaks around the age of 20, then declines sharply from the age of 35 and ends with menopause at the average age of 51. Changes in the ovarian follicle pool and the decrease in ovarian reserve are the main causes of the decline in female reproductive capacity.<\/span><\/p>\n

Ovarian ageing has been the subject of scientific investigation for decades. It is scientifically well known that advancing maternal age correlates with a rapid decline in the production of oocytes in terms of quantity and quality, i.e. oocytes competent for fertilisation and subsequent embryonic development, leading to a downward slope of the fertility curve. Ovarian ageing is likely to depend on multiple intra-ovarian and extra-ovarian factors. With advancing maternal age, chromosome segregation errors during meiotic divisions are increasingly common and lead to the production of oocytes with an incorrect number of chromosomes, a condition known as aneuploidy. When an aneuploid oocyte is fertilised by a spermatozoon, it gives rise to an aneuploid embryo which, except in rare situations, will result in a miscarriage. To remedy this, it is essential that sister chromatids remain together until a precise moment in cell division called anaphase. Cohesins are multi-protein complexes that mediate cohesion between sister chromatid arms, and with increasing female age, chromosome cohesion in oocytes naturally deteriorates. The decrease in cohesion leads to a higher frequency of chromosome mis-segregation, premature chromatid separation and subsequent aneuploidy. Several mechanisms have been proposed to explain the higher incidence of oocyte aneuploidy in women over 35, such as recombination failure, cohesion deterioration, meiotic spindle assembly checkpoint dysregulation, telomere shortening, abnormalities in post-translational modification of histones or mitochondrial dysfunction. At least 10% of pregnancies are trisomic or monosomic and usually due to oocyte aneuploidy, whereas mis-segregation in male germ cells is rarer and occurs in about 2% of cases. As organisms age, the cellular mechanisms that repair DNA damage become less effective. The reduced effectiveness of DNA repair mechanisms leads to DNA damage, impaired repair and accumulation of mutations. In oocytes, this may lead to poor quality, apoptosis and, ultimately, infertility and miscarriage. Recently, importance has also been given to the extrafollicular ovarian environment, as it seems to have a direct or indirect impact on the developing gamete; this environment undergoes age-dependent changes such as increased fibrosis of the ovarian stroma, caused by an accumulation of extracellular matrix (ECM) in which there is increased collagen synthesis and reduced deposition of hyaluronic acid. Starting at puberty, the cyclic remodelling of the ovarian extracellular matrix due to follicle maturation and atresia leads to a gradual increase in immune cell populations, mainly macrophages. In parallel with age-associated fibrosis, stromal cells change in number and function and increase the expression of genes involved in the recruitment of immune cells and inflammatory factors.\u00a0 <\/span>Ageing is also\u00a0 <\/span>characterised by a state of chronic low-grade inflammation, stiffness and oxidative damage. With regard to oxidative damage, cells are normally able to eliminate ROS (reactive oxygen species), which, when produced in excess, cause oxidative stress and damage to mitochondrial and nuclear DNA up to apoptosis. ROS are among the most important physiological inducers of cellular damage associated with ageing. It has been shown that oxidative damage caused by ROS can impact reproductive potential by decreasing the quality of ovarian follicles and oocytes, and that antioxidants can prevent oxidative damage and delay oocyte ageing. ROS can be lethal for cells, but they are still part of the normal ovarian ageing process, which involves a decreased capacity to eliminate them.\u00a0<\/span><\/p>\n

Ultimately, there are multiple mechanisms that contribute to the decline in oocyte quality that is observed with ageing. These changes not only affect the quality of embryo development before and after implantation, but also subsequent extra-uterine life. The extent of this multifactorial impact on oocyte quality and ovarian ageing is under ongoing study and encourages the search for reliable predictors of oocyte quality and possible protective factors that could delay these natural processes.<\/p>\n

REFERENCES<\/strong><\/p>\n

Ali Reza Eftekhari Moghadam,\u00a0<\/span>Mahin Taheri Moghadam,<\/span>Masoud Hemadi,and\u00a0<\/span>Ghasem Saki, Oocyte quality and aging. <\/span>JBRA Assist Reprod.\u00a02022 Jan-Mar; 26(1): 105-122<\/span><\/p>\n

Myy Mikwar\u00a0<\/sup><\/span>, Amanda J MacFarlane\u00a0<\/sup><\/span>, Francesco Marchetti\u00a0. <\/sup><\/span>Mechanisms of oocyte aneuploidy associated with advanced maternal age. utat Res Rev Mutat Res. 2020 Jul-Sep;785:108320<\/p>\n

Selena U Park\u00a0<\/sup><\/span>Leann Walsh\u00a0<\/sup><\/span>Karen M Berkowitz. Mechanisms of ovarian aging. Eproduction. 2021 Jul 14;162(2):R19-R33.\u00a0 <\/span>doi: 10.1530\/REP-21-0022<\/p>\n

Antonella Camaioni, Maria Assunta Ucci, Luisa Campagnolo, Massimo De Felici, Francesca Gioia Klinger ; Italian Society of Embryology, Reproduction and Research (SIERR). The process of ovarian aging: it is not just about oocytes and granulosa cells. Assist Reprod Genet. 2022 Apr;39(4):783-792.\u00a0 <\/span>doi: 10.1007\/s10815-022-02478-0<\/p>\n

Jan Tesarik, Maribel Gal\u00e1n-L\u00e1zaro, Raquel Mendoza-Tesarik. Ovarian Aging: Molecular Mechanisms and Medical Management. t J Mol Sci. 2021 Jan 29;22(3):1371.<\/p>","protected":false},"excerpt":{"rendered":"

Reading Time: <\/span> 4<\/span> minutes<\/span><\/span> Unlike men who possess a renewable population of germ cells, women begin life with a finite number of oocytes. The oocytes included in the primordial follicle pool (ovarian reserve) decrease in number during a woman's lifetime. Gametogenesis begins during foetal development and, by the fifth month ...<\/p>","protected":false},"author":1,"featured_media":1789,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"single-classic-ns.php","format":"standard","meta":{"om_disable_all_campaigns":false,"footnotes":""},"categories":[5,2],"tags":[],"class_list":["post-1785","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-featured","category-press"],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/blog.antoniolamarca.it\/en\/wp-json\/wp\/v2\/posts\/1785","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/blog.antoniolamarca.it\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blog.antoniolamarca.it\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blog.antoniolamarca.it\/en\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/blog.antoniolamarca.it\/en\/wp-json\/wp\/v2\/comments?post=1785"}],"version-history":[{"count":2,"href":"https:\/\/blog.antoniolamarca.it\/en\/wp-json\/wp\/v2\/posts\/1785\/revisions"}],"predecessor-version":[{"id":1787,"href":"https:\/\/blog.antoniolamarca.it\/en\/wp-json\/wp\/v2\/posts\/1785\/revisions\/1787"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/blog.antoniolamarca.it\/en\/wp-json\/wp\/v2\/media\/1789"}],"wp:attachment":[{"href":"https:\/\/blog.antoniolamarca.it\/en\/wp-json\/wp\/v2\/media?parent=1785"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blog.antoniolamarca.it\/en\/wp-json\/wp\/v2\/categories?post=1785"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blog.antoniolamarca.it\/en\/wp-json\/wp\/v2\/tags?post=1785"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}