Oocyte development, meiosis and aneuploidy

Abstract

Meiosis is one of the defining events in gametogenesis. Male and female germ cells both undergo one round of meiotic cell division during their development in order to reduce the ploidy of the gametes, and thereby maintain the ploidy of the species after fertilisation. However, there are some aspects of meiosis in the female germline, such as the prolonged arrest in dictyate, that appear to predispose oocytes to missegregate their chromosomes and transmit aneuploidies to the next generation. These maternally-derived aneuploidies are particularly problematic in humans where they are major contributors to miscarriage, age-related infertility, and the high incidence of Down's syndrome in human conceptions. This review will discuss how events that occur in foetal oocyte development and during the oocytes’ prolonged dictyate arrest can influence meiotic chromosome segregation and the incidence of aneuploidy in adult oocytes.

Physiological Aspects of Female Fertility: Role of the Environment, Modern Lifestyle, and Genetics

“…As described previously as the woman's age increases, the chiasmata more proximal to the telomere become more susceptible to missegregation as there is believed to be less cohesion between the sister chromatids, due to an age-related loss in cohesin and shugoshin cohesions proteins, as they are produced in fetal life and deteriorate with time and exposure to reactive oxygen species (ROS) (136,208). Another reported peculiarity of the human oocyte is the slow meiotic spindle formation compared with the mouse, and consequent predisposition to spindle instability and anaphase lag whereby due to slow segregation of the chromosomes an aneuploid chromosomal constitution may arise upon cytokinesis (154).…”

“…The centrosome, responsible for the subsequent spindle and microtubule development within the embryo, is derived from the sperm, hence men with significant impairment in spermatogenesis, and oligospermia, may be responsible for higher rates of aneuploidy (the gain or loss of whole chromosomes) within the subsequent embryo (209,339). However, the most common cause of embryo aneuploidy is related to female age as the oocyte has been in a stage of arrested meiotic development in prophase since early fetal life, hence as a woman ages and is exposed to reactive oxygen species within the environment, there is a progressive loss of cohesion molecules that hold sister chromatids together, the incidence of aneuploidy increases exponentially (114), particularly the chiasmata proximal to the telomere (208). This is exacerbated by deterioration in cytoplasmic mitochondria and mRNA stores (369).…”

Sirt2‐BubR1 acetylation pathway mediates the effects of advanced maternal age on oocyte quality

“…The majority of aneuploid embryos are nonviable and spontaneously aborted. The frequency of meiotic defects and aneuploidy in oocytes is strongly associated with maternal age and increases exponentially in the decade preceding the menopause (MacLennan, Crichton, Playfoot, & Adams, 2015; Nagaoka, Hassold, & Hunt, 2012). …”

SMC5/6 is required for the formation of segregation-competent bivalent chromosomes during meiosis I in mouse oocytes

“…As women age, their oocytes become more susceptible to chromosome missegregation, which can lead to infertility and developmental abnormalities (Hassold and Hunt, 2001). Therefore, it is important to determine the molecular pathways that are prone to error in oocytes, especially the proteins required for monitoring and facilitating chromosome segregation (MacLennan et al, 2015).…”