Current understanding of meiosis initiation and regulation is primarily derived from studies in mice, and it is generally accepted that the onset of meiosis depends on exposure to retinoic acid. In fetal ovaries, the first signs of meiosis initiation are apparent between embryonic day 12.5 and 13.5 in mice ( Adams & McLaren 2002) and from gestational week 12 in humans ( Gondos et al.

Although meiosis is comprised of two rounds of cell division, only prophase of meiosis I occurs during fetal oogenesis, with arrest occurring before completion of the first division. The initiation of meiosis is one of the defining features of germ cell differentiation and occurs in fetal life in female mammals. These follicles are produced from primordial germ cells which transition to oocytes as they undergo loss of pluripotency, proliferate with incomplete cytokinesis forming germ cell nests, and enter into meiosis. These data therefore indicate that retinoic acid is not necessary for meiotic progression but may have a role in the regulation of its progression and germ cell survival at that time and provide evidence for a link between meiotic arrest and follicle growth initiation.ДЇemale reproductive senescence results from the depletion of a finite ovarian follicle pool that is assembled during fetal life. Furthermore, ovaries treated with WIN 18,446 at e13.5 but not at P0 had a higher proportion of growing follicles compared to vehicle controls, thus showing evidence of increased follicle activation. WIN 18,446 significantly accelerated the progression of prophase I this was seen as early as 48 h post treatment using meiotic chromosome spreads and was still evident after 12 days of culture using Tra98/Msy2 immunostaining. Higher doses resulted in germ cell loss, rescued with the addition of retinoic acid. Doses as low as 0.01 ВµM reduced transcript levels of the retinoic acid response genes Stra8 and RarОІ without affecting germ cell number. e13.5 mouse fetal ovaries were cultured in vitro and treated with WIN 18,446 for the first 3 days of a total of up to 12 days. WIN 18,446 inhibits the conversion of retinol to retinoic acid, and therefore it was used to explore the impact of reduced retinoic acid synthesis on meiotic progression and thus germ cell development and subsequent primordial follicle formation. Initiation of meiosis is one of the defining features of germ cell differentiation and is well established to commence in response to retinoic acid. Furthermore, chromatids from a maternal chromosome are said to be non-sister chromatids to the homologous paternal chromosome.In female mammals, reproductive potential is determined during fetal life by the formation of a non-renewable pool of primordial follicles. In other words, unreplicated and replicated chromosomes are considered single chromosomes, even though replicated chromosomes have two copies of DNA strands attached.

Each pair of connected sister chromatids are called chromosomes: one maternal chromosome (with two sister chromatids) and one paternal chromosome (also with two sister chromatids). Each homologous pair of chromosomes has two pairs of sister chromatids. The replicated strands are called sister chromatids, which are identical copies of each other connected at the centromere. During the S phase, the unreplicated chromosomes replicate. These are known as unreplicated chromosomes.

Prior to the S phase, each homologous pair of chromosomes (one paternal and one maternal chromosome of the same type) are unreplicated. It is important to be able to understand chromosomal terminology to fully understand meiosis. During interphase before meiosis begins, chromosomes duplicate and produce sister chromatids of each chromosome.

Prophase one