Regulation of Meiotic Prophase One in Mammalian Oocytes

Abstract

In female mammals, meiotic prophase one begins during fetal development. Oocytes transition through the prophase one substages consisting of leptotene, zygotene, and pachytene, and are finally arrested at the diplotene substage, for months in mice and years in humans. After puberty, luteinizing hormone induces ovulation and meiotic resumption in a cohort of oocytes, driving the progression from meiotic prophase one to metaphase two. If fertilization occurs, the oocyte completes meiosis two followed by fusion with the sperm nucleus and preparation for zygotic divisions; otherwise, it is passed into the uterus and degenerates. Specifically in the mouse, oocytes enter meiosis at 13.5 days post coitum. As meiotic prophase one proceeds, chromosomes find their homologous partner, synapse, exchange genetic material between homologs and then begin to separate, remaining connected at recombination sites. At postnatal day 5, most of the oocytes have reached the late diplotene (or dictyate) substage of prophase one where they remain arrested until ovulation. This review focuses on events and mechanisms controlling the progression through meiotic prophase one, which include recombination, synapsis and control by signaling pathways. These events are prerequisites for proper chromosome segregation in meiotic divisions; and if they go awry, chromosomes mis-segregate resulting in aneuploidy. Therefore, elucidating the mechanisms regulating meiotic progression is important to provide a foundation for developing improved treatments of female infertility.

SPIDR is required for homologous recombination during mammalian meiosis

“…To determine whether the loss of follicles within three months in Spidr −/− female mice was caused by the defective meiosis progression, ovaries dissected from E13.5 (embryonic day 13.5), E15.5 (embryonic day 15.5) and PD1 (postnatal day 1) mice were immunostained with mouse vasa homolog (MVH) antibody in which MVH marks for primordial germ cells ( 45 ). Quantification of relative numbers of oocytes showed that there were comparable numbers of oocytes in WT and Spidr −/− ovaries at E13.5 when meiosis is initiated (Figure 5A – C ) and at E15.5 when the oocytes are just entering the pachytene stage (Figure 5D – F ) ( 46 ). However, there was only 8.2% oocytes in Spidr −/− ovaries compared to WT ovaries at PD1 (Figure 5G – I ).…”

Robust and Efficient Active Genetics Gene Conversion in the Rat and Mouse

“…These findings underline the value of having more than one gRNA site near the target gene conversion location(s). Given the complexity of the gene conversion pathways (Kockler et al, 2021), meiosis (Zickler and Kleckner, 2015; Bolcun-Filas and Handel, 2018), and gamete development (Ernest et al, 2019; Wang and Pepling; 2021; Zamboni et al, 1972), processes involving thousands of proteins and hundreds of steps, the strength of these correlations is remarkable. They reinforce the conclusion that timing and levels of Cas9 activity in the developing gamete are critical. The correlation between Cas9 level and AG efficiency in the mouse is not strong as in the rat, we believe that this low correlation is driven by the low levels of mouse AG efficiency seen, in the 0-3% range.…”

Epigenetic aging of mammalian gametes

“…The epigenome becomes much more stable once the oocyte has reached the cell cycle arrest stage (dictyate stage) during embryonic development (Fan et al, 2021; He et al, 2021; Hu et al, 2022; Spradling et al, 2022). Oocytes are arrested then before the initiation of MI and await signals that will initiate ovulation (Wang & Pepling, 2021). Just before birth, a selection‐based event termed Fetal Oocyte Attrition reduces mouse and human oocytes numbers by ~75% (Rodrigues et al, 2009).…”