Meiotic onset is reliant on spatial distribution but independent of germ cell number in the mouse ovary

Abstract

Mouse ovarian germ cells enter meiosis in a wave that propagates from anterior to posterior, but little is known about contribution of germ cells to initiation or propagation of meiosis. In a Ror2 mutant with diminished germ cell number and migration, we find that overall timing of meiotic initiation is delayed at the population level. We use chemotherapeutic depletion to exclude a profoundly reduced number of germ cells as a cause for meiotic delay. We rule out sex reversal or failure to specify somatic support cells as contributors to the meiotic phenotype. Instead, we find that anomalies in the distribution of germ cells as well as gonad shape in mutants contribute to aberrant initiation of meiosis. Our analysis supports a model of meiotic initiation via diffusible signal(s), excludes a role for germ cells in commencing the meiotic wave and furnishes the first phenotypic demonstration of the wave of meiotic entry. Finally, our studies underscore the importance of considering germ cell migration defects while studying meiosis to discern secondary effects resulting from positioning versus primary meiotic entry phenotypes.

Two distinct pathways of pregranulosa cell differentiation support follicle formation in the mouse ovary

“…Most germ cells (83.0%) at E12.5 were classified as premeiotic. E14.5 germ cells were heterogeneous in stage (preleptotene, 16.1%; leptotene, 57.5%; and zygotene, 22.4%), reflecting differences in the time when PGC cells arrive at the gonad, as well as the anterior-posterior gradient of differentiation (37,68). Most E16.5 cells were in pachytene (45) and had transitioned to diplotene by E18.5 (69).…”

The antiandrogenic vinclozolin induces differentiation delay of germ cells and changes in energy metabolism in 3D cultures of fetal ovaries

“…Later, around 13.5 dpc, oogonia cells initiate meiosis and progress through meiotic prophase I up to dictyotene, remaining in that stage until meiotic resumption (after birth about 20 dpc). Meiotic prophase I is not fully synchronized, and during the first days of meiotic initiation, it is possible to observe mitotically active oogonia and oocytes having already entered meiotic prophase I during the first days of meiotic initiation 6 . The transition from cysts to individual follicles is initiated from 17.5 dpc, along with the beginning of follicular atresia, when only the surviving oocytes, as in other mammals, are surrounded by pre-granulosa cells 7 – 9 .…”

Escort-like somatic cells mediate early mouse fetal ovarian development but surface-derived Lgr5+ cells support primordial follicles

“…By generating single cell transcriptomes from more than 24,000 cells isolated from E12.5 to P5 mouse ovaries, we gained significant new insight into the cellular and genetic foundations of oogenesis. At any given age, ovarian germ cells vary by more than 24 hours in developmental stage, due to PGC asynchrony and meiotic initiation in an anterior to posterior wave during this period (Arora et al, 2016;Bullejos and Koopman, 2004;Menke et al, 2003). However, by reconstructing developmental trajectories based on gene expression we showed that data from germ cells aligned on a single pseudotimeline of cellular and meiotic development ( Figure 1D).…”