Single-cell RNA sequencing reveals regulation of fetal ovary development in the monkey (Macaca fascicularis)

Abstract

Germ cells are vital for reproduction and heredity. However, the mechanisms underlying female germ cell development in primates, especially in late embryonic stages, remain elusive. Here, we performed single-cell RNA sequencing of 12,471 cells from whole fetal ovaries, and explored the communications between germ cells and niche cells. We depicted the two waves of oogenesis at single-cell resolution and demonstrated that progenitor theca cells exhibit similar characteristics to Leydig cells in fetal monkey ovaries. Notably, we found that ZGLP1 displays differentially expressed patterns between mouse and monkey, which is not overlapped with NANOG in monkey germ cells, suggesting its role in meiosis entry but not in activating oogenic program in primates. Furthermore, the majority of germ cell clusters that sharply express PRDM9 and SPO11 might undergo apoptosis after cyst breakdown, leading to germ cell attrition. Overall, our work provides new insights into the molecular and cellular basis of primate fetal ovary development at single-cell resolution.

Single-Cell Atlas of the Chinese Tongue Sole (Cynoglossus semilaevis) Ovary Reveals Transcriptional Programs of Oogenesis in Fish

“…To better understand the interspecies complexity of germ cell and granulosa cell transcriptomes in fish and mammals, we compared our data with the reported scRNA-seq datasets in macaques ( Zhao et al, 2020a ). To exclude the effects of abiotic factors, the raw data of the macaques and Chinese tongue sole were analysed via the same procedure.…”

“…Macaque UMI matrices were obtained from the NCBI Gene Expression Omnibus (GEO) database (GSE149629). Germ and somatic cells were extracted from the matrix according to the barcode of the cell type reported previously ( Zhao et al, 2020a ).…”

“…In female mammals, follicle cells are anatomically divided into mural granulosa cells and cumulus cells ( Wigglesworth et al, 2015 ). Additionally, some investigators have identified the transcription characteristics of mural granulosa cells and cumulus cells as well as associated signals regulating oogenesis at the single-celllevel ( Fan et al, 2019 ; Zhao et al, 2020a ). The BMP15/GDF9 and NOTCH signaling pathways are thought to be two key pathways that regulate oogenesis ( Eppig et al, 1997 ; Zhang et al, 2011 ).…”

Immune and vascular contributions to organogenesis of the testis and ovary

“…In addition to immunophenotyping, single‐cell RNA sequencing has become a widely used technique to uncover cell identity and heterogeneity and to elucidate dynamic processes during tissue development. Single‐cell RNA sequencing has revealed clear macrophage populations in fetal mouse (E14.5), monkey (E84 and E116), and human (20–26 weeks) ovaries [60–62]. CD14+ primitive monocytes and activated MHCII+ monocyte‐derived cells were present in human fetal ovaries at 24 weeks of gestation [63], supporting reports of ovarian macrophages in the fetal ovary.…”

Exposures during the prepuberty period and future offspring’s health: evidence from human cohort studies†

“…After sex determination, female PGCs arrive at the developing ovaries and proliferate with an incomplete cytoplasmic mitosis to form oogonia cysts and subsequently initiate meiosis to become meiocytes [63]. The developmental trajectories of embryonic female germ cells are described both in humans and mice [57,58,64,65]. The mitosis to meiosis transition is accompanied by drastic changes in transcriptomes and represents a crucial event during early female germ cell development.…”