Transcriptional progression during meiotic prophase I reveals sex-specific features and X chromosome dynamics in human fetal female germline

Abstract

During gametogenesis in mammals, meiosis ensures the production of haploid gametes. The timing and length of meiosis to produce female and male gametes differ considerably. In contrast to males, meiotic prophase I in females initiates during development. Hence, the knowledge regarding progression through meiotic prophase I is mainly focused on human male spermatogenesis and female oocyte maturation during adulthood. Therefore, it remains unclear how the different stages of meiotic prophase I between human oogenesis and spermatogenesis compare. Analysis of single-cell transcriptomics data from human fetal germ cells (FGC) allowed us to identify the molecular signatures of female meiotic prophase I stages leptotene, zygotene, pachytene and diplotene. We have compared those between male and female germ cells in similar stages of meiotic prophase I and revealed conserved and specific features between sexes. We identified not only key players involved in the process of meiosis, but also highlighted the molecular components that could be responsible for changes in cellular morphology that occur during this developmental period, when the female FGC acquire their typical (sex-specific) oocyte shape as well as sex-differences in the regulation of DNA methylation. Analysis of X-linked expression between sexes during meiotic prophase I suggested a transient X-linked enrichment during female pachytene, that contrasts with the meiotic sex chromosome inactivation in males. Our study of the events that take place during meiotic prophase I provide a better understanding not only of female meiosis during development, but also highlights biomarkers that can be used to study infertility and offers insights in germline sex dimorphism in humans.

Characterization of the human fetal rete region by single cell transcriptional analysis of gonads and mesonephros/epididymis

“…In mice, single cell transcriptomics has been applied to investigate the developmental stages and cellular trajectories during male gametogenesis (Chen et al, 2018), but the molecular identity of the rete testis was not explored. Similarly, single cell transcriptomics in humans has been used to study testis development and gametogenesis during fetal and adult life (Fan et al, 2021, Guo et al, 2018, Guo et al, 2021, Li et al, 2017, Shami et al, 2020, Sohni et al, 2019, Wang et al, 2018). However, the molecular signatures of the rete testis have not been inferred and differences with the mesonephros remain to be determined.…”

Application of single-cell RNA sequencing on human testicular samples: a comprehensive review

“…Besides, it's well known that ovary is the female counterpart of the testis, thus scientists tried to compare gonads of two genders. The conservatism of germ cells for both genders was observed during meiotic prophase I, such as the high expression of the same marker genes at each stage of primary SPC/oocytes ( TEX19 in leptotene; SPO11 in zygotene; BRDT in pachytene and H1FOO in diplotene) 172 . Wang et al even identified shared subtypes of germ cells (SPARC + fetal germ cells) in prenatal testes and ovaries 82 .…”

“…Wang et al even identified shared subtypes of germ cells (SPARC + fetal germ cells) in prenatal testes and ovaries 82 . But huge heterogeneity of germ cells was also reported in the expression of X-linked genes, including the high expression of SMS in diplotene oocytes but not SPC and the lack of XIST in adult testes 73 , 172 . Both homogeneity and diversity between genders were also reported in somatic cells during scRNA-seq analyses.…”

Dynamic Responses of Chromosome-Binding Protein Complexes to Meiotic Prophase I of Mouse Spermatocyte

“…In the category of the preinitiation complex (PIC) of transcription, six complexes were detected, and the complex abundance was basically presented in two phase-dependent modes, upregulated in L and Z or P and D. Although the phase-dependent transcription changes in MPI have been studied, the relevant transcription complexes at each phase of MPI have not yet been reported. This study monitored the complex abundance responses to the MPI process for the first time.…”