Revisiting ZAR proteins: the understudied regulator of female fertility and beyond

Wu, Yu-Ke; Fan, Heng‐Yu

doi:10.1007/s00018-022-04141-4

Cited by 10 publications

(7 citation statements)

References 64 publications

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“…On the basis of this joint expression matrix, 166 differentially expressed RNA-protein pairs were identified (Figure 4G), and 30 transcript-protein pairs were identified as specific oocyte maturational signatures. Among these pairs, 5 related genes were known biomarkers including CPEB1 36 , GTSF1 37 , GDF9 38 , CELF1 39 , and ZAR1l 40 , while other genes could be considered as potential biomarker candidates.…”

Section: Resultsmentioning

confidence: 99%

Simultaneous transcriptome and proteome profiling in a single mouse oocyte with a deep single-cell multi-omics approach

Jiang

Zhu

Cao

et al. 2022

Preprint

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Nowadays, although single-cell multi-omics technologies are undergoing rapid development, simultaneous transcriptome and proteome analysis of a single-cell individual still faces great challenges. Here, we developed a single-cell simultaneous transcriptome and proteome (scSTAP) analysis platform based on microfluidics, high-throughput sequencing and mass spectrometry technology, to achieve deep and joint quantitative analysis of transcriptome and proteome at the single-cell level for the first time. This platform was applied to analyze single mouse oocytes at different meiotic maturation stages, reaching an average quantification depth of 19948 genes and 2663 protein groups in single mouse oocytes. This reliable quantitative two-omics dataset of single cells provided an important resource for understanding the relationship between the transcriptome and the proteome in cells. Based on the correlation analysis of RNAs and proteins in the same single cell, we demonstrated the expressive heterogeneity of transcriptome and proteome during the cellular biological process. Specially, we analyzed the meiosis regulatory network during oocyte maturation with an unprecedented depth at the single-cell level, and identified 30 transcript-protein pairs as specific oocyte maturational signatures, providing crucial insights into the regulatory features of transcription and translation during oocyte meiotic maturation.

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Section: Resultsmentioning

confidence: 99%

Simultaneous transcriptome and proteome profiling in a single mouse oocyte with a deep single-cell multi-omics approach

Jiang

Zhu

Cao

et al. 2022

Preprint

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“…It has been suggested to promote tumor growth and metastasis in cancer cell lines 38 . ZAR1L (ZAR2) was recognized as a maternal factor with function of maintaining the stability of maternal transcriptome 39 , thereby is important for oogenesis and embryogenesis 40 . Besides, ZAR1L has been suggested potential associated with tumor suppressors, which can repress the transcription of BACA2 to repress breast cancer cells 41 .…”

Section: Discussionmentioning

confidence: 99%

Former smoking associated with epigenetic modifications in human granulosa cells among women undergoing assisted reproduction

Tang,

Gaskins,

Hood

et al. 2024

Sci Rep

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Smoking exposure during adulthood can disrupt oocyte development in women, contributing to infertility and possibly adverse birth outcomes. Some of these effects may be reflected in epigenome profiles in granulosa cells (GCs) in human follicular fluid. We compared the epigenetic modifications throughout the genome in GCs from women who were former (N = 15) versus never smokers (N = 44) undergoing assisted reproductive technologies (ART). This study included 59 women undergoing ART. Smoking history including time since quitting was determined by questionnaire. GCs were collected during oocyte retrieval and DNA methylation (DNAm) levels were profiled using the Infinium MethylationEPIC BeadChip. We performed an epigenome-wide association study with robust linear models, regressing DNAm level at individual loci on smoking status, adjusting for age, ovarian stimulation protocol, and three surrogate variables. We performed differentially methylated regions (DMRs) analysis and over-representation analysis of the identified CpGs and corresponding gene set. 81 CpGs were differentially methylated among former smokers compared to never smokers (FDR < 0.05). We identified 2 significant DMRs (KCNQ1 and RHBDD2). The former smoking-associated genes were enriched in oxytocin signaling, adrenergic signaling in cardiomyocytes, platelet activation, axon guidance, and chemokine signaling pathway. These epigenetic variations have been associated with inflammatory responses, reproductive outcomes, cancer development, neurodevelopmental disorder, and cardiometabolic health. Secondarily, we examined the relationships between time since quitting and DNAm at significant CpGs. We observed three CpGs in negative associations with the length of quitting smoking (p < 0.05), which were cg04254052 (KCNIP1), cg22875371 (OGDHL), and cg27289628 (LOC148145), while one in positive association, which was cg13487862 (PLXNB1). As a pilot study, we demonstrated epigenetic modifications associated with former smoking in GCs. The study is informative to potential biological pathways underlying the documented association between smoking and female infertility and biomarker discovery for smoking-associated reproductive outcomes.

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“…The decreased expression levels of wt1a and wt1b in zebrafish resulted in defects in the development of the kidney and pronephros, as well as embryonic glomerular and tubular cysts [38]. Although those studies have shown that zar1 and wt1 are essential for gonadal differentiation and development, their expressions profiles vary in different species [10,18,25,41,42], and their potential specific functions also need to be further addressed.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, some genes crucial for sex differentiation, including cyp19a1a (cytochrome P450, family 19, subfamily A, polypeptide 1a), foxl2 (forkhead-box protein L2), rspo1 (R-spondin 1), dmrt1 (dsxand mab-3-related transcription factor 1), amh (anti-Mullerian hormone), and sox9 (SRY box 9), usually participate in the process of sex reversal [8]. Recently, other genes like zar1 (zygote arrest-1) and wt1 (Wilms' tumor 1) were also discovered to be closely related to gonadal development [9,10].…”

Section: Introductionmentioning

confidence: 99%

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Characterization of Two Gonadal Genes, zar1 and wt1b, in Hermaphroditic Fish Asian Seabass (Lates calcarifer)

Cui,

Zhu,

Ban

et al. 2024

Animals

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Zygote arrest-1 (Zar1) and Wilms’ tumor 1 (Wt1) play an important role in oogenesis, with the latter also involved in testicular development and gender differentiation. Here, Lczar1 and Lcwt1b were identified in Asian seabass (Lates calcarifer), a hermaphrodite fish, as the valuable model for studying sex differentiation. The cloned cDNA fragments of Lczar1 were 1192 bp, encoding 336 amino acids, and contained a zinc-binding domain, while those of Lcwt1b cDNA were 1521 bp, encoding a peptide of 423 amino acids with a Zn finger domain belonging to Wt1b family. RT-qPCR analysis showed that Lczar1 mRNA was exclusively expressed in the ovary, while Lcwt1b mRNA was majorly expressed in the gonads in a higher amount in the testis than in the ovary. In situ hybridization results showed that Lczar1 mRNA was mainly concentrated in oogonia and oocytes at early stages in the ovary, but were undetectable in the testis. Lcwt1b mRNA was localized not only in gonadal somatic cells (the testis and ovary), but also in female and male germ cells in the early developmental stages, such as those of previtellogenic oocytes, spermatogonia, spermatocytes and spermatids. These results indicated that Lczar1 and Lcwt1b possibly play roles in gonadal development. Therefore, the findings of this study will provide a basis for clarifying the mechanism of Lczar1 and Lcwt1b in regulating germ cell development and the sex reversal of Asian seabass and even other hermaphroditic species.

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Revisiting ZAR proteins: the understudied regulator of female fertility and beyond

Cited by 10 publications

References 64 publications

Simultaneous transcriptome and proteome profiling in a single mouse oocyte with a deep single-cell multi-omics approach

Simultaneous transcriptome and proteome profiling in a single mouse oocyte with a deep single-cell multi-omics approach

Former smoking associated with epigenetic modifications in human granulosa cells among women undergoing assisted reproduction

Characterization of Two Gonadal Genes, zar1 and wt1b, in Hermaphroditic Fish Asian Seabass (Lates calcarifer)

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