Identification of Biomarkers for Predicting Ovarian Reserve of Primordial Follicle via Transcriptomic Analysis

Abstract

Ovarian reserve (OR) is mainly determined by the number of primordial follicles in the ovary and continuously depleted until ovarian senescence. With the development of assisted reproductive technology such as ovarian tissue cryopreservation and autotransplantation, growing demand has arisen for objective assessment of OR at the histological level. However, no specific biomarkers of OR can be used effectively in clinic nowadays. Herein, bulk RNA-seq datasets of the murine ovary with the biological ovarian age (BOA) dynamic changes and single-cell RNA-seq datasets of follicles at different stages of folliculogenesis were obtained from the GEO database to identify gene signature correlated to the primordial follicle pool. The correlations between gene signature expression and OR were also validated in several comparative OR models. The results showed that genes including Lhx8, Nobox, Sohlh1, Tbpl2, Stk31, and Padi6 were highly correlated to the OR of the primordial follicle pool, suggesting that these genes might be used as biomarkers for predicting OR at the histological level.

PADI6: What we know about the elusive fifth member of the peptidyl arginine deiminase family

“…Recently, single-cell bisulfite and proteomic strategies have been reported and have potential to be highly valuable for the study of early embryonic development in the future [91][92][93][94][95]. The restriction to and abundance of PADI6 in the oocyte and early embryo do hold some clinical advantages; for example, recent studies have highlighted the potential to use PADI6 as a novel marker for oocyte and embryo quality as well as ovarian reserve in women receiving assisted reproductive technologies [96,97].…”

Impacts of vitrification on the transcriptome of human ovarian tissue in patients with gynecological cancer

“…Recently, several studies have used RNA-seq to measure the global transcriptomics of oocytes or follicles (Zhang et al, 2020;Jia et al, 2019;Huang et al, 2018;Wang et al, 2017;Liu et al, 2022). Pereira et al, 2020 reported that vitrification and autotransplantation can affect the transcriptomic expression of mouse ovarian tissue.…”

“…Some genes, such as GDF-9, BMP-4/7/15, KITL, LIF, and FGF-2, are related to primordial follicle growth (Celik et al, 2020). Liu et al (2022) and Sang et al (2021) demonstrated that genes, including Lhx8, Nobox, Sohlh1, Tbpl2, Stk31, and Padi6, might be biomarkers for predicting ovarian reserve. The present study showed that vitrification/warming procedures do not change the aforementioned genes and so these procedures may be a relatively effective method for protecting the ovarian reserve and egg quality.…”

Role of the PADI family in inflammatory autoimmune diseases and cancers: A systematic review

“…In Sertoli cells, the specific expression of PADI2 is involved in testis development by mediating the regulation of target genes by SOX9 regulation ( 12 ). PADI6 is associated with the ovarian reserve (OR) in the primordial follicle pool ( 31 ). During early embryonic development, PADI1 transactivates the early embryonic genome by catalyzing histone tail citrullination.…”

“…PADI4 can induce arteriosclerosis by mediating the formation of NETs or promote tumor growth and metastasis by altering the tumor microenvironment. Furthermore, PADI6 is associated with the ovarian reserve (OR), oocyte maturation and early embryonic development (27)(28)(29)(30)(31)(32).…”