| First Author | Lee EB | Year | 2024 |
| Journal | Int J Mol Sci | Volume | 25 |
| Issue | 6 | PubMed ID | 38542176 |
| Mgi Jnum | J:348989 | Mgi Id | MGI:7617579 |
| Doi | 10.3390/ijms25063202 | Citation | Lee EB, et al. (2024) Loss of ERbeta Disrupts Gene Regulation in Primordial and Primary Follicles. Int J Mol Sci 25(6) |
| abstractText | Loss of ERbeta increases primordial follicle growth activation (PFGA), leading to premature ovarian follicle reserve depletion. We determined the expression and gene regulatory functions of ERbeta in dormant primordial follicles (PdFs) and activated primary follicles (PrFs) using mouse models. PdFs and PrFs were isolated from 3-week-old Erbeta knockout (Erbeta(null)) mouse ovaries, and their transcriptomes were compared with those of control Erbeta(fl/fl) mice. We observed a significant (>/=2-fold change; FDR p-value </= 0.05) deregulation of approximately 5% of genes (866 out of 16,940 genes, TPM >/= 5) in Erbeta(null) PdFs; ~60% (521 out of 866) of the differentially expressed genes (DEGs) were upregulated, and 40% were downregulated, indicating that ERbeta has both transcriptional enhancing as well as repressing roles in dormant PdFs. Such deregulation of genes may make the Erbeta(null) PdFs more susceptible to increased PFGA. When the PdFs undergo PFGA and form PrFs, many new genes are activated. During PFGA of Erbeta(fl/fl) follicles, we detected a differential expression of ~24% genes (4909 out of 20,743; >/=2-fold change; FDR p-value </= 0.05; TPM >/= 5); 56% upregulated and 44% downregulated, indicating the gene enhancing and repressing roles of Erbeta-activated PrFs. In contrast, we detected a differential expression of only 824 genes in Erbeta(null) follicles during PFGA (>/=2-fold change; FDR p-value </= 0.05; TPM >/= 5). Moreover, most (~93%; 770 out of 824) of these DEGs in activated Erbeta(null) PrFs were downregulated. Such deregulation of genes in Erbeta(null) activated follicles may impair their inhibitory role on PFGA. Notably, in both Erbeta(null) PdFs and PrFs, we detected a significant number of epigenetic regulators and transcription factors to be differentially expressed, which suggests that lack of ERbeta either directly or indirectly deregulates the gene expression in PdFs and PrFs, leading to increased PFGA. |
