ESR2 regulates granulosa cell genes essential for follicle maturation and ovulation. (15th October 2018)

• Record Type: Journal Article
• Authors: Khristi, Vincentaben; Chakravarthi, V. Praveen; Singh, Prabhakar; Ghosh, Subhra; Pramanik, Archit; Ratri, Anamika; Borosha, Shaon; Roby, Katherine F.; Wolfe, Michael W.; Rumi, M.A. Karim
• Is Part Of: Molecular and cellular endocrinology. Volume 474(2018)
• Page Start: 214
• Page End: 226
• Publication Date: 2018-10-15
• Subjects: ESR2 -- Granulosa cells -- Transcriptome analyses -- Follicle maturation -- Ovulation; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2018.03.012
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: Estrogen receptor 2 (ESR2) plays a critical role in folliculogenesis and ovulation. Disruption of ESR2-function in the rats results in female infertility due to failure of ovulation. Ovulation failure occurred in two distinct rat models, a null mutant and a DNA binding domain (DBD) mutant of ESR2, indicating that transcriptional regulation by ESR2 is indispensable for ovulation. To define the regulatory role of ESR2 in preovulatory follicular maturation and ovulation, we investigated ovarian responsiveness to exogenous gonadotropins in prepubertal females. Granulosa cells (GCs) play a vital role in follicle maturation and ovulation, and ESR2-dependent estrogen signaling is predominant in GCs, therefore, we examined the differential expression of gonadotropin-induced genes in GCs. Of 32, 623 genes detected by RNA-sequencing, 1696 were differentially expressed in Esr2 -mutant rats (789 downregulated, and 907 upregulated, absolute fold change 2, FDR p < 0.05). Molecular pathway analyses indicated that these differentially expressed genes are involved in steroidogenesis, follicle maturation, and ovulation. Many of these genes are known regulators of ovarian function and a subset were also disrupted in Esr2 -mutant mice. Interestingly, Kiss1 was identified as one of the differentially expressed genes implicating a potential role within the follicle and its regulation by ESR2. Our findings indicate that ESR2 regulates key genes in GCs that are essential for follicle maturation and ovulation in the rat. Highlights: Estrogen receptor 2 (ESR2) is essential for follicle maturation and ovulation. RNA-seq analyses identified differentially expressed genes in Esr2- mutant granulosa cells. Disruption of ESR2 deregulated key genes involved in follicle maturation, and ovulation. 1696 differentially expressed genes were common in Esr2 null and DBD mutants. Kiss1 was identified as being down regulated in granulosa cells of the Esr2 mutants.