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Transcriptome datasets of ESR2-regulated genes in rat granulosa cells during gonadotropin-induced follicle maturation.

ABSTRACT: Disruption of estrogen receptor beta (ESR2) dysregulates granulosa cell genes essential for follicle maturation and ovulation. The datasets presented in this article depict gonadotropin-induced genes, which are differentially expressed in Esr2-null rat granulosa cells. Synchronized follicle development was initiated in four-week-old wildtype and Esr2-null female rats by administration of PMSG. Forty-eight hours after PMSG injection, further maturation of ovarian follicles was induced by hCG treatment. Granulosa cells were collected from the ovaries before gonadotropin administration, 48?h after PMSG treatment, and 4?h after hCG injection to the PMSG-treated rats. Total RNA was purified from granulosa cells and whole transcriptome was assessed by RNA-sequencing on an Illumina HiSeq X platform. RNA-seq data of wildtype and Esr2-null granulosa cells were analyzed and differentially expressed genes were identified by CLC Genomics Workbench. Gonadotropin-induced genes were identified by comparing the transcriptome data of PMSG- or hCG-induced wildtype granulosa cells with those without gonadotropin treatment. Furthermore, differentially expressed genes in Esr2-null granulosa cells were determined by comparing the transcriptome data with that of wildtype granulosa cells. These datasets can be used to recognize the gonadotropin-induced genes in granulosa cells that are Esr2-regulated and important for ovarian follicle maturation.

SUBMITTER: Chakravarthi VP

PROVIDER: S-EPMC7139164 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Transcriptome datasets of ESR2-regulated genes in rat granulosa cells during gonadotropin-induced follicle maturation.

Chakravarthi V Praveen VP Ghosh Subhra S Dai Eddie E Pathak Devansh D Rumi M A Karim MAK

Data in brief 20200310

Disruption of estrogen receptor beta (ESR2) dysregulates granulosa cell genes essential for follicle maturation and ovulation. The datasets presented in this article depict gonadotropin-induced genes, which are differentially expressed in <i>Esr2</i>-null rat granulosa cells. Synchronized follicle development was initiated in four-week-old wildtype and <i>Esr2</i>-null female rats by administration of PMSG. Forty-eight hours after PMSG injection, further maturation of ovarian follicles was induc ...[more]

PMID: 32280735

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Project description:BackgroundSuperovulation treatment had some adverse effects on maturity and development of oocytes. Can superovulation dose of gonadotropins (Gns) affect the transcriptome of granulosa cells and follicular fluid (FF) hormone levels?MethodsOne leading pre-ovulatory follicle per subject was used from three natural-cycle and four Gn-stimulated patients. Granulosa cells and FF samples were collected from the same leading follicle of each patient. RNA was extracted from granulosa cells and subjected to deep sequencing and analysis. Follicle-stimulating hormone (FSH), estradiol (E2), androstenedione (AND), testosterone (T), luteinizing hormone (LH), and progesterone (P4) levels in FF were measured by immunoassays. Student's t test was used for statistical analysis.ResultsA total of 715 genes were up-regulated, and 287 genes were down-regulated, in the Gn-stimulated group relative to the control group. Gene Ontology analysis revealed that the down-regulated genes were enriched in cell cycle and meiosis pathways, primarily those associated with follicle or oocyte maturation and quality. On the other hand, the up-regulated genes were enriched in functions related to immunity and cytokine-cytokine receptor interactions. Compared to the follicles of natural cycle, the E2 and LH concentrations were significantly reduced (P < 0.001), the P4 concentration was significantly increased (P = 0.003), and the concentrations of FSH, T and AND had no difference in the follicles of Gn-stimulated cycle.ConclusionsCell cycle- and meiosis-associated genes were down-regulated by Gns stimulation, whereas immune- and cytokine-associated genes were up-regulated. Hormone levels were also affected by Gns stimulation. Compared with natural-cycle follicles,putative markers associated with oocyte quality and follicle maturation were significantly different from those in Gn-stimulated follicles. Hormone levels in follicles were compatible with the steroidogenic patterns of granulosa cell, which reflects the follicle maturation and oocyte quality.

Project description:BackgroundCyanobacterial harmful algal blooms (CyanoHABs) originate from the excessive growth or bloom of cyanobacteria often referred to as blue-green algae. They have been on the rise globally in both marine and freshwaters in recently years with increasing frequency and severity owing to the rising temperature associated with climate change and increasing anthropogenic eutrophication from agricultural runoff and urbanization. Humans are at a great risk of exposure to toxins released from CyanoHABs through drinking water, food, and recreational activities, making CyanoHAB toxins a new class of contaminants of emerging concern.ObjectivesWe investigated the toxic effects and mechanisms of microcystin-LR (MC-LR), the most prevalent CyanoHAB toxin, on the ovary and associated reproductive functions.MethodsMouse models with either chronic daily oral or acute intraperitoneal exposure, an engineered three-dimensional ovarian follicle culture system, and human primary ovarian granulosa cells were tested with MC-LR of various dose levels. Single-follicle RNA sequencing, reverse transcription-quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, western blotting, immunohistochemistry (IHC), and benchmark dose modeling were used to examine the effects of MC-LR on follicle maturation, hormone secretion, ovulation, and luteinization.ResultsMice exposed long term to low-dose MC-LR did not exhibit any differences in the kinetics of folliculogenesis, but they had significantly fewer corpora lutea compared with control mice. Superovulation models further showed that mice exposed to MC-LR during the follicle maturation window had significantly fewer ovulated oocytes. IHC results revealed ovarian distribution of MC-LR, and mice exposed to MC-LR had significantly lower expression of key follicle maturation mediators. Mechanistically, in both murine and human granulosa cells exposed to MC-LR, there was reduced protein phosphatase 1 (PP1) activity, disrupted PP1-mediated PI3K/AKT/FOXO1 signaling, and less expression of follicle maturation-related genes.DiscussionUsing both in vivo and in vitro murine and human model systems, we provide data suggesting that environmentally relevant exposure to the CyanoHAB toxin MC-LR interfered with gonadotropin-dependent follicle maturation and ovulation. We conclude that MC-LR may pose a nonnegligible risk to women's reproductive health by heightening the probability of irregular menstrual cycles and infertility related to ovulatory disorders. https://doi.org/10.1289/EHP12034.

Dataset Information

Transcriptome datasets of ESR2-regulated genes in rat granulosa cells during gonadotropin-induced follicle maturation.

Publications

Transcriptome datasets of ESR2-regulated genes in rat granulosa cells during gonadotropin-induced follicle maturation.

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