Ovarian Development Research Articles

Seven up regulates reproductive diapause initiation via juvenile hormone biosynthesis in the cabbage beetle Colaphellus bowringi

AbstractReproductive diapause is an insect survival strategy in which reproduction temporarily halts in response to adverse environmental changes. This process is characterized by arrested ovarian development and lipid accumulation in females. A reduction in juvenile hormone (JH) biosynthesis is known to initiate reproductive diapause, but its regulatory mechanism remains unclear. Seven up (Svp), a transcription factor from the nuclear receptor family, plays a crucial role in various developmental processes in insects. In this study, using the cabbage beetle Colaphellus bowringi as a model, we observed higher expression of Svp in the heads of female adults under reproductive photoperiodic conditions (short‐day [SD]) compared to diapause conditions (long‐day [LD]). RNA interference‐mediated knockdown of Svp in SD females induced typical diapause phenotypes, including ovarian arrest and lipid accumulation. The application of methoprene (ME), a JH receptor agonist, reversed these diapause phenotypes and restored reproduction, indicating that Svp’s regulation of reproductive diapause is dependent on JH signaling. Additionally, Svp knockdown led to the downregulation of JH pathway genes and a reduction in JH titers. Further evidence suggested that Svp regulates the expression of JHAMT1, a critical gene in JH biosynthesis, which determines diapause entry in C. bowringi. These findings suggest that diapause‐inducing photoperiods suppress Svp expression, blocking JH production and triggering diapause. This work reveals a critical transcription factor that regulates reproductive diapause initiation through modulating JH production, providing a potential target for controlling pests capable of entering reproductive diapause.

High Frequency of PIK3R1 Alterations in Ovarian Cancers: Clinicopathological and Molecular Associations

Background: The phosphoinositide 3-kinase (PI3K) pathway is activated in multiple cancers. However, the significance of PIK3R1 encoding the PI3K regulatory subunit, an inhibitor of the PI3K catalytic subunit encoded by PIK3CA, in ovarian cancer development is largely unknown. Methods: Here, we investigated PIK3R1 genomic alterations and gene expression by direct sequencing and qPCR methods in 197 ovarian cancers. The results were correlated with clinicopathological and molecular variables and patient outcomes. Results: In addition to mutations (3.5%) and allelic losses (28.4%), we observed a very high frequency of decreased PIK3R1 mRNA levels in ovarian carcinomas (95.8%). Tumors with PIK3R1 mutations mostly represented low-stage cancers of endometrioid and clear-cell type. Tumors with PIK3R1 deletion and underexpression shared similar phenotypes of high-grade carcinomas (p = 0.003 and p = 0.025, respectively). Allelic loss was also associated with advanced stages (p = 0.003) and high-grade serous histotypes (p = 0.004). The PIK3R1 copy number correlated with mRNA levels (p = 0.009). PIK3R1 mutations coexisted with PTEN mutations (p = 0.041), whereas PIK3R1 deletion and underexpression were linked to PIK3CA amplification (p = 0.038 and p = 0.033, respectively). Low PIK3R1 expression diminished the probability of a complete response (OR 0.07, p = 0.03) in patients treated with platinum-based regimens. Conclusions: PIK3R1 alterations may contribute to the development of ovarian cancers with different malignant potential and molecular changes. The high frequency of PIK3R1 aberrations suggests their importance in PI3K pathway deregulation, and they may potentially serve as an alternative to PIK3CA markers for therapy with these pathway inhibitors.

Hairy and Krüppel homolog 1 Comediate the Action of Juvenile Hormone/Methoprene-Tolerant Signaling Pathway in Vitellogenesis of Spodoptera frugiperda (J.E. Smith).

Spodoptera frugiperda is a major migratory invasive pest and is of global concern. Vitellogenesis, a crucial process for population multiplication in oviparous insects, is regulated by endocrine hormones. In this study, three primary responders to JH signaling, the JH receptor gene Met, and the downstream transcription factor Kr-h1 and Hairy, were first cloned and identified. RNA interference results showed that silencing SfMet significantly down-regulated the transcription levels of SfKr-h1 and SfHairy, as well as the key reproductive genes Vitellogenin (SfVg) and Vitellogenin receptor (SfVgR). Similarly, silencing SfKr-h1 and SfHairy also inhibited the transcription of SfVg and SfVgR. Silencing of SfMet, SfKr-h1, and SfHairy genes resulted in blocked ovarian development and a significant decrease in reproduction. These findings confirm that Hairy and Kr-h1 comediate the action of the JH-Met signaling pathway in vitellogenesis of S. frugiperda, providing new targets and insights for pest control.

A targetable OSGIN1 − AMPK − SLC2A3 axis controls the vulnerability of ovarian cancer to ferroptosis

Despite advances in various chemotherapy regimens, current therapeutic options are limited for ovarian cancer patients. Oxidative stress-induced growth inhibitor 1 (OSGIN1), which is a tumor suppressor gene known to regulate the cellular stress response and apoptosis, is associated with ovarian cancer development. However, the underlying mechanisms involved in ferroptosis regulation have not been elucidated. Thus, this study aimed to investigate the effect and underlying regulatory mechanism of the OSGIN1 gene on ovarian cancer cells. Our results demonstrated that loss of the OSGIN1 gene promoted ovarian cancer growth and conferred resistance to drug-induced ferroptosis. Mechanistically, the loss of OSGIN1 activates AMPK signaling through ATM, leading to the upregulation of SLC2A3, which protects cells from ferroptosis and renders them insensitive to ferroptosis inducers. Notably, an SLC2A3-neutralizing antibody enhances the ferroptosis-inducing and anticancer effects of sorafenib on ovarian cancer patient-derived xenograft tumors. Overall, anti-SLC2A3 therapy is a promising method to improve ovarian cancer treatment by targeting ferroptosis.

Morphological and histochemical characteristics of the foregut, midgut, and hindgut, and their alterations during ovarian development in female freshwater prawn, Macrobrachium rosenbergii.

The anatomical, histological, and histochemical characteristics of the foregut (FG), midgut (MG), and hindgut (HG), as well as their alterations during the ovarian cycle in female prawns, Macrobrachium rosenbergii, were investigated. The esophagus (ESO), cardia (CD), and pylorus (PY) are the main components of the FG. An epithelium (Ep) with thick cuticle (Cu) layers lining the ESO, and the ESO is encircled by the ESO glands. The CD has a thick musculature, whereas the Ep of the PY are characterized by numerous villi andcolumnar Ep cells with a thinner layer of Cu. The inner longitudinal (LM)and the outer circular (CM)muscles were both present in the PY. The MG is lined by Ep cells which are connected to the basement membrane, and it lacks Cu. Microvilli, and subapical vacuoles are visible on the apical surface of Ep cells of the MG. The outermost layer is characterized by a dense stripof elastic fibers and a cluster of collagen fibers. The HG has the Ep cells with a thin Cu layer, and the HG glands form a rosette-like structure. The HG is surrounded by the CM and the LM fibers. The reactivities of Periodic Acid Schiff and Alcian Blue in these digestive organs altered throughout the ovarian cycle, and this was supported by the increased expression of mucin levels as ovarian maturation progressed. Our results offer novel and significant insights into the anatomical and histochemical structures of these digestive organs, and demonstrate a significant correlationbetween ovarian development and feeding in the female prawn, M. rosenbergii.

Long non-coding RNA NEAT1 promotes ovarian granulosa cell proliferation and cell cycle progression via the miR-29a-3p/IGF1 axis

BackgroundGranulosa cell proliferation and survival are essential for normal ovarian function and follicular development. Long non-coding RNAs (lncRNAs) have emerged as important regulators of cell proliferation and differentiation. Nuclear paraspeckle assembly transcript 1 (NEAT1) has been implicated in various cellular processes, but its role in granulosa cell function remains unclear.MethodsWe investigated the function of lncRNA NEAT1 in human ovarian granulosa-like tumor cells (KGN). The effects of NEAT1 overexpression or silencing on cell proliferation and cell cycle were evaluated using CCK-8 assays and flow cytometry. The interaction between NEAT1, miR-29a-3p, and IGF1 was examined using dual-luciferase reporter assays, qRT-PCR, and Western blot analysis.ResultsNEAT1 promoted granulosa cell proliferation and cell cycle progression by indirectly upregulated IGF1 expression through acting as a molecular sponge for miR-29a-3p. Cell proliferation and G2/M phase proportions were increased by overexpression of NEAT1, whereas cell proliferation and G2/M phase proportions decreased with NEAT1 silencing. The effects of NEAT1 on cell proliferation and cell cycle-related proteins (CCNB1 and CDK2) were partially reversed by miR-29a-3p mimic, while miR-29a-3p inhibitor rescued the effects of NEAT1 silencing.ConclusionLncRNA NEAT1 could promote ovarian granulosa cell proliferation and cell cycle progression via the miR-29a-3p/IGF1 axis in polycystic ovary syndrome. Further investigation of this mechanism in clinical samples may have implications for understanding ovarian physiology and pathology.

The piRNA protein Asz1 is essential for germ cell and gonad development in zebrafish and exhibits differential necessities in distinct types of germ granules.

Germ cells are essential for fertility, embryogenesis, and reproduction. Germline development requires distinct types of germ granules, which contains RNA-protein (RNP) complexes, including germ plasm in embryos, piRNA granules in gonadal germ cells, and the Balbiani body (Bb) in oocytes. However, the regulation of RNP assemblies in zebrafish germline development are still poorly understood. Asz1 is a piRNA protein in Drosophila and mice. Zebrafish Asz1 localizes to both piRNA and Bb granules, with yet unknown functions. Here, we hypothesized that Asz1 functions in germ granules and germline development in zebrafish. We generated asz1 mutant fish to determine the roles of Asz1 in germ cell development. We show that Asz1 is dispensable for somatic development, but essential for germ cell and gonad development. asz1-/- fish developed exclusively as sterile males with severely underdeveloped testes that lacked germ cells. In asz1 mutant juvenile gonads, germ cells undergo extensive apoptosis, demonstrating that Asz1 is essential for germ cell survival. Mechanistically, we provide evidence to conclude that zygotic Asz1 is not required for primordial germ cell specification or migration to the gonad, but is essential during post-embryonic gonad development, likely by suppressing the expression of germline transposons. Increased transposon expression and mis-organized piRNA granules in asz1 mutants, argue that zebrafish Asz1 functions in the piRNA pathway. We generated asz1;tp53 fish to partially rescue ovarian development, revealing that Asz1 is also essential for oogenesis. We further showed that in contrast with piRNA granules, Asz1 is dispensable for Bb granule formation, as shown by normal Bb localization of Buc and dazl. By uncovering Asz1 as an essential regulator of germ cell survival and gonadogenesis in zebrafish, and determining its differential necessity in distinct germ granule types, our work advances our understanding of the developmental genetics of reproduction and fertility, as well as of germ granule biology.

Adrenal hypoandrogenism in adolescents with premature ovarian insufficiency.

Premature ovarian insufficiency (POI) affects 1 in 10,000 children, with its molecular causes largely unknown. Adult studies suggest that low androgen levels induce ovarian insufficiency, but data on about this in children is limited. This study aims to assess the prevalence of low androgen levels in childhood POI and its relationship with adrenal insufficiency. Idiopathic POI adolescents were categorized into two groups based on DHEAS and total testosterone (TT) measured by chemiluminescence. Low androgen group (LAG) was defined using cut-offs according to Tanner pubarche staging. Demographic, clinical, and laboratory data were compared. Morning cortisol <7 mcg/dL and/or ACTH >96 or <5 pg/mL were planned to undergo ACTH stimulation testing, with a peak cortisol response <18 mcg/dL considered insufficient. Forty-three adolescents, mean age 15.5±1.3 years with a 46, XX karyotype, normal FMR1 mutation, FSH levels >40 mIU/mL, and low AMH levels were included. In 14 cases (37.8 %), DHEAS and TT were low. In the LAG, pubarche was absent in seven patients, and initial height SDS was significantly lower. Morning cortisol ranged from 7.9 to 23.5 mcg/dL, with an ACTH of 29.4±9.7 pg/mL. No differences in adrenal steroids or correlations between DHEAS and ACTH were observed. Diminished androgen levels are prevalent in children with idiopathic POI. The potential for this condition to increase the risk of adrenal insufficiency and its impact on secondary ovarian insufficiency remains unclear. This study, the first of its kind in children, underscores the potential role of genetic factors in zona reticularis and ovarian development.

Tyrosine phosphatase SHP2 accelerated ovarian cancer via modulating integrin/ E-Cadherin/ ZEB1 induced EMT

This article focusing on examining the function and further, molecular function of SHP2 in ovarian cancer (OC). For the molecular mechanism, bioinformatics was applied to study the specifically expressed genes in ovarian cancer ; the western blotting was applied to identify the EGF, p-SHP2, ZEB1, and E-Cadherin expressions in ovarian cancer tissue and pair adjacent tissue; then SKOV3 cells were treated with EGF and infected with E-Cadherin overexpression lentivirus, and then cells were treated with benzyl butyl phthalate and IRS-1 respectively. Detection of expression of p-SHP2, ZEB1, E-Cadherin, α3-integrin, p-Src, p-SMAD2, Snail, Slug and SKOV3 cells of migration and invasion abilities were detected using Western blot method and cell scratch assay and Transwell assay; Progression of ovarian cancer was detected using subcutaneous tumor transplantation assay in nude mice and HE staining method and immunocyto. The bioinformatics analysis results suggested that SHP2 is highly specifically expressed and E-Cadherin, which is low specifically expressed in ovarian cancer tissues, while EGF, p-SHP2 or ZEB1 are highly expressed and E-Cadherin is low expressed in ovarian cancer tissues; Overexpression of E-Cadherin could reduce the expressions of p-SHP2, ZEB1, α3-integrin, p-Src, p-SMAD2, Snail and Slug might has roles in alleviating the ovarian cancer development and decreasing the levels of p-SHP2 and ZEB1 in tumor samples. And E-Cadherin overexpression reduced the migration and invasion ability of SKOV3 cells. SHP2 tyrosine phosphatase enhances the ovarian cancer cells’ motility and invasiveness by upregulation of the integrin/E-Cadherin switch through ZEB1 signal.

CRISPR targeting of FOXL2 c.402C>G mutation reduces malignant phenotype in granulosa tumor cells and identifies anti-tumoral compounds.

Forkhead box L2 (FOXL2) encodes a transcription factor essential for sex determination, and ovary development and maintenance. Mutations in this gene are implicated in syndromes involving premature ovarian failure and granulosa cell tumors (GCTs). This rare cancer accounts for less than 5% of diagnosed ovarian cancers and is causally associated with the FOXL2 c.402C>G, p.C134W mutation in 97% of the adult cases (AGCTs). In this study, we employed CRISPR technology to specifically eliminate the FOXL2 c.402C>G mutation in granulosa tumor cells. Our results show that this Cas9-mediated strategy selectively targets the mutation without affecting the wild-type allele. Granulosa cells lacking FOXL2 c.402C>G exhibit a reduced malignant phenotype, with significant changes in cell proliferation and invasion. Furthermore, these modified cells are more susceptible to dasatinib and ketoconazole. Transcriptomic and proteomic analyses reveal that CRISPR-modified granulosa tumor cells shift their expression profiles towards a wild-type-like phenotype. Additionally, this altered expression signature has led to the identification of new compounds with antiproliferative and pro-apoptotic effects on granulosa tumor cells. Our findings demonstrate the potential of CRISPR technology for the specific targeting and elimination of a mutation causing GCTs, highlighting its therapeutic promise for treating this rare ovarian cancer.

Regulator of G protein signaling-1 facilitates ovarian cancer development by modulating NF-kB signal pathway

Regulator of G protein signaling 1 (RGS1) is known to be highly expressed in various tumors, but its specific effects and regulatory mechanism in ovarian cancer (OC) progression are not well understood. To delve into the tumor biology, a predictive risk model for OC was developed, incorporating RGS1, PRKG2, CD24, and ABCB1, with RGS1 exhibiting the strongest correlation. The model’s reliability and validity were confirmed through Kaplan-Meier analysis, receiver operating characteristic (ROC) curve, and principal component analysis (PCA). The risk score was validated as an independent indicator of overall survival, and a nomogram model was created to predict overall survival. Moreover, RGS1 expression was found to be up-regulated and associated with a poor prognosis in OC. Functional studies revealed that deleting RGS1 inhibited OC cell proliferation both in vitro and in vivo, while overexpression of RGS1 enhanced cell proliferation. Additionally, blocking the NF-kB pathway was shown to impede RGS1-induced proliferation, and overexpression of p65 partially reversed the effects of RGS1 deletion, promoting the tumorigenic properties of OC cells. These findings suggest that RGS1 could be a valuable biomarker for predicting prognosis and a potential novel therapeutic target for OC treatment.

Transcriptome and metabolome revealed the effects of hypoxic environment on ovarian development of Tibetan sheep

Many studies on the adaptability of Tibetan sheep to hypoxia have been reported, but little attention has been paid to the reproduction of Tibetan sheep living at an altitude of more than 4000 m. In this study, the ovaries of Alpine Merino sheep (AM) living in middle-high altitude areas (2500 m) and the ovaries of Gangba Tibetan sheep (GB) and Huoba Tibetan sheep (HB) living in ultra-high altitude areas (4400 m or more) were collected. Through morphological, transcriptomics and metabolomics, the effects of ultra-high altitude areas on Tibetan sheep ovarian development and the molecular mechanism of sheep's adaptability to ultra-high altitude environment were explored. The results showed that the number of granulosa cells in AM was significantly higher than that in GB and HB. The transcriptome revealed several genes related to follicular development, such as DAPL1, IGFBP1, C5, GPR12, STRA6, BMPER, etc., which were mainly enriched in related pathways such as cell growth and development. Through metabolomics analysis, it was found that the differential metabolites between the three groups of sheep were mainly lipids and lipid-like small molecules, such as Glycerol 3-Phosphate, PC (16: 0 / 18: 3 (9Z, 12Z, 15Z)), mainly enriched in lipid metabolism and other related pathways. The results of combined analysis showed that Tryptophan metabolism and Steroid hormone biosynthesis may have a significant effect on Tibetan sheep follicular development. Some genes (including HSD17B7, CYP11A1, CYP19, HSD3B1, CYP17, etc.) and some metabolites (including Cortisone, 2-Methoxyestrone, etc.) are enriched in these pathways, regulating ovarian and follicular development by affecting estrogen, progesterone, etc.. The results further revealed the molecular mechanism of Tibetan sheep to adapt to the ultra-high altitude environment and maintain normal ovarian and follicular development through the regulation of genes and metabolites.

Zinc finger protein rotund is essential for wings and ovarian development by regulating lipid homeostasis in Locusta migratoria.

Cys2-His2-type zinc finger (C2H2-ZF) proteins are involved in diverse biological processes. In insects, the wing and ovarian development is crucial for reproduction and evolution, yet the physiological roles of C2H2-ZF proteins in these processes remain underexplored. Here, RNA-seq analyses identified C2H2-ZF protein genes that were differentially expressed during wing formation in Locusta migratoria. Among these, the gene encoding a C2H2-ZF protein Rotund (Rn) was highly expressed in the wing pads of fourth- and fifth-instar nymphs. RNA interference mediated knockdown of LmRn in nymph stages resulted in pronounced abnormalities with curled wings and reduced wing area. LmRn knockdown led to reduced expression of lipid transport-related genes during wing morphogenesis, significantly decreased triglyceride (TG) level. In addition, we also find that LmRn knockdown impaired ovarian development and oocyte maturation in female adults, with decreased expression levels of lipid synthesis-related genes, and vitellogenin genes (VgA, and VgB) in the fat body. Meanwhile, the number of lipid droplets, TG content, and protein levels in the ovaries were significantly decreased after LmRn was silenced. Together, our findings reveal that LmRn is essential for wing and ovarian development by regulating lipid homeostasis in locusts, offering a potential target for insect pest management.

Single-Cell RNA Sequencing in Ovarian Cancer: Current Progress and Future Prospects.

Ovarian cancer is one of the most prevalent gynaecological malignancies. The rapid development of single-cell RNA sequencing (scRNA-seq) has allowed scientists to use this technique to study ovarian cancer development, heterogeneity, and tumour environment. Although multiple original research articles have reported the use of scRNA-seq in understanding ovarian cancer and how therapy resistance occurs, there is a lack of a comprehensive review that could summarize the findings from multiple studies. Therefore, this review aimed to fill this gap by comparing and summarizing the results from different studies that have used scRNA-seq in understanding ovarian cancer development, heterogeneity, tumour microenvironment, and treatment resistance. This review will begin with an overview of scRNA-seq workflow, followed by a discussion of various applications of scRNA-seq in studying ovarian cancer. Next, the limitations and future directions of scRNA-seq in ovarian cancer research will be presented.

Sex determination factor, a novel male-linked gene in the sea cucumber Apostichopus japonicus: Molecular characterization, expression patterns and effects of gene knockdown.

Apostichopus japonicus is a highly significant marine aquaculture species. Research findings have indicated that male sea cucumbers demonstrate a more rapid growth rate compared to females, underscoring the potential advantages of establishing an all-male population. In this study, we identified a specific protein-coding gene (ORFan) within a 4565bp male fragment and named it sex determination factor (sdf). The sdf transcript exhibited ubiquitous expression in various adult male tissues, along with dynamic expression patterns in the testis across different developmental stages. Notably, knockdown of the sdf gene through immersion of embryos in its specific vivo-morpholino oligomers (vivo-MO) resulted in significant changes in the expression levels of several sex-related genes including piwi1, vasa, foxl2, and DNMT3. Additionally, a transcriptomic analysis showed that sdf knockdown resulted in significant alterations in multiple biological processes encompassing various sex-related gene ontology terms such as male gonad development, ovarian follicle development, and steroidogenesis. These results provide a molecular foundation for comprehending ORFans in sea cucumbers while offering a valuable method for gene knockdown studies in echinoderms.

A novel DUF 3472 domain-containing fern protein impairs reproduction in Helicoverpa armigera

Helicoverpa armigera is a polyphagous field crop insect pest. It poses a major threat to economically important crops leading to significant financial losses globally. Given the escalating resistance cases against chemical and Bt-based insecticides, there is an urgent need to identify new molecules to control this insect through different modes of action.In this endeavour, we have isolated a new protein [named Msc42] efficacious to H. armigera from the fern Microsorum scolopendria. The protein has two domains of unknown function- DUF 5077 and DUF 3472. At an LC50 of 3.6 μg/g, Msc42 severely impairs molting and metamorphosis in surviving larvae. Mass spectrometric analysis of the total soluble protein of larvae identified altered regulatory proteins responsible for impaired insect growth and reproduction. This includes larval cuticle proteins and endocuticle structural glycoproteins. Storage proteins were either at lower levels or below the detection threshold. Vitellogenins were also found deficient. The microscopic study showed that the fern protein ravaged ovarian follicle development leading to complete reproductive failure. Our results indicate that the novel fern protein Msc42 may offer an alternative strategy for controlling H. armigera.

Gga-miR-6634-5p Affects the proliferation and steroid hormone secretion of chicken (Gallus Gallus) granulosa cells by targeting MMP16.

MiRNAs are typically reported to play a negative regulatory role in post-transcriptional expression of target genes and are widely involved in a variety of biological processes such as growth, metabolism and reproduction. However, research on the role of miRNAs in the ovulation process of chicken ovaries is still insufficient compared to that in mammals. Here, we investigated the regulatory mechanisms of gga-miR-6634-5p in the growth and steroid hormone secretion of chicken granulosa cells (GCs) by targeting MMP16. We found that gga-miR-6634-5p significantly down-regulated the mRNA levels of proliferation-related genes (CCND1, CDK1, and CDK6), decreased cell viability, the number of EdU-labelled positive cells, and the percentage of S-phase cells, as analysed by quantitative real time PCR (qRT-PCR), cell counting kit-8 (CCK-8), 5-ethynyl-2'deoxyuridine (EdU) and flow cytometry analyses (P < 0.01 or P < 0.05). qRT-PCR and enzyme-linked immunosorbent assay (ELISA) results demonstrated that gga-miR-6634-5p up-regulated the expression of steroid synthesis-related genes (CYP19A1, 3β-HSD, StAR and FSHR) (P < 0.01 or P < 0.05), as well as the secretion of estradiol (E2) and progesterone (P4) (P < 0.01 or P < 0.05). Furthermore, we found that MMP16 protein and gene expression can be down-regulated by gga-miR-6634-5p and demonstrated that MMP16 is a target gene of gga-miR-6634-5p by dual luciferase reporter assay (P < 0.05). In addition, we found that MMP16 stimulated the proliferation of GCs, significantly inhibited the expression of steroid synthesis related genes (CYP19A1, StAR, 3β-HSD and FSHR), and decreased the secretion of E2 and P4 (P < 0.01 or P < 0.05), which was consistent with the inhibitory effect of gga-miR-6634-5p. It was further found by functional enrichment analysis, qRT-PCR, western blot (WB) and ELISA that MMP16 may play a regulatory role in GCs proliferation as well as steroid hormone secretion through the mTOR signaling pathway and PPAR signaling pathway. Therefore, this study demonstrates that gga-miR-6634-5p modulates the proliferation of chicken GCs and the secretion of steroid hormones by targeting MMP16, which may contribute to a better understanding of the functional mechanisms of miRNAs in the ovarian development of laying hens.

R-spondin1 plays an indispensable role in ovarian development of Qi River crucian carp (Carassius auratus) by regulating estrogen synthesis

R-spondin1 plays an indispensable role in ovarian development of Qi River crucian carp (Carassius auratus) by regulating estrogen synthesis

Epigenetic Modulation of Estrogen Receptor Signaling in Ovarian Cancer.

Ovarian cancer remains one of the leading causes of cancer-related deaths in women. There are several processes that are described to have a causal relationship in ovarian cancer development, progression, and metastasis formation, that occur both at the genetic and epigenetic level. One of the mechanisms involved in its pathogenesis and progression is estrogen signaling. Estrogen receptors (ER) α, ERβ, and G-protein coupled estrogen receptor 1 (GPER1), in concert with various coregulators and pioneer transcription factors, mediate the effects of estrogens primarily by the transcriptional regulation of estrogen responsive genes, thereby exerting pleiotropic effects including the regulation of cellular proliferation and apoptosis. The expression and activity of estrogen receptors and their coregulators have been demonstrated to be regulated by epigenetic mechanisms like histone modifications and DNA methylation. Here, we intend to summarize and to provide an update on the current understanding of epigenetic mechanisms regulating estrogen signaling and their role in ovarian cancer. For this purpose, we reviewed publications on this topic listed in the PubMed database. Finally, we assess to which extent drugs acting on the epigenetic level might be suitable for the treatment of ovarian cancer.

The satiety hormone cholecystokinin gates reproduction in fish by controlling gonadotropin secretion

Life histories of oviparous species dictate high metabolic investment in the process of gonadal development leading to ovulation. In vertebrates, these two distinct processes are controlled by the gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH), respectively. While it was suggested that a common secretagogue, gonadotropin-releasing hormone (GnRH), oversees both functions, the generation of loss-of-function fish challenged this view. Here, we reveal that the satiety hormone cholecystokinin (CCK) is the primary regulator of this axis in zebrafish. We found that FSH cells express a CCK receptor, and our findings demonstrate that mutating this receptor results in a severe hindrance to ovarian development. Additionally, it causes a complete shutdown of both gonadotropins secretion. Using in-vivo and ex-vivo calcium imaging of gonadotrophs, we show that GnRH predominantly activates LH cells, whereas FSH cells respond to CCK stimulation, designating CCK as the bona fide FSH secretagogue. These findings indicate that the control of gametogenesis in fish was placed under different neural circuits, that are gated by CCK.