Rina Meidan

Rina Meidan
Hebrew University of Jerusalem | HUJI · Department of Animal Sciences

PhD

About

153
Publications
21,627
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Introduction
Rina Meidan works at the Department of Animal Sciences, Hebrew University of Jerusalem. Her research in Reproductive Endocrinology is targeted mainly on corpus luteum. Her most recent publications are: 1. miR-210 and GPD1L regulate EDN2 in primary and immortalized human granulosa-lutein cells., doi: 10.1530/REP-17-0574. Epub 2018 Jan 4. 2.Fibroblast Growth Factor-2 and Transforming Growth Factor-beta1 Oppositely Regulate miR-221 that Targets Thrombospondin-1 in Bovine Luteal Endothelial Cells. doi: 10.1093/biolre/iox167. 3. Interferon-tau promotes luteal endothelial cell survival and inhibits specific luteolytic genes in bovine corpus luteum. doi: 10.1530/REP-17-0290. Epub 2017 Aug 14. PMID: 28808111

Publications

Publications (153)
Article
Full-text available
Background: Human granulosa-lutein cells (hGLCs) amply express sirtuin-1 (SIRT1), a NAD+-dependent deacetylase that is associated with various cellular functions. SIRT1 was shown to elevate cAMP on its own and additively with human chorionic gonadotropin (hCG), it is therefore interesting to examine if SIRT1 afects other essential hGLC functions. M...
Research
Full-text available
Recent Contributions from Women Scientists to Animal Endocrinology: Pregnancy and Lactation Edited by Christine Aurich, Laura Hernandez Last update 24 August 2021 The special issue aims at publishing a collection of excellent reviews focusing on the research fields of pregnancy and parturition in domestic animals. This SI should not only summarize...
Article
Full-text available
Abstract: Granulosa-lutein cells (GLCs) from PCOS women display reduced HIF-1α and EDN2 levels , suggesting their role in PCOS etiology. Here, we investigated the mechanisms involved in aberrant EDN2 expression in PCOS, and its association with HIF-1α. Various HIF-1α-dependent factors were studied in GLCs from PCOS and compared to normally ovulatin...
Article
The corpus luteum (CL) plays a vital role in regulating the reproductive cycle, fertility, and in maintaining pregnancy. Interferon-tau (IFNT) is the maternal recognition of a pregnancy signal in domestic ruminants; its uterine, paracrine actions, which extend the CL lifespan, are widely established. However, considerable evidence also suggests a d...
Article
Full-text available
Background Maintenance of the corpus luteum (CL) beyond the time of luteolysis is essential for establishing pregnancy. Identifying the distinct features of early pregnancy CL remains unresolved, hence we analyzed here the transcriptome of CL on day 18 pregnant (P) and non-pregnant (NP) cows using RNA-Seq. CL of P cows expressed ISGs, verifying exp...
Article
Full-text available
Abstract Background: Maintenance of the corpus luteum (CL) beyond the time of luteolysis is essential for establishing pregnancy. Identifying the distinct features of early pregnancy CL remains unresolved, hence we analyzed here the transcriptome of CL on day 18 pregnant (P) and non-pregnant (NP) cows using RNA-Seq. CL of P cows expressed ISGs, ve...
Article
Full-text available
Sirtuins (SIRTs) are NAD+-dependent deacetylases that regulate proliferation and cell death. In the human ovary, granulosa cells express sirtuin 1 (SIRT1), which has also been detected in human tumors derived from granulosa cells, i.e., granulosa cell tumors (GCTs), and in KGN cells. KGN cells are an established cellular model for the majority of G...
Presentation
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HSTalks series on reproduction
Article
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Endothelin-2 (EDN2) expression in granulosa cells was previously shown to be highly dependent on the hypoxic mediator, HIF1A. Here we investigated whether sirtuin-1 (SIRT1), by deacetylating HIF1A and class III histones, modulates EDN2 in human granulosa-lutein cells (hGLCs). We found that HIF1A was markedly suppressed in the presence of resveratro...
Article
Full-text available
Sirtuin-1 (SIRT1), a NAD+-dependent deacetylase, is present in the ovarian granulosa cells (GCs) of various species. This study examined the regulation of SIRT1 expression in human granulosa-lutein cells (hGLCs). Two different, structurally unrelated SIRT1 activators, SRT2104 and resveratrol, dose-and time-dependently enhanced SIRT1 (∼2-and 1.5-fol...
Preprint
Full-text available
23 Sirtuin-1 (SIRT1), a NAD+-dependent deacetylase, is present in the ovarian granulosa cells 24 (GCs) of various species. This study examined the regulation of SIRT1 expression in human 25 granulosa-lutein cells (hGLCs). Two different, structurally unrelated SIRT1 activators, SRT2104 26 and resveratrol, dose-and time-dependently enhanced SIRT1 (~2...
Preprint
Full-text available
Pentraxin 3 (PTX3), a multimeric glycoprotein, is implicated in various biological functions. PTX3 was shown to be elevated in the corpus luteum (CL) of early pregnant ewes; however, its role in sheep or other ruminants' CL during this reproductive stage or how it is regulated remain unknown. Here we explored the role of PTX3 and its relationship w...
Article
Full-text available
Pentraxin 3 (PTX3), a multimeric glycoprotein, is implicated in various biological functions. PTX3 was shown to be elevated in the corpus luteum (CL) of early pregnant ewes; however, its role in sheep or other ruminants’ CL during this reproductive stage or how it is regulated remain unknown. Here we explored the role of PTX3 and its relationship w...
Article
Objective: Sirtuin1 (SIRT1), an NAD+-dependent enzyme, affects diverse cellular processes. Yet the reproductive functions of SIRT1 remain unclear. The aim of the study was to reveal the regulation of SIRT1 expression and its roles in human granulosa-lutein cells (hGLCs). Methods: hGLCs were retrieved from women undergoing IVF during oocytes retriev...
Article
Full-text available
Interferon-tau (IFNT), serves as a signal to maintain the corpus luteum (CL) during early pregnancy in domestic ruminants. We investigated here whether IFNT directly affects the function of luteinized bovine granulosa cells (LGCs), a model for large-luteal cells. Recombinant ovine IFNT (roIFNT) induced the IFN-stimulated genes (ISGs; MX2, ISG15, an...
Research
Full-text available
Interferon-tau (IFNT), a multifunctional type I interferon, serves as a signal to maintain the corpus luteum (CL) during early pregnancy in domestic ruminants. Here we aimed to study whether IFNT directly affects the function of luteinized bovine granulosa cells (LGCs), used as a model for large luteal cells. Recombinant ovine IFNT (roIFNT) stimula...
Article
Full-text available
Summary The CL is a transient gland, which is only functional for 17-18 days in the cyclic cow or for up to 200 days in the pregnant cow. Regression of the CL is essential for normal cyclicity as it allows the development of a new ovulatory follicle, while prevention of luteolysis is necessary for the maintenance of pregnancy. Evidence accumulated...
Article
Full-text available
The multimodular matricellular protein thrombospondin-1 (THBS1) was among the first identified endogenous antiangiogenic molecules. Recent studies have shown THBS1-mediated suppression of angiogenesis and other critical activities for corpus luteum (CL) regression. THBS1 is specifically induced by prostaglandin F2alpha in mature CL undergoing regre...
Article
Full-text available
During the periovulatory period the profile of FGF2 coincides with elevated PGE2 levels. We investigated therefore whether PGE2 can directly stimulate FGF2 production in bovine granulosa cells and if so, which PTGER type and signaling cascades are involved. We found that PGE2 temporally stimulated FGF2. Accordingly, endoperoxide-synthase2-silenced...
Data
Enriched GO terms in the early (day 4) and mid-luteal (day 11) stages. (XLSX)
Data
Networks of differentially expressed genes (day 4 vs. 11). (XLSX)
Article
Full-text available
To unveil novel global changes associated with corpus luteum (CL) maturation, we analyzed transcriptome data for the bovine CL on days 4 and 11, representing the developing vs. mature gland. Our analyses revealed 681 differentially expressed genes (363 and 318 on day 4 and 11, respectively), with ≥2 fold change and FDR of <5%. Different gene ontolo...
Article
Full-text available
1 Endothelin-2 (EDN2), expressed at a narrow window during the periovulatory period, 2 critically affects ovulation and corpus luteum (CL) formation. LH (acting mainly via 3 cAMP) and hypoxia are implicated in CL formation; therefore, we aimed to elucidate 4 how these signals regulate EDN2 using human primary (hGLCs) and immortalized 5 (SVOG) granu...
Article
Full-text available
Thrombospondin-1 (THBS1) is an important mediator of corpus luteum (CL) regression. Highly induced during luteolysis, it acts as a natural anti-angiogenic, proapoptotic compound. THBS1 expression is regulated in bovine luteal endothelial cells (LECs) by fibroblast growth factor-2 (FGF2) and transforming growth factor-beta1 (TGFB1) acting in an oppo...
Chapter
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It is well established that in ruminants, and in other species with estrous cycles, luteal regression is stimulated by the episodic release of prostaglandin F2α (PGF2α) from the uterus, which reaches the corpus luteum (CL) through a countercurrent system between the uterine vein and the ovarian artery. Because of their luteolytic properties, PGF2α...
Article
Full-text available
1 Interferon-tau (IFNT), a maternal recognition of pregnancy signals produced in domestic 2 ruminants, acts on uterine epithelium to suppress the release of luteolytic pulses of 3 prostaglandin F2a (PGF2a), thus extending the corpus luteum (CL) life span. However, it 4 is unknown whether it also exerts anti-luteolytic actions in CL. To examine the...
Conference Paper
Full-text available
Interferon-tau (IFNT) is a multifunctional cytokine that acts via Type-1 interferon signaling pathway and exhibits similar biological activity to other Type-1 interferons. In farm animals, the mononuclear trophectoderm of the conceptus secretes IFNT into the uterine lumen, during the peri-implantation period. Production of IFNT disrupts uterine rel...
Article
Full-text available
Running title: Regulation of miR-221 targeting thrombospondin-1 Summary sentence: Dynamic regulation of miR-221 throughout the cycle, affecting THBS1 and subsequently SERPINE1, can modulate vascular function in the corpus luteum. Abstract Thrombospondin-1 (THBS1) is an important mediator of corpus luteum (CL) regression. Highly induced during luteo...
Article
Full-text available
1 Endothelin-2 (EDN2), expressed at a narrow window during the periovulatory period, 2 critically affects ovulation and corpus luteum (CL) formation. LH (acting mainly via 3 cAMP) and hypoxia are implicated in CL formation; therefore, we aimed to elucidate 4 how these signals regulate EDN2 using human primary (hGLCs) and immortalized 5 (SVOG) granu...
Article
Full-text available
Introduction: FGF2 and thrombospondin-1 (THBS1) expression in corpus luteum (CL) exhibited the most divergent profile of induction by prostaglandin F2a (PGF2α). FGF2, a potent angiogenic pro-survival factor was increased in the Day 4 CL. In contrast, the anti-angiogenic, apoptotic factors, THBS1, transforming growth factor beta 1 (TGFB1) and plasmi...
Presentation
Full-text available
Introduction: Hypoxia and Endothelin-2 (EDN2) peak simultaneously during early corpus luteum (CL) formation, suggesting causal relationship. Indeed, hypoxia inducible factor-1 alpha (HIF1A) is a strong stimulator of EDN2 in granulosa–lutein cells (GLCs). Knockout of EDN2 resulted in un-ruptured follicles that failed to develop into CL, suggesting t...
Book
This book describes the life cycle of a unique endocrine gland that is absolutely essential for the establishment and maintenance of pregnancy in all mammalian species. The corpus luteum is unique because it is formed and destroyed every (non-fertile) reproductive cycle. When fertilization occurs, the corpus luteum is rescued or maintained. The pro...
Article
Full-text available
Thrombospondin-1 (THBS1) and transforming growth factor-beta1 (TGFB1) are specifically up-regulated by prostaglandin F2alpha in mature corpus luteum (CL). This study examined the relationship between the expression of THBS1 and TGFB1 and the underlying mechanisms of their actions in luteal endothelial cells (ECs). TGFB1 stimulated SMAD2 phosphoryla...
Article
Full-text available
Renal endothelin-converting enzyme (ECE)-1 is induced in experimental diabetes and following radiocontrast administration, conditions characterized by renal hypoxia, hypoxia-inducible factor (HIF) stabilization, and enhanced endothelin synthesis. Here we tested whether ECE-1 might be a HIF-target gene in vitro and in vivo. ECE-1 transcription and e...
Article
Full-text available
Hypoxia-inducible factor 1 alpha (HIF1A) and endothelin 2 (EDN2) are transiently expressed during the same time window in the developing corpus luteum (CL). In this study, we sought to investigate the involvement of LH/cAMP, reactive oxygen species (ROS), and a hypoxia-mimetic compound (CoCl2) on HIF1A expression and how it affected EDN2 levels, us...
Article
Full-text available
Prostaglandin endoperoxide synthase 2 (PTGS2), tumor necrosis factor-alpha-induced protein-6 (TNFAIP6), pentraxin-3 (PTX3), epidermal growth factor like factors: amphiregulin (AREG) and epiregulin (EREG) are essential for successful ovulation. We compared here the induction of these ovulatory genes in bovine granulosa cells (GCs) in vivo (after LH...
Article
Full-text available
Previously we showed luteal stage-specific regulation of angiogenesis modulating factors by prostaglandin F2 alpha (PGF2a). Fibroblast growth factor 2 (FGF2) and thrombospondins (THBSs) exhibited the most divergent profile of induction by PGF2a. We therefore examined the transcriptional regulation and roles of THBSs in luteal cells and studied thei...
Article
Full-text available
The corpus luteum (CL) undergoes dramatic morphological and functional changes throughout its lifespan. It initially develops from cells that remain in the follicle following ovulation. Eventually the mature CL is composed of multiple, distinctive cell types including steroidogenic cells (small and large luteal cells) and other cell types (endothel...
Article
Full-text available
The bovine corpus luteum (CL) is a transient gland with a life span of only 18 days in the cyclic cow. Mechanisms controlling CL development and secretory function may involve factors produced both within and outside this gland. Although luteinizing hormone (LH) surge is the main trigger of ovulation and granulosa cells luteinization, many locally...
Article
Full-text available
The hypoxic microenvironment that occurs in fast-growing tissue such as the corpus luteum (CL) is a major contributor to its ability to survive via the induction of an intricate vascular network. Cellular responses to hypoxia are mediated by hypoxia-inducible factor-1 (HIF-1), an oxygen-regulated transcriptional activator. HIF-1, a heterodimer cons...
Article
Hypoxia-inducible factor 1a (HIF-1a) is a critical mediator of physiological responses to hypoxia. stabilized HIF-1a protein initiates transcription of target genes by binding and transactivation to the hypoxia response element (HRE), located in their promoter. However, not all hypoxia responses are HIF/HRE mediated. Hypoxia also plays pivotal role...
Article
The thrombospondins (TSPs) comprise a family of extracellular proteins that participate in cell-to-cell and cell-to-matrix communication. Thrombospondin −1 (TSP-1) is a large, trimeric multi-modular protein that can exert its activity through multiple mechanisms involving different active sequences in different domains. These domains include bindin...
Article
Full-text available
To examine the levels of endothelin system components in granulosa lutein cells (GLCs) of women with PCOS and compare them to normally ovulating women undergoing In Vitro Fertilization (IVF). Polycystic ovary syndrome (PCOS) is one of the most common endocrine-metabolic disorders in women of reproductive age. Endothelins are locally produced by end...
Article
Full-text available
The ovary is a dynamic organ that undergoes cyclic structural and functional changes. Structurally, the internal architecture of the ovary constantly changes as follicles grow, rupture and transform into corpora lutea in a cyclical manner. Functionally, a variety of regulatory ovarian hormones are sequentially produced, and eggs are periodically re...
Article
Prostaglandin F(2α) (PGF(2α)) induces luteolysis via a specific receptor, PTGFR. Although PTGFR mRNA expression in the bovine corpus luteum (CL) has been studied previously, changes in PTGFR protein and its localization are not fully understood during the life span of the CL. In addition to full-length PTGFR, several types of PTGFR isoforms, such a...
Article
Full-text available
We recently compared prostaglandin F2alpha (PG)-induced global gene expression profiles in PG-refractory, bovine corpus luteum (CL) collected on Day 4 of the estrous cycle, versus PG-responsive, Day 11 CL. Transcriptome analyses led us to study the regulation of angiogenesis-related genes by PG and their functions in luteal endothelial cells (ECs)....
Data
Structural superposition of the PKR1 model and GPCR X-ray templates used for homology modeling. All structures are shown in ribbon representation. PKR1 is in turquoise, human β2-adrenergic is in orange (A), bovine rhodopsin is in gold (B) and human A2A-adenosine receptor is in gray (C). (D) Superposition of the hPKR1 model and the β2-adrenergic rec...
Data
Structures of the three known PKR antagonists that were used as reference compounds for constructing ligand-based pharmacophore models. (TIF)
Data
Ligand RMSD values and contact analysis for cognate ligand docking to β1adr and β2adr crystal structures and homology models. (DOC)
Data
Structural superposition of human PKR1 and PKR2 models. Both structures are shown in ribbon representation, with hPKR1 in turquoise and hPKR2 in khaki. The insert shows a detailed view of the predicted transmembrane binding site, with side chains denoted as sticks. Structural superposition was performed using the Matchmaker module in UCFS Chimera v...
Data
Structure-based multiple sequence alignment of modeled PKR subtypes and X-ray structures used as templates in the modeling procedure. Alignment was generated by the TCoffee server. The most conserved residue in each helix is shaded yellow and is indicated by its Ballesteros-Weinstein numbering [33]. Identical residues are in red and similar residue...
Data
Structural similarity between the identified VLS hits plotted as a heatmap. The degree of similarity was calculated using the Tanimoto coefficient, as described in Methods, and ranges between 0 (completely dissimilar compounds) and 1 (identical compounds). Compounds with similarity values >0.85 are usually considered structurally similar. Color int...
Data
Measure of Ka/Ks ratio on the amino acid sequence of the PKR subtypes suggests positive selection acting only on PKR2. Ka/Ks ratio (ω) representing the ratio of non-synonymous (Ka) to synonymous (Ks) nucleotide substitution rates was calculated for each site for the PKR subtypes. The ratio is plotted against the amino acid position for hPKR1 (A) an...
Data
Predicted binding modes of cognate ligands redocked into crystal structures and homology models. (A) Cyanopindolol redocked to β1adr crystal structure (PDB code: 2VT4), (B) Carazolol redocked to β1adr crystal structure (2YCW), (C) Carazolol redocked to β2adr crystal structure (2RH1), (D) Cyanopindolol docked to β1adr homology model, (E) Carazolol d...
Data
Potential hits identified from the ZINC database. (DOC)
Article
Full-text available
Background and Motivation The Prokineticin receptor (PKR) 1 and 2 subtypes are novel members of family A GPCRs, which exhibit an unusually high degree of sequence similarity. Prokineticins (PKs), their cognate ligands, are small secreted proteins of ∼80 amino acids; however, non-peptidic low-molecular weight antagonists have also been identified. P...
Article
This study compared immediate and carryover effects of mastitis induced by Gram-negative endotoxin (E. coli LPS) and Gram-positive exosecretions (Staph. aureus ex.) on preovulatory follicle function. Synchronized, uninfected cyclic lactating Holstein cows were treated with PGF(2α) on day 6 of the cycle and 36 h later, a dose of either E. coli LPS (...
Article
Chronic, subclinical intramammary infection depresses fertility. We previously found that 30% of subclinical mastitic cows exhibit delayed ovulation, low circulating estradiol levels, and delayed luteinizing hormone surge. We examined the function of preovulatory follicles of cows experiencing subclinical mastitis or a past event of acute clinical...
Article
Full-text available
The objective of this study was to identify prostaglandin F(2α) (PG)-induced changes in the transcriptome of bovine corpora lutea (CL) that are specific to mature, PG-responsive (day 11) CL vs. developing (day 4) CL, which do not undergo luteolysis in response to PG administration. CL were collected at 0, 4, and 24 h after PG injection on days 4 an...
Article
Full-text available
The pattern and regulation of endothlin-2 (EDN2) expression and its putative roles in bovine ovaries were investigated. EDN2 mRNA was determined in corpus luteum (CL) and during folliculoluteal transition induced by GnRH in vivo. EDN2 was elevated only in the early CL and was not present in older CL. In the young CL, EDN2 mRNA was identified mainly...