Melatonin significantly down-regulates long non-coding RNA Cox2 in M1 macrophages stimulated with LPS

Dohyeong Kim,Haengseok Song 한국실험동물학회 2022 한국실험동물학회 학술발표대회 논문집 Vol.2022 No.7

자궁 내 배아 착상 환경에 대한 이해

송행석,Song, Haengseok 대한생식의학회 2006 Clinical and Experimental Reproductive Medicine Vol.33 No.3

Transcriptional profiling with a pathway-oriented analysis identifies dysregulated molecular phenotypes in the endometrium of patients with polycystic ovary syndrome.

Kim, Jin Yeong,Song, Haengseok,Kim, Hyunjoo,Kang, Hee Jung,Jun, Jin Hyun,Hong, Sung Ran,Koong, Mi Kyoung,Kim, In Sun Issued for the Endocrine Society by the Williams W 2009 The Journal of clinical endocrinology & metabolism Vol.94 No.4

<P>CONTEXT: Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by chronic oligo/anovulation, hyperandrogenemia, infertility, and metabolic alterations related to insulin resistance. These abnormalities in PCOS may have complex effects on pathophysiology of the endometrium, contributing to infertility and endometrial disorders. OBJECTIVE: The objective of this study was to examine dysregulated signaling pathways in the endometrium of patients with PCOS (PCOSE) by analyzing expression profiles with a pathway-oriented method. DESIGN: Microarrays, RT-PCR, laser capture microdissection, and immunohistochemistry were performed with endometrial tissues. SETTING: This study was performed at a university hospital laboratory. Patients: This study comprised 12 regularly cycling women and 12 PCOS patients. MAIN OUTCOME MEASURE: Dysregulated signaling pathways in PCOSE were identified as a gene set. RESULTS: Hierarchical clustering revealed distinct expression profiles for PCOSE and the endometrium of normal cycling women. Gene sets associated with androgen signaling were not enriched in PCOSE, although they affect ovarian physiology of PCOS patients. Several biological pathways including cell cycle, apoptosis, glycolysis, and integrin-Rho-cytoskeleton network were aberrantly down-regulated in PCOSE. Expression of genes constituting these gene sets enriched in normal cycling women was systemically down-regulated in PCOSE. Laser capture microdissection-coupled real-time RT-PCR and immunohistochemistry further demonstrated that cell proliferation in the stroma, but not the epithelium, is significantly reduced in PCOSE. CONCLUSIONS: Systemic down-regulation of various signaling pathways in PCOSE with extremely prolonged proliferative phase provides insight into the abnormal phenotypes that reflect pathophysiology of PCOS in the endometrium, possibly leading to increased risks of endometrial disorders.</P>

Egr-1 is necessary for fibroblast growth factor-2-induced transcriptional activation of the glial cell line-derived neurotrophic factor in murine astrocytes.

Shin, Soon Young,Song, Haengseok,Kim, Chang Gun,Choi, Yang-Kyu,Lee, Kyoung Sun,Lee, Seung-Jae,Lee, He-Jin,Lim, Yoongho,Lee, Young Han American Society for Biochemistry and Molecular Bi 2009 The Journal of biological chemistry Vol.284 No.44

<P>Glial cell line-derived neurotrophic factor (Gdnf) promotes neurite outgrowth and survival of neuronal cells, but its transcriptional regulation is poorly understood. Here, we sought to investigate the mechanism underlying fibroblast growth factor-2 (FGF2) induction of Gdnf expression in astrocytes. We found that FGF2 stimulation of rat astrocytes induced expression of Egr-1 at a high level. Sequence analysis of the rat Gdnf gene identified three overlapping Egr-1-binding sites between positions -185 and -163 of the rat Gdnf promoter. Transfection studies using a series of deleted Gdnf promoters revealed that these Egr-1-binding sites are required for maximal activation of the Gdnf promoter by FGF2. Chromatin immunoprecipitation analysis indicated that Egr-1 binds to the Gdnf promoter. Furthermore, the induction of Gdnf expression by FGF2 is strongly attenuated both in C6 glioma cells stably expressing Egr-1-specific small interfering RNA and in primary cultured astrocytes from the Egr-1 knock-out mouse. Additionally, we found that stimulation of the ERK and JNK pathways by FGF2 is functionally linked to Gdnf expression through the induction of Egr-1. These data demonstrate that FGF2-induced Gdnf expression is mediated by the induction of Egr-1 through activation of the ERK and JNK/Elk-1 signaling pathways.</P>

Etv5, a transcription factor with versatile functions in male reproduction

Eo, Jinwon,Song, Haengseok,Lim, Hyunjung Jade The Korean Society for Reproductive Medicine 2012 Clinical and Experimental Reproductive Medicine Vol.39 No.2

Transcription factors govern diverse aspects of cell growth and differentiation as major switches of gene expression. Etv5, a member of the E26 transformation-specific family of transcription factors, has many stories to share when it comes to reproduction. Etv5 deficient mice show complex infertility phenotypes both in males and females. In males, the infertility phenotype exhibited by Etv5 deficiency is sexually dimorphic, and it involves both somatic cells and germ cells. In $Etv5^{-/-}$ female mice, the problem is more complicated by hormonal involvement. This review synthesizes old and new information on this versatile transcription factor-from the inadvertent discovery of its role in the testes to its newly discovered role in maintaining spermatogonial stem cells.

LncRNA PTPRE-AS1 expression is significantly increased in IL-4 induced M2 macrophages

Hye Jin Choi,Haengseok Song 한국실험동물학회 2022 한국실험동물학회 학술발표대회 논문집 Vol.2022 No.7

Evolving tales of autophagy in early reproductive events

Lim, Hyunjung J.,Song, Haengseok University of the Basque Country Press 2014 The International journal of developmental biology Vol.58 No.2

<P>Cells learn to thrive under unfavorable conditions by various mechanisms, and autophagy, self-eating, is one such mechanism. Autophagy is always ongoing in cells at a basal level to turn over old proteins, provide building blocks for new proteins, and to dispose of unnecessary byproducts of metabolism, and normally it does not cause deleterious effects on other parts of basic cellular processes. Autophagy is often dubbed a 'double-edged sword', as it is a necessary process for many cells, but its exaggeration may lead to cell death. Evidence is accumulating that autophagy is crucially involved in specific aspects of reproduction. Several recent studies have illustrated how the uniqueness of self-eating is manifested in germ cells and embryos. In this review, we attempt to portray where this relatively young field of autophagy research is heading in the context of reproductive biology research.</P>

Egr1 is a critical transcription factor to mediate estrogen responses in mouse uterus

Jung Ah Yoon,Haengseok Song 한국발생생물학회 2011 한국발생생물학회 학술발표대회 Vol.30 No.-

The Egr family of zinc finger transcription factors consisting of 4 members (Egr1 to Egr4) regulates critical genetic programs involved in cellular growth, differentiation, and function. They are co-ex-pressed in many different tissues, suggesting that they may have some redundant functions. While it is clear that estrogen regulates Egr1 in estrogen sensitive breast cancer cells, function of Egr1 and mechanisms by which estrogen (E2) and/or progesterone (P4) regulates Egr1 in uterus still remain unexplored. Thus, we have examined regulatory mechanisms by which Egr1 is regulated in the uterus and abnormal uterine phenotypes of Egr1(-/-) mice. Eight-week-old female mice were ovariectomized (OVX) and rested for a week. Uteri of OVX mice treated with various concentrations of E2 and/or other hormones were collected at 2 h after hormone treatment unless otherwise indicated. ICI 182,780 [estrogen receptor (ER) antagonist] or RU486 [progesterone receptor (PR) antagonist] was injected to OVX mice 30 min prior to hormone treatments. OVX Egr1(+/+) and Egr1(-/-) mice were treated with E2 and/or P4 to examine expression patterns of genes important for estrogen responses, and steroid hormone-induced cell proliferation in the uterus. Collected uteri were utilized for RT-PCR, realtime RT-PCR, Western blotting and histological analyses. Egr1 mRNA was rapidly induced with the highest level at 2h after E2 treatment and gradually deceased to basal levels at 12 h. Pretreatment of ICI 182,780 significantly reduced E2-induced increase of Egr1. However, an agonist for GPR30, a membrane estrogen receptor failed to induce mRNA expression of Egr1, suggesting that E2-dependent Egr1 transcription is mainly regulated via nuclear estrogen receptor, ER. P4 effectively dampened E2-dependent Egr1 transcription and its antagonistic effects were partially interfered with RU486 pretreatment. Histological analyses with BrdU incorporation experiments showed that vascular permeability (an early estrogen response) but not cell proliferation (a late response) was significantly impaired in the uteri of E2 treated OVX Egr1(-/-) mice. Interestingly, some genes involved in early estrogen responses such as Bip and HIF-1a but not those in late responses are dysregulated in uteri of Egr1(-/-) mice. Collectively, our results show that E2 transiently induces Egr1 via activation of nuclear ER. P4 antagonizes E2-dependent Egr1 regulation via PR. Impaired early estrogenic responses in Egr1(-/-) uteri could be due to aberrant gene expression affected by loss of Egr1 which act as a master regulator of estrogen actions in the uterus.-ex

Application of serum anti-Müllerian hormone levels in selecting patients with polycystic ovary syndrome for in vitro maturation treatment

Seok, Hyun Ha,Song, Haengseok,Lyu, Sang Woo,Kim, You Shin,Lee, Dong Ryul,Lee, Woo Sik,Yoon, Tae Ki The Korean Society for Reproductive Medicine 2016 Clinical and Experimental Reproductive Medicine Vol.43 No.2

Objective: The purpose of this study was to identify useful clinical factors for the identification of patients with polycystic ovary syndrome (PCOS) who would benefit from in vitro maturation (IVM) treatment without exhibiting compromised pregnancy outcomes. Methods: A retrospective cohort study was performed of 186 consecutive patients with PCOS who underwent human chorionic gonadotropin-primed IVM treatment between March 2010 and March 2014. Only the first IVM cycle of each patient was included in this study. A retrospective case-control study was subsequently conducted to compare pregnancy outcomes between IVM and conventional in vitro fertilization (IVF) cycles. Results: Through logistic regression analyses, we arrived at the novel finding that serum $anti-M{\ddot{u}}llerian$ hormone (AMH) levels and the number of fertilized oocytes in IVM were independent predictive factors for live birth with unstandardized coefficients of 0.078 (95% confidence interval [CI], 1.005-1.164; p=0.037) and 0.113 (95% CI, 1.038-1.208; p=0.003), respectively. Furthermore, these two parameters were able to discriminate patients who experienced live births from non-pregnant IVM patients using cut-off levels of 8.5 ng/mL and five fertilized oocytes, respectively. A subsequent retrospective case-control study of patients with PCOS who had serum AMH levels ${\geq}8.5ng/mL$ showed that IVM had pregnancy outcomes comparable to conventional IVF, and that no cases of ovarian hyperstimulation syndrome were observed. Conclusion: Serum AMH levels are a useful factor for predicting pregnancy outcomes in PCOS patients before the beginning of an IVM cycle. IVM may be an alternative to conventional IVF for PCOS patients if the patients are properly selected according to predictive factors such as serum AMH levels.

Preeclampsia leads to dysregulation of various signaling pathways in placenta

Kang, Jin Hee,Song, Haengseok,Yoon, Jung Ah,Park, Dong Yoon,Kim, Sung Han,Lee, Kyoung Jin,Farina, Antonio,Cho, Yeon Kyung,Kim, Young Nam,Park, Sang Won,Kim, Gi Jin,Shim, Sung Han,Cha, Dong Hyun Lippincott Williams Wilkins, Inc. 2011 Journal of Hypertension Vol.29 No.5

OBJECTIVES: To compare gene expression profiles of placentas from preeclamptic and normal pregnancies. STUDY DESIGN: We performed microarray experiments to analyze genome-wide expression profiling for 10 placentas from pregnant women with preeclampsia and 10 placentas from women who experienced noncomplicated pregnancies (CON), and to identify dysregulated signaling pathways as well as genes in preeclampsia. RT-PCR, real-time RT-PCR and/or immunofluorescence analyses were performed to validate the data obtained from microarray experiments. RESULTS: Unsupervised hierarchical clustering showed heterogeneity of preeclampsia at the molecular levels, whereas expression profiles of preeclampsia are distinctly different from those of CON. A list of genes which are differentially expressed between preeclampsia and CON included well known preeclampsia markers, such as Flt-1, leptin, HTRA1 and SIGLEC6. Gene Set Enrichment Analysis, a pathway-oriented analysis method for expression profiles, provided evidence that a number of biological activities including pathways that regulate actin cytoskeleton, TGF&bgr; signaling, oxidative phosphorylation, and proteasome activity were aberrantly either up-regulated or down-regulated in preeclampsia. RT-PCR and real-time-RT-PCR for genes contributing these biological pathways (gene sets) enriched in either CON or preeclampsia reinforced that these biological processes were systemically dysregulated in preeclampsia. CONCLUSIONS: Genome-wide expression profiles of preeclampsia showed heterogeneous characteristics of preeclampsia at the molecular levels. Dysregulation of genes and biological pathways could contribute to abnormal behavior of preeclmapsia. Our results will help further understand underlying mechanisms by which preeclampsia affects placental physiology.