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Cell Research 1997年第2期7卷 179-193页

作者： VIVIA CT LIANG TIFFANY SEDGWICK YUN BOSHI(Laboratory of Molecular Embryology nichd/nih, Bldg.18T, Rm. 106 Bethesda, MD 20892-5431 USA) Laboratory of Molecular Embryology nichd/nih Bldg. 18T Rm. 106 Bethesda MD 20892-5431 USA

The complex transformation of a tadpole to a frogduring amphibian development is under the control of thyroid hormone (T3). T3 is known to regulate gene transcription through its nuclear receptors. We have previouslyisolated many genes which are up-regulated by T3 in theintestine of Xenopus laevis tadpoles. We have now cloneda full- length cDNA for one such gene (IU12). Sequenceanalysis shows that the IU12 cDNA encodes a plasmamembrane protein with 12 transmembrane domains andhomologous to a mammalian gene associated with cell activation and organ development. Similarly, we have foundthat IU12 is activated during intestinal remodeling whenboth cell death and proliferation take place. Furthermore,IU12 is an early T3-response gene and its expression in theintestine during T3-induced metamorphosis mimics thatduring normal development. These results argue for a roleof IU12 in the signal transduction pathways leading to intestinal metamorphosis.

关键词： Thyroid hormone Xenopus laevis cell proliferation organogenesis transcription factor

Role of the histone methyltransferases Ezh2 and Suv4-20h1/Suv4-20h2 in neurogenesis

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Neural Regeneration Research 2023年第3期18卷 469-473页

作者： Christopher T.Rhodes Chin-Hsing Annie Lin Eunice Kennedy Shriver National Institute of Child Health and Human Development(nichd) National Institutes of Health(NIH)BethesdaMDUSA Department of Integrative Biology University of Texas at San AntonioSan AntonioTXUSA University of Texas at San Antonio Neurosciences Institute San AntonioTXUSA

Mechanisms regulating neurogenesis involve broad and complex processes that represent intriguing therapeutic targets in the field of regenerative *** influential factor guiding neural stem cell proliferation and cellular differentiation during neurogenesis are epigenetic *** present an overview of epigenetic mechanisms including chromatin structure and histone modifications;and discuss novel roles of two histone modifiers,Ezh2 and Suv4-20h1/Suv4-20h2(collectively referred to as Suv4-20h),in neurodevelopment and *** review will focus on broadly reviewing epigenetic regulatory components,the roles of epigenetic components during neurogenesis,and potential applications in regenerative medicine.

关键词： adult neurogenesis epigenetic Ezh2 histone co-regulation histone modification neurodevelopment neurogenesis regenerative medicine Suv4-20h

Immune cells in term and preterm labor

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Cellular & Molecular Immunology 2014年第6期11卷 571-581页

作者： Nardhy Gomez-Lopez Derek StLouis Marcus A Lehr Elly N Sanchez-Rodriguez Marcia Arenas-Hernandez Department of Obstetrics & Gynecology and Immunology & Microbiology Wayne State University Detroit MI USA Perinatology Research Branch nichd/nih School of Medicine Wayne State University Detroit MI USA

Labor resembles an inflammatory response that includes secretion of cytokines/chemokines by resident and infiltrating immune cells into reproductive tissues and the maternal/fetal interface. Untimely activation of these inflammatory pathways leads to preterm labor, which can result in preterm birth. Preterm birth is a major determinant of neonatal mortality and morbidity; therefore, the elucidation of the process of labor at a cellular and molecular level is essential for understanding the pathophysiology of preterm labor. Here, we summarize the role of innate and adaptive immune cells in the physiological or pathological activation of labor. We review published literature regarding the role of innate and adaptive immune cells in the cervix, myometrium, fetal membranes, decidua and the fetus in late pregnancy and labor at term and preterm. Accumulating evidence suggests that innate immune cells （neutrophils, macrophages and mast cells） mediate the process of labor by releasing pro-inflammatory factors such as cytokines, chemokines and matrix metalloproteinases. Adaptive immune cells （T-cell subsets and B cells） participate in the maintenance of fetomaternal tolerance during pregnancy, and an alteration in their function or abundance may lead to labor at term or preterm. Also, immune cells that bridge the innate and adaptive immune systems （natural killer T （NKT） cells and dendritic cells （DCs）） seem to participate in the pathophysiology of preterm labor. In conclusion, a balance between innate and adaptive immune cells is required in order to sustain pregnancy; an alteration of this balance will lead to labor at term or preterm.

关键词： B cells cytotoxic T cells dendritic cells macrophages mast cells neutrophils NKT cells parturition preterm delivery regulatory T cells T cells

Understanding the impact of stress on teleostean reproduction

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Aquaculture and Fisheries 2022年第5期7卷 553-561页

作者： Raju Murugananthkumar Cheni-Chery Sudhakumari Department of Animal Biology School of Life SciencesUniversity of HyderabadP.O.Central UniversityHyderabad500046India Section on Molecular endocrinology Division of Developmental BiologyEunice Kennedy Shriver National Institute of Child Health and Human Development(NICHD)National Institutes of Health(NIH)BethesdaMD20892-4510USA.

Fishes exert stress response in a various ways depending on the type of the *** stress responses are activated through a cascade mechanism stimulated by the stressor which involves the hypothalamus-hypophyseal-interrenal(HHI)axis,catecholamines(CA),and *** stress responses may positively impact the fish survival and reproduction,while continuous or prolonged stress causes adverse effects on the fish ***-releasing factor and adrenocorticotropic hormone are the principal hormones responsible for producing corticosteroids through the HHI *** acts differentially on the stress response as it helps at the early developmental stage;conversely,it impairs the gonadal *** have a critical role in maintaining body homeostasis and intermediary metabolism,and they also have a predominant role in reproductive *** hormones,few genetic and epigenetic factors have been identified to understand the molecular responses to stress however,genome-wide associated studies will be initiated to investigate a complete picture of the stress ***,recent evidence suggests a growing concern in determining the correlation between the stress hormone level and its associated gene ***,this review highlights the regulation of stress responses in different axes,genetic and epigenetic factors related to stress,and the integration of recent technologies and novel hypotheses to unravel the stress response mechanism in fish reproduction.

关键词： Cortisol Interrenal axis Steroidogenesis Gonadotropins Chromaffin cells Catecholamines

先兆子痫患者的可溶性endoglin和其他循环血中抗血管形成因子

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世界核心医学期刊文摘（心脏病学分册） 2007年第2期3卷 12-13页

作者： Levine R.J. Lam C. 孙凯 nih/ nichd Bldg. 6100 Bethesda MD 20892 United States

背景:循环血中可溶性fms样酪氨酸激酶-1(sFlt1)(一种抗血管形成蛋白)和胎盘生长因子(PlGF)(一种前血管形成蛋白)的变化似乎参与了先兆子痫的发病机制。由于可溶性endoglin(另一种抗血管形成蛋白)与sFlt1联合作用可导致妊娠大鼠出现重度... 详细信息

背景:循环血中可溶性fms样酪氨酸激酶-1(sFlt1)(一种抗血管形成蛋白)和胎盘生长因子(PlGF)(一种前血管形成蛋白)的变化似乎参与了先兆子痫的发病机制。由于可溶性endoglin(另一种抗血管形成蛋白)与sFlt1联合作用可导致妊娠大鼠出现重度先兆子痫样综合征,故本研究中探讨了其与女性先兆子痫是否相关。

关键词：血管形成因子 endoglin 先兆子痫形成蛋白胎盘生长因子循环血大鼠未足月妊娠发病机制

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循环中的血管生成因子与胎盘早剥

世界核心医学期刊文摘（妇产科学分册） 2006年第11期2卷 61-62页

作者： Signore C. Mills J.L. R.J. Levine 柳蕴 nih/ nichd Building 6100 Bethesda MD 20892 United States Dr.

OBJECTIVE: Abnormalities in circulating angiogenic factors have been reported in diseases of abnormal placentation, such as preeclampsia and intrauterine growth restriction. Our objective was to determine whether circulating angiogenic factors are altered in another placental vascular disease, abruptio placentae. METHODS: In a nested case-control study of nulliparous pregnancies, we examined levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1) in serum collected prospectively from 31 women who later developed placental abruption and from 31 normal control subjects. All serum specimens were collected before the onset of hypertension or abruption and before labor or delivery. Serum angiogenic factors were compared within 3 gestational age windows: early (20 weeks or less), middle (21- 32 weeks), and late (33 weeks or more) pregnancy. RESULTS: During early pregnancy women who developed placental abruption had lower PlGF and higher sFlt- 1 concentrations and higher sFlt- 1/PlGF ratios than women with normal pregnancies. In mid- pregnancy these differences became greater, reaching statistical significance for PlGF concentration (431 versus 654 pg/mL, P < .01) and the sFlt- 1/PlGF ratio (25.3 versus 2.5, P < .01) . When the women with placental abruption were subdivided into those who did (n=10) and those who did not (n=21) develop preeclampsia or gestational hypertension, significant alterations in angiogenic factors were noted only in women who later developed hypertension in pregnancy. Among these women, PlGF concentrations were decreased in mid-pregnancy (160 versus 723 pg/mL, P < .001), and the mid-pregnancy sFlt- 1/PlGF ratio was increased (70.1 versus 2.3, P=.001). CONCLUSION: Serum levels of the proangiogenic factor PlGF were decreased, and those of the antiangiogenic ratio sFlt- 1/PlGF were increased in nulliparous women who subsequently devel-oped hypertension and placental abruption.

关键词：胎盘早剥血管生成因子胎盘生长因子胎盘形成妊娠中期妊娠高血压胎儿宫内生长先兆子痫血管生

Removal of Dominant Adrenal Lateralized by Glucagon-Stimulated Adrenal Venous Sampling Alleviates Hypertension in Bilateral Pheochromocytoma

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Journal of Life Sciences 2013年第6期7卷 586-591页

作者： Chandy Lou P. Malong Mary Jane Tanchee-Ngo Pilar Torres-Salvador Karel Pacak Leilani B.Mercado-Asis Section of Endocrinology and Metabolism Department of Medicine University of Santo Tomas Hospital Manila 1015Philippines Section of Medical Neuroendocrinology Reproductive and Adult Endocrinology Program NICHD (National Institute of ChildHealth and Human Development) NIH (National Institutes of Health) Bethesda 20892-1109 Maryland USA

In bilateral pbeochromocytoma, localization of the dominant adrenal is challenging but highly important since the removal of dominant side can markedly improve cardiovascular outcomes. To demonstrate the usefulness of glucagon-stimulated BAVS （bilateral adrenal venous sampling） in determining the dominant adrenal to be removed, the authors reviewed records of patients who underwent BAVS with glucagon stimulation from 1997-2010. Nineteen out of 44 patients were diagnosed with bilateral pheochromocytoma. Mean age at diagnosis was 33 ± 14 years. Duration of hypertension was 5 ± 6 years with highest systolic BP （blood pressure） of 186 ±30 mmHg and diastolic BP of 113 ±18 mmHg. Headache （68%） is the most common symptom followed by paroxysmal hypertension （58%）. Majority were taking 〉 3 anti-hypertensive drugs. On glucagon-stimulated BAVS, 63% had right adrenal dominance. Three patients, who were hypertensive for 1, 6 and 12 years, underwent removal of the dominant adrenal. On follow-up （mean period = 36 months）, there was marked improvement in BP control [pre-op vs. post-op：（systolic） 160-240 mmHg vs. 120-150 mmHg; （diastolic） 90-110 mmHg vs. 70-90 mmHg] and reduction in number of anti-hypertensive medications （from 3-5 to 2 classes of drugs）. BAVS with glucagon stimulation is a valuable tool in the identification of the dominant adrenal to be removed in patients with bilateral pheochromocytoma to alleviate chronic hypertension.

关键词： Adrenal sampling endocrine hypertension bilateral pheochromocytoma neuroendocrine tumor adrenalectomy.

Relevance of placental type I interferon beta regulation for pregnancy success

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Cellular & Molecular Immunology 2018年第12期15卷 1010-1026页

作者： Ja-Young Kwon Paulomi Aldo Yuan You Jiahui Ding Karen Racicot Xiaoyan Dong John Murphy Guy Glukshtad Michelle Silasi Jian Peng Li Wen Vikki MAbrahams Roberto Romero Gil Mor Division of Reproductive Sciences Department of ObstetricsGynecology and Reproductive SciencesYale School of MedicineNew HavenCTUSA Department of Obstetrics and Gynecology Institute of Women’s Life Medical ScienceYonsei University College of MedicineSeoulKorea Department of Obstetrics Gynecology&Reproductive BiologyCollege of Human MedicineMichigan State University400 Monroe Avenue NEGrand RapidsMI 49503USA Department of Pulmonary Shanghai Children’s HospitalShanghai Jiaotong University School of MedicineShanghaiChina Division of Endocrinology Department of Internal MedicineYale School of MedicineNew HavenCTUSA Perinatal Research Branch NICHD/NIHDetroitMIUSA

Pregnancy is a unique immunologic and microbial condition that requires an adequate level of awareness to provide a fast and protective response against pathogens as well as to maintain a state of tolerance to paternal *** of inflammatory pathways in the placenta triggered by pathogens is one of the main factors responsible for pregnancy *** I IFNs are key molecules modulating immune responses at the level of the placenta and are crucial for protection of the pregnancy via their antiviral and immune modulatory *** this study,we elucidate the mechanisms controlling the basal expression of IFNβand its negative *** in vitro and in vivo animal models,we found that TLR signaling maintains basal IFNβlevels through the TLR4-MyD88-independent TBK/IRF3 signaling *** describe the role of the TAM receptor Axl in the regulation of IFNβfunction in human and mouse trophoblast *** absence of TAM receptors in vivo is associated with fetal demise due to dysregulation of IFNβexpression and its pro-apoptotic downstream ***,our data describe a feedback signaling pathway controlling the expression and function of IFNβin the trophoblast that is essential for an effective response during viral and microbial infections.

关键词： trophoblast immune regulation cytokine TAM receptors type I interferon Interferon beta ISGs

自发性卵巢早衰女性生育脆性X染色体综合征儿

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世界核心医学期刊文摘（妇产科学分册） 2006年第3期2卷 38-38页

作者： Corrigan E.C. Raygada M.J. Vanderhoof V.H. Nelson L.M. 李跃萍 DEB/nichd/nih CRCMSC-1103 10 Center Drive Bethesda MD 20892-1103 United States Dr.

Objective: To inform clinicians about a reproductive risk associated with spontaneous premature ovarian failure and the fragile X mental retardation 1 gene (FMR1). Design: Case report. Setting: National Institutes of Health Clinical Center. Patient(s): A 35-year-old woman with confirmed spontaneous premature ovarian failure. Intervention(s): FMR1 genetic testing. Main Outcome Measure(s): Number of CGG trinucleotide repeats in the 5′untranslated region of FMR1. Result(s): Despite having ovarian failure the woman subsequently conceived and delivered a son with fragile X syndrome (>200 CGG repeats). She was then found to carry an FMR1 premutation (85 CGG repeats). Conclusion(s): This is a real-life manifestation of a theoretical risk; a woman conceived subsequent to the diagnosis of spontaneous premature ovarian failure and has a child who manifests mental retardation due to fragile X syndrome. Women with spontaneous premature ovarian failure are at increased risk of having an FMR1 premutation and should be informed of the availability of fragile X testing. Should an FMR1 premutation be uncovered, this will allow patients to make informed reproductive decisions and help clinicians to properly diagnose family members who may have menstrual irregularity, developmental delay, or neurologic symptoms.

关键词：卵巢早衰女性生育前突变智力发育迟缓串联重复临床中心三核苷酸月经不调临床医生非翻译区

An imbalance between innate and adaptive immune cells at the maternal-fetal interface occurs prior to endotoxin-induced preterm birth

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Cellular & Molecular Immunology 2016年第4期13卷 462-473页

作者： Marcia Arenas-Hernandez Roberto Romero Derek St Louis Sonia S Hassan Emily B Kaye Nardhy Gomez-Lopez Department of Obstetrics & Gynecology Wayne State University School of Medicine Detroit Michigan USA perinatology Research Branch Program for Perinatal Research and Obstetrics Division of Intramural Research Eunice Kennedy ShriverNational Institute of Child l~ealth and Human DevelopmentNIC.HD/NIHDHHS Bethesda Maryland and Detroit Michigan USA Departme.nt of Obstetrics and Gynecology University of M chigan Ann ArborMichigan USA Department of Epidemiology and Biostatistics Michigan State University East Lansing Michigan USA Department of Molecular Obstetrics and Genetics Wayne State University Detroit Michigan USA Department of ImmunoLogy & MicrobioLogy Wayne State University School of Medicine Detroit Michigan USA

Preterm birth （PTB） is the leading cause of neonatal morbidity and mortality worldwide. A transition from an anti-inflammatory state to a pro-inflammatory state in the mother and at the maternal-fetal interface has been implicated in the pathophysiology of microbial-induced preterm labor. However, it is unclear which immune cells mediate this transition. We hypothesized that an imbalance between innate and adaptive immune cells at the maternal-fetal interface will occur prior to microbial-induced preterm labor. Using an established murine model of endotoxin-induced PTB, our results demonstrate that prior to delivery there is a reduction of CD4 ＋ regulatory T cells （Tregs） in the uterine tissues. This reduction is neither linked to a diminished number of Tregs in the spleen, nor to an impaired production of ILIO, CCL17, or CCL22 by the uterine tissues. Endotoxin administration to pregnant mice does not alter effector CD4＋ T cells at the maternal-fetal interface. However, it causes an imbalance between Tregs （CD4＋ and CD8＋）, effector CD8＋ T cells, and Th17 cells in the spleen. In addition, endotoxin administration to pregnant mice leads to an excessive production of CCL2, CCL3, CCL17, and CCL22 by the uterine tissues as well as abundant neutrophils. This imbalance in the uterine microenvironment is accompanied by scarce APC-like cells such as macrophages and MHC II ＋ neutrophils. Collectively, these results demonstrate that endotoxin administration to pregnant mice causes an imbalance between innate and adaptive immune cells at the maternal-fetal interface.

关键词： antigen-presenting cells effector T cells inflammation labor lipopolysaccharide macrophages microbial product neutrophils pregnancy preterm labor regulatory T cells