Progesterone Regulation of Endometrial Gene Expression in the Early Pregnant Ovine Uterus PDF Download
Are you looking for read ebook online? Search for your book and save it on your Kindle device, PC, phones or tablets. Download Progesterone Regulation of Endometrial Gene Expression in the Early Pregnant Ovine Uterus PDF full book. Access full book title Progesterone Regulation of Endometrial Gene Expression in the Early Pregnant Ovine Uterus by Megan A. Minten. Download full books in PDF and EPUB format.
Author: Megan A. Minten
Publisher:
ISBN:
Category :
Languages : en
Pages :
Get Book Here
Book Description
Establishment of pregnancy in ruminants requires blastocyst development to form an elongated filamentous conceptus that produces interferon tau (IFNT), the pregnancy recognition signal, and initiate implantation. Blastocyst growth and development is dependent upon secretions from the uterine endometrium. An early increase in post-ovulatory circulating levels of progesterone (P4) stimulates blastocyst growth and conceptus elongation in ruminants. Microarray analysis was used to identify candidate P4-regulated genes and regulatory networks in the endometrium that govern peri-implantation blastocyst/conceptus growth and development. The first study was conducted to validate effects of P4 and/or pregnancy on expression of candidate genes identified by microarray analysis. The genes included: ANGPTL3, CHGA, CLEC4E, CXCL14, EFNA1, EFNB1, FABP3, IFNG, IL6, LGALS3, PTH, RBP4, SLIT2, SLIT3, and VWF. Early P4 treatment up-regulated CXCL14 gene expression in Day 9 ovine endometrium compared to control endometrium, and FABP3, IFNG, IL6 and LGALS3 in Day 12 early P4-treated ovine endometrium. Expression of ANGPTL3, CHGA, CXCL14, EFNA1, EFNB1, LGALS3 and RBP4 was affected by day of pregnancy. Treatment of ewes with P4+RU486 (P4 receptor antagonist) reduced expression of ANGPTL3, CHGA, EFNA1, EFNB1, FABP3, IFNG, IL6, LGALS3, RBP4, and SLIT2, SLIT3 and VWF in comparison to Day 12 P4-treated endometrium. The second study evaluated expression of genes identified by microarray analysis in endometrium from pregnant and cyclic ewes. Genes evaluated included those from the first study. ANGPTL3, CHGA, CXCL14, EFNA1, EFNB1, IFNG, LGALS3, PTH, RBP4, SLIT2, SLIT3 and VWF were affected by day, status and/or their interaction between Days 10 and 16. Of note, FABP3 increased 21-fold between Days 14 to 18 of pregnancy, and IL6 increased 37-fold between Days 14 to 20 of pregnancy. In situ hybridization analysis detected FABP3 mRNA in both luminal and superficial glandular epithelia of pregnant ewes and trophectoderm, whereas IL6 mRNA was detected in immune cells within uterine luminal epithelium and glandular epithelium and trophectoderm. Collectively, these results identify candidate genes encoding for biologically active molecules that regulate growth and development of the ovine conceptus during the peri-implantation period of pregnancy.
Author: Megan A. Minten
Publisher:
ISBN:
Category :
Languages : en
Pages :
Get Book Here
Book Description
Establishment of pregnancy in ruminants requires blastocyst development to form an elongated filamentous conceptus that produces interferon tau (IFNT), the pregnancy recognition signal, and initiate implantation. Blastocyst growth and development is dependent upon secretions from the uterine endometrium. An early increase in post-ovulatory circulating levels of progesterone (P4) stimulates blastocyst growth and conceptus elongation in ruminants. Microarray analysis was used to identify candidate P4-regulated genes and regulatory networks in the endometrium that govern peri-implantation blastocyst/conceptus growth and development. The first study was conducted to validate effects of P4 and/or pregnancy on expression of candidate genes identified by microarray analysis. The genes included: ANGPTL3, CHGA, CLEC4E, CXCL14, EFNA1, EFNB1, FABP3, IFNG, IL6, LGALS3, PTH, RBP4, SLIT2, SLIT3, and VWF. Early P4 treatment up-regulated CXCL14 gene expression in Day 9 ovine endometrium compared to control endometrium, and FABP3, IFNG, IL6 and LGALS3 in Day 12 early P4-treated ovine endometrium. Expression of ANGPTL3, CHGA, CXCL14, EFNA1, EFNB1, LGALS3 and RBP4 was affected by day of pregnancy. Treatment of ewes with P4+RU486 (P4 receptor antagonist) reduced expression of ANGPTL3, CHGA, EFNA1, EFNB1, FABP3, IFNG, IL6, LGALS3, RBP4, and SLIT2, SLIT3 and VWF in comparison to Day 12 P4-treated endometrium. The second study evaluated expression of genes identified by microarray analysis in endometrium from pregnant and cyclic ewes. Genes evaluated included those from the first study. ANGPTL3, CHGA, CXCL14, EFNA1, EFNB1, IFNG, LGALS3, PTH, RBP4, SLIT2, SLIT3 and VWF were affected by day, status and/or their interaction between Days 10 and 16. Of note, FABP3 increased 21-fold between Days 14 to 18 of pregnancy, and IL6 increased 37-fold between Days 14 to 20 of pregnancy. In situ hybridization analysis detected FABP3 mRNA in both luminal and superficial glandular epithelia of pregnant ewes and trophectoderm, whereas IL6 mRNA was detected in immune cells within uterine luminal epithelium and glandular epithelium and trophectoderm. Collectively, these results identify candidate genes encoding for biologically active molecules that regulate growth and development of the ovine conceptus during the peri-implantation period of pregnancy.
Author: Michael Carey Satterfield
Publisher:
ISBN:
Category :
Languages : en
Pages :
Get Book Here
Book Description
Progesterone is unequivocally required for the establishment and maintenance of pregnancy in all mammals studied. Its known functions are complex and encompass global changes in gene expression. Therefore, studies were conducted to characterize the effects of progesterone on expression of genes for endometrial factors having roles in conceptus growth, implantation and establishment of pregnancy. The first study characterized the effect of an artificially induced early increase in circulating progesterone on conceptus growth and development and regulation of expression of galectin-15 (LGALS15), a recently identified protein secreted by the ovine uterine luminal epithelium (LE). Exogenous progesterone beginning on Day 1.5 post-mating accelerated conceptus development on Days 9 and 12. On Day 12 the conceptus was functionally and morphologically advanced to produce greater quantities of interferon tau (IFNT) than blastocysts from control ewes. Further, the endometrium responded to early progesterone and IFNT with early expression of cathepsin L (CTSL), radical S-adenosyl methionine domain containing 2 (RSAD2), and LGALS15 within the endometrium. The second study identifed structural changes within the luminal epithelium which could alter the flux of factors into and out of the uterine lumen to maintain appropriate fetal/maternal communication. In this study, progesterone reduced quantities of proteins associated with both tight and adherens junctions during the elongation period. IFNT subsequently increased these proteins after conceptus elongation. The third and fourth studies identified progesterone-regulated genes which have been implicated as having importance to implantation in sheep, mouse, and human. WNT signaling was transiently downregulated by progesterone, while members of several growth factor families are upregulated including insulin-like growth factor binding proteins (IGFBPs) 1 and 3, hepatocyte growth factor (HGF) and fibroblast growth factor 7 (FGF7), which may enhance conceptus growth. Collectively, these studies assess the role of progesterone in altering gene uterine expression to establish a favorable environment for conceptus development. The long-term goals of these studies are to establish biomarkers of receptivity to conceptus development and implantation, enhance our understanding of gene and pathway regulation in early pregnancy loss, and identify genes which may be targeted in therapeutic strategies to improve reproductive success in humans and animals.
Author: Hyo Won Ahn
Publisher:
ISBN:
Category :
Languages : en
Pages :
Get Book Here
Book Description
During early pregnancy in ruminants, progesterone (P4) from the corpus luteum (CL) and interferon tau (IFNT) from the conceptus act on the endometrium to regulate genes including interferon stimulated genes (ISGs) that are hypothesized to be important for uterine receptivity and conceptus growth. Previous custom ovine cDNA array analyses identified candidate genes that were regulated by pregnancy, P4 and/or IFNT in the ovine uterus. The first study validated pregnancy, P4 and/or IFNT regulated genes identified by previous custom ovine cDNA microarray analyses. ACTA2, COL3A1, POSTN, SPARC, S100A2, STAT5A and TAGLN were examined. POSTN was upregulated by P4 and S100A2 was downregulated by IFNT. Moreover, functional studies showed that POSTN stimulated attachment of ovine trophectoderm cells. However, neither COL3A1, SPARC, ACTA2 nor TAGLN was regulated by pregnancy, P4 or IFNT in the ovine endometrium. Collectively, these results confirmed that POSTN and S100A2 are P4 and IFNT regulated, respectively, and likely involved in uterine receptivity to conceptus implantation during early pregnancy. The second study determined expression of ISGs in the CL of pregnant ewes. MX1, MX2, ISG15, OAS1, and RSAD2 mRNAs were increased on Day 14 of pregnancy and maintained to Day 18, indicating that IFNT induced expression of ISGs in the CL. These results confirmed that locally produced IFNT has paracrine effects and also endocrine effects on reproductive organs other than the uterine endometrium and maternal immune system.
Author: Joanne Kwak-Kim
Publisher: Springer
ISBN: 9783030285869
Category : Health & Fitness
Languages : en
Pages : 0
Get Book Here
Book Description
The endometrium goes through cyclical changes under the influence of hormones, and immune effectors in the endometrium change their populations cyclically as well. Dynamic changes in immune effectors determine endometrial cytokine and chemokine milieus and, consequently, the endometrial immune response. Endometrial immune responses have been shown to be important for trophoblast invasion and early pregnancy. Indeed, dysregulated endometrial inflammatory immune responses are associated with reproductive failures, such as recurrent pregnancy losses, repeated implantation failure, and gynecological diseases with oncogenic potential. Hence, the investigation of endometrial gene expression may predict infertility, gynecological and oncological conditions. This book presents the state of the art in endometrial gene expression as well as recent developmental findings relating to reproduction and reproductive disorders. It begins with a review of the genetic regulation of urogenital tract formation and molecular mechanism underlying the physiology of menstrual cycle before moving on to the current and emerging technological advances in molecular biology. Endometrial gene expressions of immune inflammatory conditions, viral infection, metabolic and nutritional conditions, and reproductive disorders are then presented in following chapters. Examples of the use and interpretation of gene expression in clinical scenarios including recurrent pregnancy losses, infertility and multiple implantation failures are presented with currently available endometrial gene analysis. Utilizing the latest evidence and clinical guidelines, Endometrial Gene Expression will be a cutting-edge resource for gynecologist, reproductive immunologist, reproductive endocrinologists, obstetrician, maternal fetal medicine specialist and other health care providers in the field of reproductive medicine.
Author: Fuller W. Bazer
Publisher: Springer Science & Business Media
ISBN: 1461218047
Category : Medical
Languages : en
Pages : 579
Get Book Here
Book Description
A comprehensive, cutting-edge review of the complex interactions between maternal and fetal-placental tissues that control the establishment and maintenance of pregnancy, the proper development of the fetus, the birth process, and the behavioral aspects of bonding between mother and newborn. Expert researchers review the endocrine and physiological events that culminate in the delivery of offspring, and provide a solid base of comparative information on the menstrual cycle of primates, including humans. They also discuss the sources and functions of both steroid and protein hormones from the placenta and the details of their effects on uterine function, placental development, fetal growth and well-being, and maternal responses to pregnancy. This book will become the standard reference source not only for reproductive scientists, but also for those clinicians who want better to understand the complex factors that affect pregnancy-and their pregnant patients.
Author: Rodney D. Geisert
Publisher: Springer
ISBN: 3319158562
Category : Medical
Languages : en
Pages : 271
Get Book Here
Book Description
Over the past few decades technological advances in transcriptomics, proteomics, metabolomics, and glycomics along with the ability to selectively knockout genes of interest has greatly advanced our understanding of maternal-conceptus interactions that are essential for the establishment and maintenance of a successful pregnancy. This knowledge provides a foundation from which to build research endeavors to help resolve infertility, embryonic loss and recurrent abortion in humans, captive wild animals and important farm species. The present volume on “Regulation of Implantation and Establishment of Pregnancy in Mammals” brings together current reviews from leading experts to address the diversity of mechanisms by which species establish and maintain pregnancy. Implantation in rodents, dogs, pigs, cattle, sheep, horses, primates, humans and embryonic diapause in wild species are discussed. Reviews will provide current knowledge on the role of endometrial steroid receptors, adhesion factors, cytokines, interferons, steroids, prostaglandins, growth factors and immune cells involved with regulation of conceptus development.
Author: Catherine Allison Gray
Publisher:
ISBN:
Category :
Languages : en
Pages :
Get Book Here
Book Description
Recurrent early pregnancy loss in the ovine uterine gland knockout (UGKO) ewe model manifests on Day 14 of pregnancy, indicating that endometrial secretions are critical for peri-implantation conceptus development. Therefore, the following studies were conducted with fertile ewes and infertile UGKO ewes to identify candidate endometrial factors essential for normal conceptus survival, utilizing both genomics and proteomics approaches. The first study used transcriptional profiling of endometrium from Day 14 cyclic, pregnant, and bred UGKO ewes, as well as ewes treated with interferon tau (IFN[subscript]tau) and progesterone, to identify genes important for conceptus development. A number of novel and previously known IFN[subscript]tau-stimulated genes, as well as progesterone-stimulated genes were identified that are higher in fertile ewes, such as galectin-15. Interactive effects of progesterone and IFN[subscript]tau regulate endometrial gene expression in a temporal and cell-type specific manner. The second study characterized the endometrial expression and hormonal regulation of galectin-15, a member of the galectin family of secreted [Beta]-galactoside lectins. Galectin-15 was secreted into the uterine lumen by the lumenal (LE) and superficial glandular epithelium (sGE), where it may promote adhesion during implantation, as well as was phagocytosed by the trophectoderm and formed intracellular crystals. The third study determined the endometrial expression of galectin-15 throughout gestation. Galectin-15 was secreted into the uterine lumen, where it was phagocytosed by the trophectoderm/chorion, transferred through placental vasculature to the fetus, and cleared through the fetal kidney to be stored in allantoic fluid. The fourth study utilized proteomic analysis of uterine flushes and endometrial explant cultures from Day 14 cyclic, pregnant and UGKO ewes to identify differences in uterine secretions. Analyses identified several genes that were expressed by the LE and sGE and may be involved in prostaglandin production and/or pH regulation. Collectively, results of these studies suggest that transcriptional profiling and analysis of uterine secretions are effective tools to determine genes important for early pregnancy. Further, identified genes are expected to reveal novel endometrial factors and metabolic pathways for support of conceptus survival and implantation, as well as provide improvements for embryo culture methods and diagnose endometrial dysfunctions leading to infertility.
Author: Julie Whelan
Publisher: John Wiley & Sons
ISBN: 0470718145
Category : Medical
Languages : en
Pages : 192
Get Book Here
Book Description
The Novartis Foundation Series is a popular collection of the proceedings from Novartis Foundation Symposia, in which groups of leading scientists from a range of topics across biology, chemistry and medicine assembled to present papers and discuss results. The Novartis Foundation, originally known as the Ciba Foundation, is well known to scientists and clinicians around the world.
Author: Gwon Hwa Song
Publisher:
ISBN:
Category :
Languages : en
Pages :
Get Book Here
Book Description
The peri-implantation period in mammals is critical with respect to survival of the conceptus and establishment of pregnancy. During this period of pregnancy, reciprocal communication between ovary, conceptus, and endometrium is required for successful implantation and placentation. Therefore, studies were conducted to indentify and characterize novel endometrial genes important for implantation and conceptus development in the ovine uterus. The first and second studies defined the uterine expression of seven members of the cathepsin (CTS) family of lysosomal proteases, and a secreted inhibitor of CTSL called cystatin C (CST3) during the peri-implantation period. In addition, regulation of CTS and CST3 by progesterone (P4) and interferon tau (IFNT) was evaluated. CTSL was the most abundant CTS in the ovine ovine uterus and was also coordinately expressed with CST3 in the endometrial epithelia and conceptus trophectoderm. CTSL and CST3 were found to be novel P4-induced and IFNT-stimulated genes in the luminal epithelial cells of the ovine endometrium. The third study identified radical S-adenosyl methionine domain containing 2 (RSAD2) and interferon-induced with helicase C domain 1 (IFIH1) in the ovine uterus. Results of this study indicated that IFNT induces RSAD2 and IFIH1 in a P4-independent manner in the stroma, immune cells, and glands of the ovine endometrium. These two genes are proposed to have biological roles in the establishment of uterine receptivity to the conceptus during implantation. The fourth study characterized endometrial expression of stanniocalcins (STC) during pregnancy. STC1 appeared in the endometrial glands on Day 18 of pregnancy, increased from Days 18 to 80, and remained abundant through Day 120 of gestation. In addition, this study demonstrated that STC1 is induced by P4 and increased by placental hormones, such as placental lactogen (CSH1) and growth hormone (GH), in the ovine endometrial glands. Collectively, these studies identified genes that are expected to be critical to unraveling the mechanism(s) of reciprocal fetal-maternal interactions required for successful implantation and pregnancy. A more complete understanding of these genes will be important for developing therapeutic strategies to prevent, treat and/or diagnose infertility in domestic animals and humans, because they are biomarkers of P4 and/or IFN effects.
Author: Piotr Dorniak
Publisher:
ISBN: 9781303240737
Category :
Languages : en
Pages :
Get Book Here
Book Description
Pregnancy failure during the early stage of gestation is a major cause of infertility in domestic ruminants. Most early pregnancy losses are characterized by endometrial dysfunction, asynchrony between the conceptus (embryo and outer trophectoderm) and uterus, or failure in conceptus development. During early pregnancy in sheep, endometrial functions are primarily regulated by ovarian progesterone (P4) and interferon tau (IFNT) from the conceptus trophectoderm. The endometrium and conceptus synthesize prostaglandins (PGs) via prostaglandin synthase two (PTGS2) and cortisol via hydroxysteroid (11-beta) dehydrogenase 1 (HSD11B1). The central hypothesis is that endometrial functions supporting conceptus elongation in ruminants are regulated by hormones produced by the ovary (P4), conceptus (IFNT, PGs, and cortisol) and perhaps endometrium itself (PGs, cortisol). The hypothesis was addressed by determining the physiological roles of: (1) PTGS2 and PGs in conceptus development; (2) PTGS2-derived PGs in P4, IFNT and cortisol regulation of endometrial function; (3) HSD11B1 and cortisol in conceptus elongation; and (4) HSD11B1-derived cortisol in P4, IFNT and PGs regulation of endometrial function. Functional studies utilizing osmotic pumps were conducted to infuse selective agents inhibiting PG biosynthesis and/or cortisol production in utero or to deliver pregnancy levels of hormones (IFNT, PGs, and cortisol) directly into the uterine lumen of sheep. Results of the studies established that: (1) PGs and cortisol are important regulators of conceptus elongation; (2) PGs mediate, in part, effects of P4 and IFNT on endometrial gene expression and function; (3) PGs stimulate endometrial HSD11B1 expression and cortisol production; (4) cortisol regulates conceptus elongation; (5) cortisol modulates effects of ovarian P4 on endometrial gene expression; (6) cortisol stimulates endometrial PTGS2 activity and PG production. Collectively, results of these studies support the idea that PGs and cortisol are important regulators of endometrial function and conceptus elongation during early pregnancy in ruminants. Knowledge gained from these studies provides new insight into the physiological pathways governing interactions between the conceptus and its uterine environment. Information from these studies provides a foundation for future translation research that is necessary to increase fertility of domestic ruminants.
