Sumario:
The International Journal of Developmental Biology
Linking Development, Stem Cells and Cancer Research
Euskal Herriko Unibertsitateko Argitalpen Zerbitzua / Servicio Editorial de la Universidad del País Vasco / University of the Basque Country Press
Volume 58 - Numbers 2-3-4 (2014) / Pages 71-298 Editor-in-Chief: Juan Aréchaga
MORE INFORMATION [Abstract - FullText / FullText Open Access]
ISSN: 0214-6282 / ISSN-e: 1696-3547 www.intjdevbiol.com
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Special Issue: Embryo Implantation
Guest Editor: Michael J. Soares
CONTENTS + ABSTRACTS
Preface
Embryo implantation - coordination of maternal and embryonic adaptations
Michael J. Soares
EHU/UPV/UBC - The International Journal of Developmental Biology (2014) 58: 71-74
Historical approach and interviews
Decidua and implantation of the embryo from a historical perspective
Ivan Damjanov
EHU/UPV/UBC - The International Journal of Developmental Biology (2014) 58: 75-78
A lifetime of deciphering complexities of embryo implantation
Susanne Tranguch and Sudhansu K. Dey
EHU/UPV/UBC - The International Journal of Developmental Biology (2014) 58: 79-86
Exploring the world of human development and reproduction
Kristy Red-Horse, Penelope M. Drake and Susan Fisher
EHU/UPV/UBC - The International Journal of Developmental Biology (2014) 58: 87-93
Uterine biology, epithelial-stromal interactions, and decidualization
Progesterone receptor signaling in the initiation of pregnancy and preservation of a healthy uterus
Margeaux Wetendorf and Francesco J. DeMayo
EHU/UPV/UBC - The International Journal of Developmental Biology (2014) 58: 95-106
Uterine glands: biological roles in conceptus implantation, uterine receptivity and decidualization
Justyna Filant and Thomas E. Spencer
EHU/UPV/UBC - The International Journal of Developmental Biology (2014) 58: 107-116
Evolution of mammalian pregnancy and the origin of the decidual stromal cell
Günter P. Wagner, Koryu Kin, Louis Muglia and Mihaela Pavlièev
EHU/UPV/UBC - The International Journal of Developmental Biology (2014) 58: 117-126
Transcriptomics of the human endometrium
Patricia Díaz-Gimeno, Maria Ruíz-Alonso, David Blesa and Carlos Simón
EHU/UPV/UBC - The International Journal of Developmental Biology (2014) 58: 127-137
Role of uterine stromal-epithelial crosstalk in embryo implantation
Alison M. Hantak, Indrani C. Bagchi and Milan K. Bagchi
EHU/UPV/UBC - The International Journal of Developmental Biology (2014) 58: 139-146
Molecular determinants of uterine receptivity
Zhaowei Tu, Hao Ran, Shuang Zhang, Guoliang Xia, Bingyan Wang and Haibin Wang
EHU/UPV/UBC - The International Journal of Developmental Biology (2014) 58: 147-154
Embryo-uterine interactions
The evolution of embryo implantation
Michael R. McGowen, Offer Erez, Roberto Romero and Derek E. Wildman
EHU/UPV/UBC - The International Journal of Developmental Biology (2014) 58: 155-161
Embryonic diapause: development on hold
Jane C. Fenelon, Arnab Banerjee and Bruce D. Murphy
EHU/UPV/UBC - The International Journal of Developmental Biology (2014) 58: 163-174
Embryo-endometrial interactions during early development after embryonic diapause in the marsupial tammar wallaby
Marilyn B. Renfree and Geoff Shaw
EHU/UPV/UBC - The International Journal of Developmental Biology (2014) 58: 175-181
Evolving tales of autophagy in early reproductive events
Hyunjung J. Lim and Haengseok Song
EHU/UPV/UBC - The International Journal of Developmental Biology (2014) 58: 183-187
Maternal immune/inflammatory cells and the establishment of pregnancy
T cell behavior at the maternal-fetal interface
Patrice Nancy and Adrian Erlebacher
EHU/UPV/UBC - The International Journal of Developmental Biology (2014) 58: 189-198
Uterine natural killer cells as modulators of the maternal-fetal vasculature
Brooke C. Matson and Kathleen M. Caron
EHU/UPV/UBC - The International Journal of Developmental Biology (2014) 58: 199-204
Immunological determinants of implantation success
Sarah A. Robertson and Lachlan M. Moldenhauer
EHU/UPV/UBC - The International Journal of Developmental Biology (2014) 58: 205-217
Natural killer cells and regulatory T cells in early pregnancy loss
Surendra Sharma
EHU/UPV/UBC - The International Journal of Developmental Biology (2014) 58: 219-229
Trophoblast development and actions on the maternal interface
DNA methylation and its role in the trophoblast cell lineage
Satoshi Tanaka, Momo O. Nakanishi and Kunio Shiota
EHU/UPV/UBC - The International Journal of Developmental Biology (2014) 58: 231-238
BMP4 regulation of human trophoblast development
Yingchun Li and Mana M. Parast
EHU/UPV/UBC - The International Journal of Developmental Biology (2014) 58: 239-246
Adaptive mechanisms controlling uterine spiral artery remodeling during the establishment of pregnancy
Michael J. Soares, Damayanti Chakraborty, Kaiyu Kubota, Stephen J. Renaud and M.A. Karim Rumi
EHU/UPV/UBC - The International Journal of Developmental Biology (2014) 58: 247-259
Cell signaling in trophoblast-uterine communication
Rani Fritz, Chandni Jain and D. Randall Armant
EHU/UPV/UBC - The International Journal of Developmental Biology (2014) 58: 261-271
Pregnancy-specific glycoproteins: complex gene families regulating maternal-fetal interactions
Tom Moore and Gabriela S. Dveksler
EHU/UPV/UBC - The International Journal of Developmental Biology (2014) 58: 273-280
The role of trophoblastic microRNAs in placental viral infection
Jean-Francois Mouillet, Yingshi Ouyang, Avraham Bayer, Carolyn B. Coyne, and Yoel Sadovsky
EHU/UPV/UBC - The International Journal of Developmental Biology (2014) 58: 281-289
Epigenetics, development and disease
Epigenetics and imprinting in human disease
Jennifer M. Kalish, Connie Jiang and Marisa S. Bartolomei
EHU/UPV/UBC - The International Journal of Developmental Biology (2014) 58: 291-298
The International Journal of Developmental Biology
ISSN 1696-3547 (online) and 0214-6282 (print)
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Special Issue: Embryo Implantation
ABSTRACTS
Preface
EHU/UPV/UBC - The International Journal of Developmental Biology 58: 71-74 (2014)
doi: 10.1387/ijdb.140086ms / © UBC Press (www.a360grados.net)
Embryo implantation - coordination of maternal and embryonic adaptations
Michael J. Soares
Institute for Reproductive Health and Regenerative Medicine, University of Kansas Medical Center, Kansas City, USA
ABSTRACT: Viviparity is the process of a fertilized egg growing and developing within the mother (Amoroso, 1968). The process has inherent benefits, including a level of protection from predators and need-based delivery of nutrients. The oppor-tunity of the embryo to develop within the female reproductive tract is met with many challenges. These challenges are addressed with specializations within the embryo and uterus and an elaborate system of controls. Research has fo-cused on the female reproductive tract and its transformation into a safe haven facilitating embryonic and fetal devel-opment and on the extraembryonic specializations derived from the embryo. Collectively these events comprise em-bryo implantation. Coordination of parallel processes in maternal and embryonic compartments is a necessity. This Special Issue of the International Journal of Developmental Biology provides a forum for a talented group of experi-mentalists actively pursuing research addressing a range of scientific questions related to embryo implantation.
Keywords: Embryo implantation
Historical approach and interviews -----------------------------------------
EHU/UPV/UBC - The International Journal of Developmental Biology 58: 75-78 (2014)
doi: 10.1387/ijdb.140075id / © UBC Press (www.a360grados.net)
Decidua and implantation of the embryo from a historical perspective
Ivan Damjanov
Department of Pathology and Laboratory Medicine, The University of Kansas School of Medicine, Kansas City, Kansas, USA
ABSTRACT: Implantation of the embryo is critical for the initiation of intrauterine development of early embryos. It depends on the proper soil formed by the decidualized pregnant uterus. In the present article I have reviewed the evolution of the modern concepts of decidualization and embryonic implantation, emphasizing how closely interrelated these two processes are. Special emphasis and recognition is given to the Boston pathologist Arthur T. Hertig, who studied for 15 years with another Bostonian, John Rock, a gynecologist, human implantation and early embryogenesis, thus providing the basis for future studies of human reproductive biology, infertility and contraception.
Keywords: implantation, decidua, history
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EHU/UPV/UBC - The International Journal of Developmental Biology 58: 79-86 (2014)
doi: 10.1387/ijdb.130332st / © UBC Press (www.a360grados.net)
A lifetime of deciphering complexities of embryo implantation
Susanne Tranguch 1 and Sudhansu K. Dey 2
1. Office of Science and Research, New York University Langone Medical Center, New York, NY
2. Division of Reproductive Sciences, Perinatal Institute, Cincinnati Children's Research foundation, Cincinnati, Ohio, USA
ABSTRACT: This interview chronicles the story of Sudhansu K. Dey in his journey from Calcutta, India to Kansas City, Kansas, establishing a research enterprise in the field of female reproduction. His research of over four decades has focused specifically on implantation biology using various model systems and reveling the impact of implantation on female reproductive medicine. This interview also reveals qualities of SK’s character – his resolution, mentoring spirit, and humble nature – that contributed to his successes. SK is not shy to approach individuals for expertise or help, and in the same spirit, he is ready to offer his help to others irrespective of their positions or stature. He constantly attributes his success to the hard work of his laboratory members, the intellectual stimulation from his collaborators, and the support from his family. His ability to overcome challenges throughout his career is a reminder to students and junior investigators in the scientific community that each individual is endowed with talents and can accomplish their dreams if they pursue them. This interview tells the story of how he progressed from an inquisitive child to becoming a true servant to the cause of science and humankind.
Keywords: implantation, pregnancy, embryo, uterus, estrogen
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EHU/UPV/UBC - The International Journal of Developmental Biology 58: 87-93 (2014)
doi: 10.1387/ijdb.140063kr / © UBC Press (www.a360grados.net)
Exploring the world of human development and reproduction
Kristy Red-Horse 1, Penelope M. Drake 2 and Susan Fisher 3
1. Department of Biological Sciences, Stanford University, Stanford
2. Redwood Bioscience, Hollis St. Emeryville, CA, USA
3. Department of Obstetrics and Gynecology, the Center for Reproductive Sciences, and The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, California, USA.
ABSTRACT: Susan Fisher has spent her career studying human development, proteomics, and the intersection between the two. When she began studying human placentation, there had been extensive descriptive studies of this fascinating organ that intertwines with the mother’s vasculature during pregnancy. Susan can be credited with numerous major findings on the mechanisms that regulate placental cytotrophoblast invasion. These include the discovery that cytotrophoblasts undergo vascular mimicry to insert themselves into uterine arteries, the finding that oxygen tension greatly effects placentation, and identifying how these responses go awry in pregnancy complications such as preeclamsia. Other important work has focused on the effect of post-translational modifications such as glycosylation on bacterial adhesion and reproduction. Susan has also forayed into the world of proteomics to identify cancer biomarkers. Because her work is truly groundbreaking, many of these findings inspire research in other laboratories around the world resulting in numerous follow up papers. Likewise, her mentoring and support inspires young scientists to go on and make their own important discoveries. In this interview, Susan shares what drove her science, how she continued to do important research while balancing other aspects of life, and provides insights for the next generation.
Keywords: placenta, angiogenesis, implantation, pre-eclampsia, VEGF
Uterine biology, epithelial-stromal interactions, and decidualization -----------------
EHU/UPV/UBC - The International Journal of Developmental Biology 58: 95-106 (2014)
doi: 10.1387/ijdb.140069mw / © UBC Press (www.a360grados.net)
Progesterone receptor signaling in the initiation of pregnancy and preservation of a healthy uterus
Margeaux Wetendorf 1,2 and Francesco J. DeMayo 2,1
1. Integrative Molecular and Biomedical Sciences Graduate Program
2. Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA
ABSTRACT: Infertility and reproductive-associated disease are global problems in the world today affecting millions of women. A successful pregnancy requires a healthy uterus ready to receive and support an implanting embryo. As an endocrine organ, the uterus is dependent on the secretions of the ovarian hormones estrogen and progesterone which signal via their cognate receptors, the estrogen and progesterone receptors. The progesterone receptor not only functions using classical nuclear receptor signaling, but also participates in non-genomic signaling at the cellular membrane. The complexity of progesterone signaling is further enhanced by the existence of multiple isoforms and post-translational regulation via kinases and transcription coregulators. This dynamic means of regulation of the progesterone receptor is evidenced in its necessary role in a successful pregnancy. Within early pregnancy, the progesterone receptor elicits activation of its target genes in a spatiotemporal manner in order to allow for successful embryo attachment and uterine decidualization. Additionally, appropriate progesterone signaling is important for the prevention of uterine disease such as endometrial cancer, endometriosis, and leiomyoma. The utilization of progesterone receptor modulators in the treatment of these devastating uterine diseases is promising. This review presents a general overview of progesterone receptor structure, function, and regulation and highlights its important role in the establishment of pregnancy and as a therapeutic target in uterine disease.
Keywords: progesterone signaling, progesterone receptor, early pregnancy, mouse model
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EHU/UPV/UBC - The International Journal of Developmental Biology 58: 107-116 (2014)
doi: 10.1387/ijdb.130344ts / © UBC Press (www.a360grados.net)
Uterine glands: biological roles in conceptus implantation, uterine receptivity and decidualization
Justyna Filant and Thomas E. Spencer
Department of Animal Sciences and Center for Reproductive Biology, Washington State University, Pullman, WA, USA
ABSTRACT: All mammalian uteri contain glands in the endometrium that synthesize or transport and secrete substances essential for survival and development of the conceptus (embryo/fetus and associated extraembryonic membranes). This review summarizes information related to the biological roles of uterine glands and their secretions in uterine receptivity, blastocyst/conceptus survival and implantation, and stromal cell decidualization. Studies with the ovine uterine gland knockout (UGKO) model support a primary role for uterine glands and, by inference, their secretions present in uterine luminal fluid histrotroph for conceptus survival and development. In rodents, studies with mutant and progesterone-induced UGKO mice found that uterine glands and their secretions are unequivocally required for establishment of uterine receptivity and blastocyst implantation and also may influence blastocyst trophectoderm activation and stromal cell decidualization in the uterus. Similarly in humans, histotroph from uterine glands appears critical for blastocyst implantation, uterine receptivity, and conceptus nutrition during the first trimester and uterine glands likely have a role in stromal cell decidualization. An increased understanding of uterine gland biology is important for diagnosis, prevention and treatment of fertility problems, particularly infertility and recurrent pregnancy loss, in domestic animals and humans.
Keywords: uterus, gland, blastocyst, implantation, decidualization, pregnancy
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EHU/UPV/UBC - The International Journal of Developmental Biology 58: 117-126 (2014)
doi: 10.1387/ijdb.130335gw / © UBC Press (www.a360grados.net)
Evolution of mammalian pregnancy and the origin of the decidual stromal cell
Günter P. Wagner 1,2, Koryu Kin 1, Louis Muglia 3 and Mihaela Pavličev 3
1. Department of Ecology and Evolutionary Biology and Systems Biology Institute, Yale University, New Haven, CT, USA
2. Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA
3. Cincinnati Children’s Hospital, University of Cincinnati, OH, USA
ABSTRACT: Reproduction in eutherian mammals is characterized by extended intrauterine retention of the fetus after implantation. We summarize evolutionary innovations that enable this form of vivipary, including early maternal recognition of pregnancy, invasive placentation, and emergence of the decidual cell type. We first review the structure of the marsupial endometrium and its relationship to that of eutherian mammals. While the tissue components of endometrium are the same in marsupials and eutherians, an important difference is the amount of stromal cells, which are much more abundant in eutherians. Moreover, the nature of the invasive placentation differs in marsupials and eutherians. In the opossum, it consists of cytoplasmatic extensions of trophoblast cells that penetrate between the luminal epithelial cells to contact maternal capillaries. In bandicoots, the trophoblast and luminal epithelial cells fuse, and the maternal epithelium is replaced by a layer of multinucleated cells. In no case has there been evidence of a direct interaction between trophoblast and stromal cells. The direct interface between the trophoblast and maternal stroma is a derived feature of eutherian mammals, coincidental with the origin of decidual cells. Gene expression studies are suggestive of “categorical reprograming” of endometrial fibroblasts during decidualization. This reprogramming suggests that the decidual cell is a distinct cell type rather than a modulation of endometrial fibroblasts. Further support for this hypothesis is the origin of derived transcription factor interactions that are necessary for the regulation of decidual gene expression, in particular the interactions between HOXA11 and CEBPB with FOXO1A.
Keywords: evolution of pregnancy, decidual cell, cell type evolution, viviparity, marsupial pregnancy
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EHU/UPV/UBC - The International Journal of Developmental Biology 58: 127-137 (2014)
doi: 10.1387/ijdb.130340pd / © UBC Press (www.a360grados.net)
Transcriptomics of the human endometrium
Patricia Díaz-Gimeno 1, Maria Ruíz-Alonso 2, David Blesa 1,2 and Carlos Simón 1,2,3
1. Fundación Instituto Valenciano de Infertilidad (FIVI), Valencia University and Instituto Universitario IVI/INCLIVA, Spain
2. IVIOMICS, Parc Cientific Valencia University, Paterna, Valencia, Spain
3. Department of Ob/Gyn, Stanford University School of Medicine, Stanford University, CA, USA
ABSTRACT: During the mid-secretory phase, the endometrium acquires the receptive phenotype, which corresponds to the only period throughout the endometrial cycle in which embryo implantation is viable. Endometrial receptivity is a crucial process and even more important in Assisted Reproductive Technologies (ART) where embryo-endometrial synchronization is coordinated through embryo transfer timing. Over the last decade, transcriptomic analyses performed on the human endometrium have shown that specific genomic signatures can be used to successfully phenotype different phases of the menstrual cycle including the receptive stage, independently of the histological appereance of the endometrial tissue. In this paper, we review current evidence demonstrating that endometrial transcriptomics objectively identifies the implantation window in a personalized manner, opening the field for the diagnosis of the endometrial factor in ART and moving to stratified medicine at this level, using microarray technology and soon high-throughput next generation sequencing coupled with functional and systems genomics approach.
Keywords: Endometrial Receptivity Array, personalised embryo transfer, personalised window of implantation, clinical translation, systems biology
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EHU/UPV/UBC - The International Journal of Developmental Biology 58: 139-146 (2014)
doi: 10.1387/ijdb.130348mb / © UBC Press (www.a360grados.net)
Role of uterine stromal-epithelial crosstalk in embryo implantation
Alison M. Hantak 1, Indrani C. Bagchi 2 and Milan K. Bagchi 1
1. Departments of Molecular & Integrative Physiology
2. Comparative Biosciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA
ABSTRACT: Embryo implantation is a crucial step for successful pregnancy. Prior to implantation, the luminal epithelium undergoes steroid hormone-induced structural and functional changes that render it competent for embryo attachment. Subsequent invasion of the embryo into the maternal tissue triggers differentiation of the underlying stromal cells to form the decidua, a transient tissue which supports the developing embryo. Many molecular cues of both stromal and epithelial origin have been identified that are critical mediators of this process. An important aspect of uterine biology is the elaborate crosstalk that occurs between these tissue compartments during early pregnancy through expression of paracrine factors regulated by the steroid hormones estrogen and progesterone. Aberrant expression of these factors often leads to implantation failure and infertility. Genetically-engineered mouse models have been instrumental in elucidating what these paracrine factors are, what drives their expression, and what their effects are on neighboring cells. This review provides an overview of several well-characterized signaling pathways that span both epithelial and stromal compartments and their function during implantation in the mouse.
Keywords: steroid hormone, uterine receptivity, uterine proliferation, uterine differentiation, pregnancy
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EHU/UPV/UBC - The International Journal of Developmental Biology 58: 147-154 (2014)
doi: 10.1387/ijdb.130345wh / © UBC Press (www.a360grados.net)
Molecular determinants of uterine receptivity
Zhaowei Tu 1,2, Hao Ran 1,3, Shuang Zhang 1, Guoliang Xia 3, Bingyan Wang 1 and Haibin Wang 1
1. State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences
2. Graduate School of the Chinese Academy of Sciences
3. State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, PR China
ABSTRACT: Uterine receptivity is defined as a limited period when the uterine environment is conducive to blastocyst acceptance and implantation. Any disturbance of this early pregnancy event will compromise pregnancy success. In this review, we first briefly summarize uterine morphological coordination for the attainment of receptivity, then focus on elucidating the molecular complexity in establishing uterine receptivity and hence embryo implantation. A better understanding of the molecular basis governing uterine receptivity will help to improve the outcome of natural pregnancy and pregnancy conceived via assisted reproductive techniques.
Keywords: uterine receptivity, molecular determinants
Embryo-uterine interactions ---------------------------------------------------
EHU/UPV/UBC - The International Journal of Developmental Biology 58: 155-161 (2014)
doi: 10.1387/ijdb.140020dw / © UBC Press (www.a360grados.net)
The evolution of embryo implantation
Michael R. McGowen 1, Offer Erez 2, Roberto Romero 3,4,5 and Derek E. Wildman 1,3,4,6
1. Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, USA
2. Department of Obstetrics and Gynecology, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel
3. Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD and Detroit, MI USA
4. Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA
5. Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, USA
6. Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
ABSTRACT: Embryo implantation varies widely in placental mammals. We review this variation in mammals with a special focus on two features: the depth of implantation and embryonic diapause. We discuss the two major types of implantation depth, superficial and interstitial, and map this character on a well-resolved molecular phylogenetic tree of placental mammals. We infer that relatively deep interstitial implantation has independently evolved at least eight times within placental mammals. Moreover, the superficial type of implantation represents the ancestral state for placental mammals. In addition, we review the genes involved in various phases of implantation, and suggest a future direction in investigating the molecular evolution of implantation-related genes.
Keywords: mammal, phylogeny, gene, implantation, superficial, interstitial
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EHU/UPV/UBC - The International Journal of Developmental Biology 58: 163-174 (2014)
doi: 10.1387/ijdb.140074bm / © UBC Press (www.a360grados.net)
Embryonic diapause: development on hold
Jane C. Fenelon, Arnab Banerjee and Bruce D. Murphy
Centre de Recherche en Reproduction Animale, Université de Montréal, St-Hyacinthe QC Canada
ABSTRACT: Embryonic diapause, the temporary suspension of development of the embryo, is a fascinating reproductive strategy that has been frequently exploited across the animal kingdom. It is characterized by an arrest in development that occurs at the blastocyst stage in over 130 species of mammals. Its presumed function is to uncouple mating from parturition, to ensure that both occur at the most propitious moment for survival of the species. Diapause can be facultative, i.e. induced by physiological conditions, or obligate, i.e. present in every gestation of a species. In the latter case, the proximal signals for regulation are related to photoperiod. Three diverse models, the mouse, the mustelid carnivores and the wallaby have been studied in detail. From these studies it can be discerned that, although the endocrine cues responsible for induction of diapause and re-initiation of development vary widely between species, there are a number of commonalities. Evidence to date indicates that the uterus exercises the proximal regulatory influence over whether an embryo enters into and when it exits from diapause. Some factors have been identified that appear crucial to this regulation, in particular, the polyamines. Recent studies indicate that diapause can be induced in species where it does not exist in nature. This suggests that the potential for diapause in mammals to be due to a single evolutionary event, to which control mechanisms adapted when the trait was beneficial to reproductive success. Further work at the molecular, cellular and organismic levels will be required before the physiological basis of diapause is resolved.
Keywords: blastocyst, diapause, polyamine, evolutionary strategy
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EHU/UPV/UBC - The International Journal of Developmental Biology 58: 175-181 (2014)
doi: 10.1387/ijdb.140059mr / © UBC Press (www.a360grados.net)
Embryo-endometrial interactions during early development after embryonic diapause in the marsupial tammar wallaby
Marilyn B. Renfree and Geoff Shaw
Department of Zoology, The University of Melbourne, Victoria, Australia
ABSTRACT: The marsupial tammar wallaby has the longest period of embryonic diapause of any mammal. Reproduction in the tammar is seasonal, regulated by photoperiod and also lactation. Reactivation is triggered by falling daylength after the austral summer solstice in December. Young are born late January and commence a 9-10-month lactation. Females mate immediately after birth. The resulting conceptus develops over 6- 7 days to form a unilaminar blastocyst of 80-100 cells and enters lactationally, and later seasonally, controlled diapause. The proximate endocrine signal for reactivation is an increase in progesterone which alters uterine secretions. Since the diapausing blastocyst is surrounded by the zona and 2 other acellular coats, the mucoid layer and shell coat, the uterine signals that maintain or terminate diapause must involve soluble factors in the secretions rather than any direct cellular interaction between uterus and embryo. Our studies suggest involvement of a number of cytokines in the regulation of diapause in tammars. The endometrium secretes platelet activating factor (PAF) and leukaemia inhibitory factor, which increase after reactivation. Receptors for PAF are low on the blastocyst during diapause but are upregulated at reactivation. Conversely, there is endometrial expression of the muscle segment homeobox gene MSX2 throughout diapause, but it is rapidly downregulated at reactivation. These patterns are consistent with those observed in diapausing mice and mink after reactivation, despite the very different patterns of endocrine control of diapause in these 3 divergent species. These common patterns suggest a similar underlying mechanism for diapause, perhaps common to all mammals, but which is activated in only a few.
Keywords: embryonic diapause, marsupial, MSX, PAF, LIF
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EHU/UPV/UBC - The International Journal of Developmental Biology 58: 183-187 (2014)
doi: 10.1387/ijdb.130337hl / © UBC Press (www.a360grados.net)
Evolving tales of autophagy in early reproductive events
Hyunjung J. Lim 1 and Haengseok Song 2
1. Department of Biomedical Science and Technology, Institute of Biomedical Science and Technology, Konkuk University, Gwangjin-gu
2. Department of Biomedical Science, College of Life Science, CHA University, Seoul, Korea
ABSTRACT: 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.
Keywords: autophagy, oocyte, sperm, embryo
Maternal immune/inflammatory cells and the establishment of pregnancy ------------
EHU/UPV/UBC - The International Journal of Developmental Biology 58: 189-198 (2014)
doi: 10.1387/ijdb.140054ae / © UBC Press (www.a360grados.net)
T cell behavior at the maternal-fetal interface
Patrice Nancy 1 and Adrian Erlebacher 1,2
1. Department of Pathology and 2. NYU Cancer Institute, NYU School of Medicine, New York, USA
ABSTRACT: Understanding the function of T cells at the maternal-fetal interface remains one of the most difficult problems in reproductive immunology. A great deal of work over the last two decades has led to the view that the T cells that populate the decidua have important roles in both normal and pathological pregnancies, but the exact nature of these roles has remained unclear. Indeed, the old assumption that decidual T cells are uniformly threatening to fetal survival because the placenta is fundamentally an ‘allograft’ has given way to the idea that different T cell subsets contribute in different ways to pregnancy success or failure. Accordingly, some T cells are thought to protect the placenta from immune rejection and facilitate embryo implantation, while others are thought to contribute to pregnancy pathologies such as preeclampsia and spontaneous abortion. Here, we review the current state of information on the behavior of decidual T cells with a focus on both mouse and human studies, and with an emphasis on the many unresolved areas within this overall emerging framework.
Keywords: Fetomaternal tolerance, pregnancy, decidua, placenta, antigen presentation
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EHU/UPV/UBC - The International Journal of Developmental Biology 58: 199-204 (2014)
doi: 10.1387/ijdb.140032kc / © UBC Press (www.a360grados.net)
Uterine natural killer cells as modulators of the maternal-fetal vasculature
Brooke C. Matson 1 and Kathleen M. Caron 1,2
1. Departments of Cell Biology & Physiology and 2. Genetics, University of North Carolina at Chapel Hill, North Carolina, USA
ABSTRACT: Precise and local control of the innate immune system within the placenta is an essential component for achieving a normal and healthy pregnancy. One of the most abundant immune cells of the placenta is a subpopulation of natural killer (NK) cells that profusely populates the uterine decidua during early pregnancy. Uterine NK (uNK) cells and trophoblast cells of the placenta communicate both directly and indirectly to contribute to the critical process of spiral artery remodeling. Here, we discuss recent findings that expand our knowledge of uNK cell-trophoblast cell crosstalk and the important role it plays in the maternal vascular adaptation to pregnancy.
Keywords: NK cell, trophoblast cell, placenta, spiral artery remodeling, preeclampsia
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EHU/UPV/UBC - The International Journal of Developmental Biology 58: 205-217 (2014)
doi: 10.1387/ijdb.140096sr / © UBC Press (www.a360grados.net)
Immunological determinants of implantation success
Sarah A. Robertson and Lachlan M. Moldenhauer
Robinson Research Institute and School of Paediatrics and Reproductive Health, University of Adelaide, Australia
ABSTRACT: The capacity of the immune system to maintain the integrity of the individual requires recognition and control of entities identified as genetically distinct, or ‘non-self’. In mammalian reproduction, the embryo and subsequent fetus and placenta are all recognized as non-self by the maternal immune system, and are vulnerable to immunological attack. An active system to prevent rejection must exist from when conceptus and maternal tissues first come into contact at implantation. Crucial mediators of immune protection are inducible regulatory T cells (Treg cells). Unless sufficient Treg cells are present in the endometrium, successful implantation and progression to pregnancy cannot ensue. This key role of Treg cells confers to the female immune system substantial capability to influence reproductive events, particularly around the time of conception and embryo implantation. While on the one hand this risks susceptibility to immune-based reproductive disorders, the potential evolutionary trade-off is the benefit of quality control to avoid poor reproductive outcomes. Here we summarize current knowledge of the factors required to establish a robust Treg cell response and an immune environment conducive to successful implantation and pregnancy. These factors include (a) appropriate cytokine balance; (b) correct phenotype of endometrial leukocytes to enable Treg cell activation; (c) sufficient estrogen and progesterone to stabilize and strengthen Treg cell phenotype, and (d) appropriate priming of Treg cell populations by male partner seminal fluid. Compromises in the quality of this immune adaptation at conception can influence the early embryo and either prevent implantation or impair placental morphogenesis. Failure to successfully establish Treg cell-mediated immune tolerance can result in poor fertility or impart long-term adverse consequences for the fetus and offspring.
Keywords: cytokine, dendritic cell, immune tolerance, infertility, macrophage, natural killer cell, placenta, pregnancy, regulatory T cells, seminal fluid, uterus
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EHU/UPV/UBC - The International Journal of Developmental Biology 58: 219-229 (2014)
doi: 10.1387/ijdb.140109ss / © UBC Press (www.a360grados.net)
Natural killer cells and regulatory T cells in early pregnancy loss
Surendra Sharma
Women and Infants Hospital of Rhode Island, Warren Alpert Medical School of Brown University, Department of Pediatrics, Providence, Rhode Island, USA
ABSTRACT: Survival of the allogeneic embryo in the uterus depends on the maintenance of immune tolerance at the maternal-fetal interface. The pregnant uterus is replete with activated maternal immune cells. How this immune tolerance is acquired and maintained has been a topic of intense investigation. The key immune cells that predominantly populate the pregnant uterus are natural killer (NK) cells. In normal pregnancy, these cells are not killers, but rather provide a microenvironment that is pregnancy compatible and supports healthy placentation. In placental mammals, an array of highly orchestrated immune elements to support successful pregnancy outcome has been incorporated. This includes active cooperation between maternal immune cells, particularly NK cells, and trophoblast cells. This intricate process is required for placentation, immune regulation and to remodel the blood supply to the fetus. During the past decade, various types of maternal immune cells have been thought to be involved in cross-talk with trophoblasts and in programming immune tolerance. Regulatory T cells (Tregs) have attracted a great deal of attention in promoting implantation and immune tolerance beyond implantation. However, what has not been fully addressed is how this immune-trophoblast axis breaks down during adverse pregnancy outcomes, particularly early pregnancy loss, and in response to unscheduled inflammation. Intense research efforts have begun to shed light on the roles of NK cells and Tregs in early pregnancy loss, although much remains to be unraveled in order to fully characterize the mechanisms underlying their detrimental activity. An increased understanding of host-environment interactions that lead to the cytotoxic phenotype of these otherwise pregnancy compatible maternal immune cells is important for prediction, prevention and treatment of pregnancy maladies, particularly recurrent pregnancy loss. In this review, we discuss relevant information from experimental and human models that may explain the pregnancy disrupting roles of these pivotal sentinel cells at the maternal-fetal interface.
Keywords: pregnancy, immune tolerance, inflammation/infection, NK cell, Treg
Trophoblast development and actions on the maternal interface -----------------------
EHU/UPV/UBC - The International Journal of Developmental Biology 58: 231-238 (2014)
doi: 10.1387/ijdb.140053st / © UBC Press (www.a360grados.net)
DNA methylation and its role in the trophoblast cell lineage
Satoshi Tanaka, Momo O. Nakanishi1 and Kunio Shiota
Laboratory of Cellular Biochemistry, Department of Animal Resource Sciences/Veterinary Medical Sciences, The University of Tokyo, Tokyo, Japan
ABSTRACT: DNA methylation functions as cellular memory beyond generations of cells and is involved in many biological processes. Because of its relatively stable nature compared with the transcriptome, the DNA methylation profile of cells can also be used to evaluate developmental similarity and cellular phenotypes. Recent insights into 5-hydroxymethylcytosine have started to reshape our view of the epigenetic regulation of mammalian development. Both global DNA methylation and hydroxymethylation levels change dynamically during preimplantation embryogenesis. It is known that DNA methylation plays an essential role in embryonic cell fate restriction, whereas its role in trophoblast development requires further research. Two distinct blastocyst-derived stem cell lines, embryonic stem (ES) cells and trophoblast stem (TS) cells, are used to study the epigenetic mechanisms underlying cell lineage maintenance and the regulation of cell differentiation. Such studies will allow us to understand the details of the epigenetic landscape of trophoblast development, which should offer valuable information for managing pregnancy-related diseases in humans.
Keywords: DNA methylation, blastocyst, ICM, TE, TS cell
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EHU/UPV/UBC - The International Journal of Developmental Biology 58: 239-246 (2014)
doi: 10.1387/ijdb.130341mp / © UBC Press (www.a360grados.net)
BMP4 regulation of human trophoblast development
Yingchun Li 1,2 and Mana M. Parast 1,2
1. Department of Pathology and 2. Sanford Consortium for Regenerative Medicine, University of California San Diego, La Jolla, CA
ABSTRACT: Since the derivation of human embryonic stem cells, and the subsequent generation of induced pluripotent stem cells, there has been much excitement about the ability to model and evaluate human organ development in vitro. The finding that these cells, when treated with BMP4, are able to generate the extraembryonic cell type, trophoblast, which is the predominant functional epithelium in the placenta, has not been widely accepted. This review evaluates this model, providing comparison to early known events during placentation in both human and mouse and addresses specific challenges. Keeping in mind the ultimate goal of understanding human placental development and pregnancy disorders, our aim here is two-fold: to distinguish gaps in our knowledge arising from mis- or over-interpretation of data, and to recognize the limitations of both mouse and human models, but to work within those limitations towards the ultimate goal.
Keywords: trophoblast, placenta, BMP4, stem cells
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EHU/UPV/UBC - The International Journal of Developmental Biology 58: 247-259 (2014)
doi: 10.1387/ijdb.140083ms / © UBC Press (www.a360grados.net)
Adaptive mechanisms controlling uterine spiral artery remodeling during the establishment of pregnancy
Michael J. Soares, Damayanti Chakraborty, Kaiyu Kubota, Stephen J. Renaud and M.A. Karim Rumi
Institute for Reproductive Health and Regenerative Medicine, Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA
ABSTRACT: Implantation of the embryo into the uterus triggers the initiation of hemochorial placentation. The hemochorial placenta facilitates the acquisition of maternal resources required for embryo/fetal growth. Uterine spiral arteries form the nutrient supply line for the placenta and fetus. This vascular conduit undergoes gestation stage-specific remodeling directed by maternal natural killer cells and embryo-derived invasive trophoblast lineages. The placentation site, including remodeling of the uterine spiral arteries, is shaped by environmental challenges. In this review, we discuss the cellular participants controlling pregnancy-dependent uterine spiral artery remodeling and mechanisms responsible for their development and function.
Keywords: hemochorial placentation, natural killer cell, trophoblast, PI3K/AKT, FOSL1, hypoxia, NOTCH, STOX1
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EHU/UPV/UBC - The International Journal of Developmental Biology 58: 261-271 (2014)
doi: 10.1387/ijdb.140011da / © UBC Press (www.a360grados.net)
Cell signaling in trophoblast-uterine communication
Rani Fritz 1,2 Chandni Jain 1,2 and D. Randall Armant 1,3,4
Departments of 1. Obstetrics and Gynecology, 2. Physiology and 3. Anatomy and Cell Biology, Wayne State University, C.S. Mott Center for Human Growth and Development, Detroit, Michigan and 4. Program in Reproductive and Adult Endocrinology, NICHD, NIH, DHHS, Bethesda, Maryland, USA
ABSTRACT: Intricate and precise communication between the blastocyst and the uterus orchestrates embryo implantation. However, many questions remain unanswered regarding the molecular complexities of implantation. On-time implantation requires a receptive uterus and a mature blastocyst with trophoblast cells capable of adhering to and invading the endometrium. Defects in uterine receptivity or embryo/uterine signaling can cause implantation failure or early pregnancy loss, whereas deficient trophoblast differentiation can generate placental abnormalities that produce adverse pregnancy outcomes. This review will discuss several examples of signaling pathways that regulate trophoblast and uterine development during this period. Leukemia inhibitory factor is involved in uterine priming for implantation. The epidermal growth factor signaling system contributes to trophoblast-uterine communication, as well as trophoblast adhesion and invasion. Indian hedgehog signaling synchronizes tissue compartments within the uterus, and WNT signaling mediates numerous interactions within the implantation site and developing placenta. The autocrine, paracrine and juxtacrine interactions mediated by these signaling pathways contribute significantly to the establishment of pregnancy, although there are many other known and yet to be discovered factors that synchronize the maternal and embryonic developmental programs.
Keywords: growth factor, trophoblast, endometrium, blastocyst, signaling
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EHU/UPV/UBC - The International Journal of Developmental Biology 58: 273-280 (2014)
doi: 10.1387/ijdb.130329gd / © UBC Press (www.a360grados.net)
Pregnancy-specific glycoproteins: complex gene families regulating maternal-fetal interactions
Tom Moore 1 and Gabriela S. Dveksler 2
1. School of Biochemistry and Cell Biology, Western Gateway Building, University College Cork, Cork, Ireland
2. Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
ABSTRACT: The pregnancy-specific glycoproteins (PSGs) are the most abundant trophoblastic proteins in maternal blood during human pregnancy and they appear to be exclusive to species with hemochorial placentation. There are ten protein-coding human PSG genes (PSG1 - PSG9, PSG11) and also multiple PSG genes in non-human primates, rodents and bats. Several studies indicate that PSGs have immunoregulatory, pro-angiogenic, and anti-platelet functions. Some PSGs have been shown to bind different moieties on the surface of cells, including the tetraspanin CD9, heparan sulphate, and specific integrins. Recently, PSG1 was shown to associate with and activate the anti-inflammatory cytokines transforming growth factor (TGF)-β1 and TGF- β2 making PSG1 one of the few known biological activators of these important cytokines. TGF-βs regulate many biological processes essential for pregnancy success including trophoblast invasion and proliferation, angiogenesis, extracellular matrix formation and tolerance to the fetal semi-allograft. As summarized in this review, progress has been made in recent years towards a better understanding of the functions of these proteins which were originally described in the early 1970s, but more research will likely contribute to demonstrate their importance for a successful pregnancy.
Keywords: Trophoblast, Placental hormone, Immunoregulation, TGFβ, Integrin
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EHU/UPV/UBC - The International Journal of Developmental Biology 58: 281-289 (2014)
doi: 10.1387/ijdb.130349ys / © UBC Press (www.a360grados.net)
The role of trophoblastic microRNAs in placental viral infection
Jean-Francois Mouillet 1, Yingshi Ouyang 1, Avraham Bayer 1,2, Carolyn B. Coyne 2,1, and Yoel Sadovsky 1,2
1. Magee-Womens Research Institute, Department of Obstetrics, Gynecology and Reproductive Sciences and 2. Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
ABSTRACT: During the past decade, various types of small non-coding RNAs were found to be expressed in all kingdoms and phyla of life. Intense research efforts have begun to shed light on their biological functions, although much remains to be determined in order to fully characterize their scope of biological action. Typically, small RNAs provide sequence specificity to a protein complex that is driven to silence a long target RNA. MicroRNAs (miRNAs) are small RNAs that are coded in the genome of most eukaryotes, and contribute to the cellular identity by regulating cell-specific gene networks by translational repression or degradation of mRNA. These effects commonly fine-tune gene expression associated with developmental or environmental cues. Different cell types can be characterized by their distinctive cellular miRNA landscape. The human placenta expresses a unique set of miRNAs, a high proportion of which is derived from a large cluster located on chromosome 19, (termed chromosome 19 miRNA cluster, or C19MC). Interestingly, a fraction of these placenta-enriched miRNAs are released to the extracellular environment through exosomes that were recently found to induce an antiviral immunity. In this review, we explore relevant placental viral infections and discuss the antiviral role of exosome-packaged placental C19MC miRNAs in this context.
Keywords: trophoblast, virus, C19MC, trophomiR, exosomes
Epigenetics, development and disease -------------------------------------
EHU/UPV/UBC - The International Journal of Developmental Biology 58: 291-298 (2014)
doi: 10.1387/ijdb.140077mb / © UBC Press (www.a360grados.net)
Epigenetics and imprinting in human disease
Jennifer M. Kalish, Connie Jiang and Marisa S. Bartolomei
Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA
ABSTRACT: Most genes are expressed from both parental chromosomes; however, a small number of genes in mammals are imprinted and expressed in a parent-of-origin specific manner. These imprinted genes play an important role in embryonic and extraembryonic growth and development, as well as in a variety of processes after birth. Many imprinted genes are clustered in the genome with the establishment and maintenance of imprinted gene expression governed by complex epigenetic mechanisms. Dysregulation of these epigenetic mechanisms as well as genomic mutations at imprinted gene clusters can lead to human disease.
Keywords: genomic imprinting, DNA methylation, Beckwith-Wiedemann syndrome, Russell-Silver syndrome
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