Polyamines Are Implicated in the Emergence of the Embryo from Obligate Diapause

Lefèvre, Pavine; Palin, Marie‐France; Chen, Gary; Turecki, Gustavo; Murphy, Bruce D.

doi:10.1210/en.2010-0955

Cited by 52 publications

(55 citation statements)

References 46 publications

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“…Blockade of Odc1 conversion of ornithine to the polyamine putrescine by the suicide inhibitor difluoromethyl ornithine (DFMO) prevents implantation in the mouse (Zhao et al, 2008) and reversibly arrests development in mink (Lefevre et al, 2011b) and mouse (Zwierzchowski et al, 1986) embryos. Expression of ODC1, along with the polyamine availability genes (Lefevre et al, 2011a) and uterine content of the polyamine putrescine (Lefevre et al, 2011b), are upregulated at the termination of diapause in the mink (Murphy, 2012).…”

Section: The Uterus Dictates Diapausementioning

confidence: 99%

Embryonic diapause: development on hold

Fenelon

Banerjee²,

Murphy³

2014

Int. J. Dev. Biol.

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120

130

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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.

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Section: The Uterus Dictates Diapausementioning

confidence: 99%

Embryonic diapause: development on hold

Fenelon

Banerjee²,

Murphy³

2014

Int. J. Dev. Biol.

Self Cite

120

130

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“…Polyamines are another interesting group of molecules that indirectly regulate cell cycling and protein synthesis, and there is accumulating evidence that they may play a role in diapause. In the mink, genes that inhibit polyamine degradation are upregulated (Lefevre et al, 2011a, Lefevre et al, 2011b and the polyamine putrescine and its synthetic enzyme ornithine decarboxylase are expressed at the termination of diapause in the mink (Murphy, 2012). Further study of these and other numerous growth factors and cytokines will provide new evidence for the molecular control of embryonic diapause.…”

Section: Other Regulatory Factorsmentioning

confidence: 99%

Embryo-endometrial interactions during early development after embryonic diapause in the marsupial tammar wallaby

Renfree¹,

Shaw²

2014

Int. J. Dev. Biol.

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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.

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“…For example, Arg can be converted to ornithine by arginase and ornithine converted to putrescine, a polyamine, by ODC1 [16]. Polyamines stimulate proliferation and migration of trophectoderm cells and are required for the transition of mink blastocysts in delayed implantation to an activated state for expansion and implantation [17,18]. Arg can also be metabolized by NOS to NO that stimulates proliferation and migration of ovine trophectoderm cells [19].…”

Section: The Uterine Lumenal Microenvironment Derives From the Secretmentioning

confidence: 99%

Select Nutrients in the Uterine Lumen of Sheep and Pigs Affect Conceptus Development

Bazer

Kim

et al. 2012

J. Reprod. Dev.

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Abstract. Interferon tau (IFNT) is the pregnancy recognition signal from ruminant conceptuses. IFNT also acts with P4 to induce expression of genes for transport of nutrients, such as glucose (Gluc) and arginine (Arg) into the uterine lumen to activate mechanistic mammalian target of rapamycin (MTOR) cell signaling that stimulates proliferation, migration, gene transcription and mRNA translation by conceptus trophectoderm (Tr). In ewes, Arg and Gluc increase significantly in the uterine lumen between Days 10 and 15 of pregnancy due to increased expression of transporters for Gluc (SLC2A1 and SLC5A1) and Arg (SLC7A2B) by uterine epithelia. Arg and Gluc stimulate proliferation, migration and mRNA translation by Tr. Arg increases expression of GTP cyclohydrolase 1 (GCH1) and IFNT mRNAs while Arg and Gluc increase ornithine decarboxylase, nitric oxide synthase 2, and GCH1 mRNAs and proteins by Tr cells. GCH1 is required for synthesis of tetrahydrobiopterin, an essential cofactor for all NOS isoforms. Arg is metabolized to nitric oxide and polyamines that increase proliferation and migration of Tr cells. In pigs, Gluc, Arg, leucine (Leu) and glutamine (Gln) increase in the uterine lumen between Days 12 and 15 of pregnancy due to enhanced expression of transporters for Gluc and amino acids. Transporters for Gluc in porcine uterine LE (SLC2A1) and conceptus trophectoderm (SLC2A2) are abundant. Transporters for glutamate and neutral (SLC1A1, SLC1A4) and cationic (SLC7A1, SLC7A2, SLC7A7, SLC7A9) amino acids are expressed in uterine LE and SLC7A3 mRNA is expressed in conceptus Tr. Arg and Leu increase MTOR cell signaling and proliferation of pig Tr, as do Gluc and fructose. Azaserine, an inhibitor of hexosamine biosynthesis, inhibits effects of Gluc and fructose. Thus, select nutrients in the uterine lumen affect gene transcription and mRNA translation to affect conceptus development. Key words: Amino acids, Fructose, Glucose, Uterus conceptus development (J. Reprod. Dev. 58: [180][181][182][183][184][185][186][187][188] 2012) E stimates of embryonic death loss in mammals range from 20 to 40 percent and two-thirds of these losses occur during the peri-implantation period of pregnancy [1]. Establishment and maintenance of pregnancy requires appropriate development of the conceptus (embryo/fetus and its extra-embryonic membranes) for pregnancy recognition signaling to ensure maintenance of a functional corpus luteum (CL) to secrete progesterone (P4) that is required for an intrauterine environment that supports implantation, placentation and uterine functions essential for successful outcomes of pregnancy [2]. Interactions among the conceptus and uterine cell types, especially luminal (LE), superficial glandular (sGE) and glandular (GE) epithelia and stromal cells (SC), are essential for conceptus development, signaling for maternal recognition of pregnancy, uterine blood flow, water and electrolyte movement, transport of sugars and amino acids into the uterine lumen, as well as secretion of proteins by uterine epithelia...

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Polyamines Are Implicated in the Emergence of the Embryo from Obligate Diapause

Cited by 52 publications

References 46 publications

Embryonic diapause: development on hold

Embryonic diapause: development on hold

Embryo-endometrial interactions during early development after embryonic diapause in the marsupial tammar wallaby

Select Nutrients in the Uterine Lumen of Sheep and Pigs Affect Conceptus Development

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