ContentsEmbryonic diapause is an evolutionary strategy by which a reversible arrest in embryo development occurs. In its two forms, facultative and obligate, it assures that offspring are born when optimal maternal and environmental conditions are present to ensure maximal survival. We have explored obligate delayed implantation in the mink (Neovison vison) over four decades: first by evaluation of the environmental regulation, then by determination of the pituitary factors that maintain diapause and provoke implantation followed by exploration of the ovarian contribution to the process. As the uterine environment is the proximal regulator of diapause, we employed a strategy of global gene analysis to discover differentially expressed pathways during embryo arrest and reactivation. These trials revealed that the synthesis of polyamines was increased in the uterus with reactivation of the embryo in vivo. Subsequent experiments demonstrated that the polyamine, putrescine, was capable of inducing escape of the embryo from obligate diapause, providing strong evidence that the paucity of polyamines induces developmental arrest, and reactivation is coupled to renewed uterine and/or embryonic synthesis of these polycations.
ContentsEmbryonic diapause is an evolutionary strategy to ensure that offspring are born when maternal and environmental conditions are optimal for survival. In many species of carnivores, obligate embryonic diapause occurs in every gestation. In mustelids, the regulation of diapause and reactivation is influenced by photoperiod, which then acts to regulate the secretion of pituitary prolactin. Prolactin in turn regulates ovarian steroid function. Reciprocal embryo transplant studies indicate that this state of embryonic arrest is conferred by uterine conditions and is presumed to be due to a lack of specific factors necessary for continued development. Studies of global gene expression in the mink (Neovison vison) revealed reduced expression of a cluster of genes that regulate the abundance of polyamines in the uterus during diapause, including the rate-limiting enzyme in polyamine production, ornithine decarboxylase (ODC). In addition, in this species, in vivo inhibition of the conversion of ornithine to the polyamine, putrescine, induces a reversible arrest in embryonic development and an arrest in both trophoblast and inner cell mass proliferation in vitro. Putrescine, at 0.5, 2 and 1,000 μM concentrations induced reactivation of mink embryos in culture, indicated by an increase in embryo volume, observed within five days. Further, prolactin induces ODC1 expression in the uterus, thereby regulating uterine polyamine levels. These results indicate that pituitary prolactin acts on ovarian and uterine targets to terminate embryonic diapause. In summary, our findings suggest that the polyamines, with synthesis under the control of pituitary prolactin, are the uterine factor whose absence is responsible for embryonic diapause in mustelid carnivores.Centre de recherche en reproduction animale, Faculté de médecine vétérinare,
Mink ovariectomized 14 days after the first of two matings received injections of 2 mg MPA, the same MPA treatment + an oestradiol-17 beta implant or no replacement therapy. Some mink were ovariectomized after implantation and given a single dose of 2 mg MPA or no replacement therapy. MPA persisted in the serum at detectable levels for 13 or more days in all mink treated. MPA and MPA + oestradiol induced uterine growth but neither treatment was capable of inducing embryo implantation. More embryos were retained in mink treated with MPA alone and these appeared to be viable. Implanted embryos persisted for a longer period in animals that were ovariectomized and treated with MPA. MPA neither supported pregnancy nor permitted parturition. Serum LH was elevated by 1 week after ovariectomy and elevations persisted for a further 20 or more days. While MPA alone had no apparent negative feedback effects on LH, animals that received MPA + oestradiol did not display any elevation of LH, suggesting that oestradiol or a combination of MPA and oestradiol has a potent negative feedback in mink.
The phenomenon of obligate embryonic diapause, comprising developmental arrest at the blastocyst stage, has been recognized to occur in more than 60 species in three families in the Order Carnivora. The evolutionary advantage believed to be conferred by this trait is that it permits mating and parturition to occur at the most favorable times of year for reproductive success and offspring survival. The carnivore blastocyst in diapause consists of hundreds of cells, configured in the classic mammalian compartments of inner cell mass and trophoblast. It is encapsulated in a glycoprotein coat, derived, at least in part, from the zona pellucida of the parent oocyte. The temporal uncoupling of mating from parturition is regulated by changes in the annual photoperiod, mediated through the pineal gland, pars tuberalis a pars distalis of the pituitary and thyroid glands. In the best-studied species, the pituitary signal that awakes the embryo from arrest is prolactin, acting on the ovary and on the uterus. Ovarian signals, other than progesterone are not well understood, but it appears that there is an ovarian peptide essential for the reactivation of the embryo in mink. New studies have identified the uterine signals in the mink, and it has been shown that the synthesis and secretion of polyamines activates the mink embryo from diapause. While extensive progress has been made, it is not clear whether the regulatory mechanisms that have been identified in the better-known species are universal to carnivore diapause. As many of the carnivore species are endangered, further research on diapause is essential to their survival.
Summary ― We have established a dispersed bovine pituitary cell culture system to study the effects of charcoal-extracted bovine follicular fluid (BFF) or bovine inhibin, partially purified by immunoaffinity chromatography (IPI), on the spontaneous release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Pituitary cells were plated at 0.25, 0.5 or 1 x 10 6 viable cells/well (c/w) and incubated for 48 h. The medium was replaced and BFF (0, 0.54, 2.7, 13.7, 68.7 (0, 0,54, 2,7, 13,7, 68,7
Embryonic diapause was first identified over 150 years ago, but many questions still remain about how the external and hormonal controls of embryonic diapause translate into how the uterus conveys information to the embryo. Current evidence suggests that the control of diapause is mediated by components of the uterine secretions. However, the identity of the essential signalling molecule(s) is unknown. The mouse (Mus musculus), the mink (Neovison vison) and the tammar wallaby (Macropus eugenii) are the three most extensively studied mammalian diapause species. Despite differences in the external and hormonal control of diapause between these three species, we have now found that there is conservation of numerous molecular factors around diapause and reactivation. This was first suggested via the conserved expression of various growth factors. The first evidence for a conserved mechanism resulted from a study on the muscle segment homeobox transcription factor (MSX) in the uterus during diapause, whose expression is conserved amongst the mouse, mink and wallaby. Following this was the evidence that inhibition of polyamines induces entry into diapause in both the mink and mouse. Thus, although the signalling mechanisms via which the uterus is induced into diapause vary amongst species, the molecular communication that occurs between the uterus and the embryo to control diapause is conserved. Given that these mechanisms are conserved across varying taxa, this implies a universal mechanism for maintaining embryo health amongst all mammals. New technologies are now allowing us to examine diapause from a global perspective and to increase our knowledge of this enigmatic stage of pregnancy.
The capacity of the mammalian embryo to arrest development during early gestation is a topic that has fascinated biologists for over 150 years. The first known observation of this phenomenon was in a ruminant, the roe deer (Capreolus capreolus) in 1854, later confirmed in a number of studies in the last century [1]. The phenomenon, now known as embryonic diapause, was then found to be present in a wide range of species and across multiple taxa. Since that time, its biological mystery has attracted studies by scientists from around the globe.
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