Embryonic Diapause: Advances in Understanding the Enigma of Seasonal Delayed Implantation

Abstract

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.

Embryonic diapause: development on hold

“…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).…”

“…Multiple studies have shown that implantation is preceded by a rapid increase in circulating progesterone from the reactivated corpus luteum (Stoufflet et al, 1989;Murphy, 2012). Prolactin binds to membrane preparations from the anestrous mink uterus (Rose et al, 1983).…”

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

“…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.…”

“…The ability to arrest embryonic development during the reproductive cycle is widespread amongst mammals (Lopes et al, 2004, Murphy, 2012, Renfree and Calaby, 1981, Renfree and Shaw, 2000. Embryonic diapause is a transient state in which embryos at the blastocyst stage are arrested in growth and metabolic activity in synchrony with uterine quiescence.…”

Artemin, a Diapause-Specific Chaperone, Contributes to the Stress Tolerance of Artemia Cysts and Influences Their Release from Females

“…Diapause, which is most common in insects (Poelchau et al, 2013;Mizoguchi et al, 2013;Fan et al, 2013) but occurs in organisms as diverse as rotifers (Clark et al, 2012), tardigrades (Guidetti et al, 2011), crustaceans (Tarrant et al, 2008;King and MacRae, 2012;Clark et al, 2013), killifish (Meller et al, 2012) and mammals (Murphy, 2012;Cha et al, 2013), entails decreased metabolism and augmentation of stress tolerance (Denlinger, 2002;Koštál, 2006;MacRae, 2010;Hahn and Denlinger, 2011). Photoperiod, temperature and crowding induce diapause, an integral part of the life cycle of many animals (Xiao et al, 2010;Meuti and Denlinger, 2013).…”