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

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.

Cancer metastasis: enactment of the script for human reproductive drama

“…Diapause is a common reproductive phenomenon which has been observed in many vertebrates including mammals [61, 62]. In diapause, an arriving embryo could hold off implantation for a considerably long period of time until ambient nutrients become abundant.…”

Embryonic Diapause and Maternal Recognition of Pregnancy in Diapausing Mammals

“…Interestingly, it appears that the function of Msx is to limit uterine stress-mediated infl ammatory responses and so to maintain diapause (Cha et al 2015 ). Msx1 and Msx2 are found in the uteri of mice, mink and tammar wallabies during embryonic diapause (Cha et al 2013 ;Fenelon et al 2014a ;Renfree and Shaw 2014 ). In mice without diapause, Msx expression is transient early on day 4pc, but during diapause, it is highly expressed, and in its absence, there is reduced blastocyst recovery and survival (Cha and Dey 2014 ;Cha et al 2013 ).…”

“…In the diapausing tammar embryo, PAF is low, but endometrial PAF increases around the time of reactivation (Fenelon et al 2014b ;Kojima et al 1993 ). It has a reciprocal expression pattern with MSX (Renfree and Shaw 2014 ). It is present in culture media from endometrial cultures and although variable appears to increase at the time when the fi rst mitoses are observed after blastocyst reactivation (Kojima et al 1993 ;Spindler et al 1996 ).…”

Regulation of Implantation and Establishment of Pregnancy in Mammals

“…Interestingly, it appears that the function of Msx is to limit uterine stress-mediated infl ammatory responses and so to maintain diapause (Cha et al 2015 ). Msx1 and Msx2 are found in the uteri of mice, mink and tammar wallabies during embryonic diapause Fenelon et al 2014a ;Renfree and Shaw 2014 ). In mice without diapause, Msx expression is transient early on day 4pc, but during diapause, it is highly expressed, and in its absence, there is reduced blastocyst recovery and survival .…”

“…In the diapausing tammar embryo, PAF is low, but endometrial PAF increases around the time of reactivation (Fenelon et al 2014b ;Kojima et al 1993 ). It has a reciprocal expression pattern with MSX (Renfree and Shaw 2014 ). It is present in culture media from endometrial cultures and although variable appears to increase at the time when the fi rst mitoses are observed after blastocyst reactivation (Kojima et al 1993 ;Spindler et al 1996 ).…”