A new role for muscle segment homeobox genes in mammalian embryonic diapause

Abstract

Mammalian embryonic diapause is a phenomenon defined by the temporary arrest in blastocyst growth and metabolic activity within the uterus which synchronouslybecomes quiescent to blastocyst activation and implantation. Thisreproductive strategy temporally uncouples conception from parturition until environmental or maternal conditions are favourable for the survival of the mother and newborn. The underlying molecular mechanism by which the uterus and embryo temporarily achieve quiescence, maintain blastocyst survival and then resume blastocyst activation with subsequent implantation remains unknown. Here, we show that uterine expression of Msx1 or Msx2, members of an ancient, highly conserved homeobox gene family, persists inthree unrelated mammalian species during diapause, followed by rapid downregulation with blastocyst activation and implantation. Mice with uterineinactivation of Msx1 and Msx2 fail to achieve diapause and reactivation.Remarkably, the North American mink and Australian tammar wallaby sharesimilar expression patterns of MSX1 or MSX2 as in mice-it persists duringdiapause and is rapidly downregulated upon blastocyst activation and implantation. Evidence from mouse studies suggests that the effects of Msx genes indiapause are mediated through Wnt5a, a known transcriptional target of uterineMsx. These studies provide strong evidence that the Msx gene family constitutes a common conserved molecular mediator in the uterus duringembryonic diapause to improve female reproductive fitness. © 2013 The Authors.