Cadence of procreation: Orchestrating embryo–uterine interactions

Abstract

Embryo implantation in eutherian mammals is a highly complex process and requires reciprocal communication between different cell types of the embryo at the blastocyst stage and receptive uterus. The events of implantation are dynamic and highly orchestrated over a species-specific period of time with distinctive and overlapping expression of many genes. Delayed implantation in different species has helped elucidate some of the intricacies of implantation timing and different modes of the implantation process. How these events are coordinated in time and space are not clearly understood. We discuss potential regulators of the precise timing of these events with respect to central and local clock mechanisms. This review focuses on the timing and synchronization of early pregnancy events in mouse and consequences of their aberrations at later stages of pregnancy.

Spatial and Temporal Analyses of FGF9 Expression During Early Pregnancy

“…The steroid hormones estrogen (E) and progesterone (P), through their cognate receptors estrogen receptor (ER) and progesterone receptor (PR), prepare the uterus for pregnancy [1, 2]. The transcriptional activity of PR and ER leads to the synthesis of cytokines, growth factors, lipid mediators, and genes that control the dynamics of uterine transition to a receptive state and the establishment of pregnancy [2, 3].…”

“…The transcriptional activity of PR and ER leads to the synthesis of cytokines, growth factors, lipid mediators, and genes that control the dynamics of uterine transition to a receptive state and the establishment of pregnancy [2, 3]. In mice, the window of uterine receptivity corresponds to the P-mediated downregulation of ER activity in the uterine luminal epithelium (LE).…”

Embryonic Diapause and Maternal Recognition of Pregnancy in Diapausing Mammals

“…Some of these presumably control the arrested growth that occurs in diapause. These include epidermal growth factor (EGF and HB-EGF), leukaemia inhibitory factor (LIF), insulin-like growth factor (IGF), platelet-derived growth factor (PDGF), fi broblast growth factor (FGF), platelet-activating factor (PAF), transforming growth factor β (TGF-β), interleukin-1ß (IL1B), bone morphogenic protein-2 (BMP2), prostaglandin synthetase PTGS2 (COX2), fi broblast growth factor (FGF), signalling molecules of the wingless (WNT) family and the transcriptional regulators Msx1 and Msx2 (Cha and Dey 2014 ). Many of these are also present in the blastocyst, and the expression of a number of them is now known to coincide with reactivation.…”

“…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 ). Msx and LIF interact, but in LIF knockout mice, Msx1 continues to be expressed (Cha et al 2013 ;Daikoku et al 2011 ).…”

“…Approximately 130 mammalian species have diapause, of which 38 are marsupial, but the morphological and molecular changes that take place during the onset and reactivation from diapause have been examined in very few (Fenelon et al 2014a ;Renfree and Calaby 1981 ). Rodents, especially the mouse, have been the primary model, but two other species, namely, the mink Mustela vison and the tammar wallaby Macropus eugenii have been extensively studied (Cha and Dey 2014 ;Dey and Lim 2006 ;Dey et al 2004 ;Fenelon et al 2014a ;Lopes et al 2006 ;Mead 1993 ;Murphy 2012a , b ;Shaw 2000 , 2014 ;Tyndale-Biscoe and Renfree 1987 ). Interestingly, the fi rst species in which diapause was recognised was the roe deer, Capreolus capreolus , but it is the only confi rmed ungulate with diapause although there have been suggestions that Pere David's deer ( Elaphurus davidianus ) also may have a period of diapause (Brinklow and Loudon 1993 ).…”