NODAL signaling components regulate essential events in the establishment of pregnancy

Abstract

Successful mammalian reproduction is dependent on a receptive and nurturing uterine environment. In order to establish pregnancy in humans, the uterus must i) be adequately prepared to receive the blastocyst, ii) engage in a coordinated molecular dialog with the embryo to facilitate implantation, and iii) undergo endometrial decidualization. Although numerous factors have been implicated in these essential processes, the precise network of molecular interactions that govern receptivity, embryo implantation, and decidualization remain unclear. NODAL, a morphogen in the transforming growth factor b superfamily, is well known for its critical functions during embryogenesis; however, recent studies have demonstrated an emerging role for NODAL signaling during early mammalian reproduction. Here, we review the established data and a recent wave of new studies implicating NODAL signaling components in uterine cycling, embryo implantation, and endometrial decidualization in humans and mice.Reproduction (2013) 145 R55-R64

Interacción Endometrio Trofoblasto, en la Implantación Humana: Revisión de la Literatura

“…LEFTYA es otro morfógeno, descrito como antagónico a Nodal, que actúa como mediador de enzimas proteolíticas denominadas metaloproteinasas (MMP1, MMP3 y MMP9), que se relacionan con la degradación de la función uterina. De esta manera ambosmorfógenos se ven expresados a lo largo del ciclo endometrial en distintas concentraciones, con participación antagónicas durante este proceso (Park & Dufort, 2013).…”

TGFβ superfamily signaling and uterine decidualization

“…NODAL, a key regulator of embryogenesis, is implicated in several pregnancy-associated events, including implantation of blastocyst and uterine decidualization [ 55 ]. Deletion of Nodal in the mouse uterus using Pgr -Cre leads to fertility defects, accompanied by fetal loss and preterm birth due to intrauterine growth restriction and malformation of the decidua basalis [ 56 ].…”

“…Both activin A receptor type 1B (ACVR1B, known as ALK4) and ACVR1C (known as ALK7) mediate NODAL signaling that is essential for pregnancy [ 55 , 65 ]. Ablation of ACVR1B in the uterus using Pgr -Cre results in defects in female fertility and placental development [ 66 ].…”

The role of TGFβsuperfamily members in the pathophysiology of endometriosis

“…Importantly, alterations in their expression have been noted in disorders such as infertility, recurrent miscarriages, uterine-placental dysfunction, cervical cancer and endometriosis [7,33,47,48].…”