*Review* **Molecular Signaling Regulating Endometrium–Blastocyst Crosstalk**

**Micol Massimiani 1,2 , Valentina Lacconi <sup>1</sup> , Fabio La Civita <sup>1</sup> , Carlo Ticconi <sup>3</sup> , Rocco Rago <sup>4</sup> and Luisa Campagnolo 1,\***


Received: 27 October 2019; Accepted: 16 December 2019; Published: 18 December 2019

**Abstract:** Implantation of the embryo into the uterine endometrium is one of the most finely-regulated processes that leads to the establishment of a successful pregnancy. A plethora of factors are released in a time-specific fashion to synchronize the differentiation program of both the embryo and the endometrium. Indeed, blastocyst implantation in the uterus occurs in a limited time frame called the "window of implantation" (WOI), during which the maternal endometrium undergoes dramatic changes, collectively called "decidualization". Decidualization is guided not just by maternal factors (e.g., estrogen, progesterone, thyroid hormone), but also by molecules secreted by the embryo, such as chorionic gonadotropin (CG) and interleukin-1β (IL-1 β), just to cite few. Once reached the uterine cavity, the embryo orients correctly toward the uterine epithelium, interacts with specialized structures, called pinopodes, and begins the process of adhesion and invasion. All these events are guided by factors secreted by both the endometrium and the embryo, such as leukemia inhibitory factor (LIF), integrins and their ligands, adhesion molecules, Notch family members, and metalloproteinases and their inhibitors. The aim of this review is to give an overview of the factors and mechanisms regulating implantation, with a focus on those involved in the complex crosstalk between the blastocyst and the endometrium.

**Keywords:** implantation; endometrium; blastocyst; embryo; chorionic gonadotropin; progesterone; Notch; cytokines
