**Asghar Ali \* , Gerrit J. Bouma, Russell V. Anthony and Quinton A. Winger**

Department of Biomedical Sciences, Animal Reproduction and Biotechnology Laboratory, 1683 Campus Delivery, Colorado State University, Fort Collins, CO 80523, USA; gerrit.bouma@colostate.edu (G.J.B.); russ.anthony@colostate.edu (R.V.A.); quinton.winger@colostate.edu (Q.A.W.)

**\*** Correspondence: asghar.ali@colostate.edu

Received: 17 April 2020; Accepted: 18 May 2020; Published: 21 May 2020

**Abstract:** Placental disorders are a major cause of pregnancy loss in humans, and 40–60% of embryos are lost between fertilization and birth. Successful embryo implantation and placental development requires rapid proliferation, invasion, and migration of trophoblast cells. In recent years, microRNAs (miRNAs) have emerged as key regulators of molecular pathways involved in trophoblast function. A miRNA binds its target mRNA in the 30 -untranslated region (30 -UTR), causing its degradation or translational repression. Lethal-7 (*let-7*) miRNAs induce cell differentiation and reduce cell proliferation by targeting proliferation-associated genes. The oncoprotein LIN28 represses the biogenesis of mature *let-7* miRNAs. Proliferating cells have high LIN28 and low *let-7* miRNAs, whereas differentiating cells have low LIN28 and high *let-7* miRNAs. In placenta, low LIN28 and high *let-7* miRNAs can lead to reduced proliferation of trophoblast cells, resulting in abnormal placental development. In trophoblast cells, *let-7* miRNAs reduce the expression of proliferation factors either directly by binding their mRNA in 30 -UTR or indirectly by targeting the AT-rich interaction domain (ARID)3B complex, a transcription-activating complex comprised of ARID3A, ARID3B, and histone demethylase 4C (KDM4C). In this review, we discuss regulation of trophoblast function by miRNAs, focusing on the role of LIN28-*let-7*-ARID3B pathway in placental development.

**Keywords:** miRNA; trophoblast cells; cell proliferation; ARID3B complex
