MicroRNAs and spermatogenesis Noora Kotaja, Ph.D.  Fertility and Sterility  Volume 101, Issue 6, Pages 1552-1562 (June 2014) DOI: 10.1016/j.fertnstert.2014.04.025 Copyright © 2014 American Society for Reproductive Medicine Terms and Conditions

Figure 1 Expression and function of microRNAs (miRNAs) during male germ cell differentiation in mice. Male germ cell differentiation starting from primordial germ cells (PGC) and ending with mature fertile spermatozoa is indicated on the left side of the figure. Germ cells initiate differentiation after birth by mitotic proliferation of spermatogonia (Sg). After entering to the meiotic pathway germ cells are called spermatocytes (Spc). Meiosis includes several phases (PL, preleptotene; L, leptotene; Z, zygotene; P, pachytene; D, diplotene). At the end of meiotic phase, two subsequent fast divisions (MI and MII) result in haploid round spermatids (RS) that undergo a dramatic cell differentiation. In elongating spermatids (ES), chromatin is tightly compacted by replacing somatic histones by protamines. Gene expression is active during spermatogenesis. Particularly, late Spcs and RSs are transcriptionally highly competent. Transcription ceases in ES due to chromatin compaction. The timing of the appearance of specific cell types during the first wave of spermatogenesis in juvenile mice is indicated as days postpartum (dpp). The figure lists some mouse miRNAs reported to be expressed preferentially or exclusively in a specific male germ cell type. Those miRNAs with experimentally demonstrated functions in mouse studies are indicated in bold. Their reported functions are in parenthesis. Some miRNAs with affected expression profiles in males with spermatogenic failure are listed in a separate box. This figure is not comprehensive but aims to give some examples of the spermatogenic miRNAs and their proposed functions. Fertility and Sterility 2014 101, 1552-1562DOI: (10.1016/j.fertnstert.2014.04.025) Copyright © 2014 American Society for Reproductive Medicine Terms and Conditions

Figure 2 Summary of the knockout mouse models to study the microRNA/small interfering RNA (miRNA/siRNA) pathways in male germ cells, and their spermatogenic phenotypes. The upper part of the figure demonstrates the timing of the Cre-mediated gene deletion in different germ cell-specific Dicer1 knockout (KO) mouse models discussed in this review. The most prominent spermatogenic defects are indicated for each conditional knockout model. The lower part of the figure shows the most affected phase of spermatogenesis in other knockout mouse models (Lin28 and Ago4 knockout) that affect miRNA pathways. PGC = primordial germ cell; Sg = spermatogonium; Spc = spermatocyte; RS = round spermatid; ES = elongating spermatid; MSCI = meiotic sex chromosome inactivation. Fertility and Sterility 2014 101, 1552-1562DOI: (10.1016/j.fertnstert.2014.04.025) Copyright © 2014 American Society for Reproductive Medicine Terms and Conditions