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The Regulators of Mouse Spermatogenic Cell Fate Decisions
Biochemistry and Molecular Biology
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Spermatogenesis is the process of maturation of a male germ cell from a spermatogonium to a spermatozoon. During this developmental process, spermatogonia, on one hand, replicate themselves as a replacement of germ cell stem cells and on the other hand differentiate into spermatocytes, which undergo meiosis and give rise to haploid spermatids. The haploid spermatids then go through a series of transformation termed spermiogenesis to generate mature spermatozoa. Many regulators are involved in this complicated process to ensure sperm formation proceeds smoothly. Each step in spermatogenesis needs specific genes for newly appearing functional proteins as well as specific regulators to modulate expression of those genes. Among these regulators, we found that microRNAs play a significant role in controlling the fate of mRNAs during spermatogenesis. Our data showed that there is a particular pattern of gene expression during spermatogenesis in which some genes display a ‘delayed translation' due to the cessation of transcription in elongating/elongated spermatids. In this study we hypothesized that microRNAs participate in controlling the distribution and movement of those ‘translationally delayed' mRNAs between ribonucleoprotein particles (RNPs), which are considered to be a storage compartment for mRNAs, and cytoplasmic polysomes that are located at sites of translation. Besides noncoding RNAs, many protein factors are also involved in the spermatogenic cell fate control process, including RNA-binding proteins, ubiquitination proteins, autophagy proteins, etc. We evaluated the function of the ubiquitination-related protein BAT3 during spermatogenesis and found that the protein is involved in autophagy by interacting with autophagy proteins, including ATG5, ATG7, and LG3. Without BAT3, spermatogenesis cannot be completed, and no mature spermatozoa are produced causing male infertility. In these studies, we primarily focused on the regulatory functions of microRNAs and BAT3 in the control the normal development of spermatogenic cells and normal male fertility.