Citation: Hoshino, Y.; Uchida, T. Prolyl isomerase, Pin1, Controls Meiotic Progression in Mouse Oocytes. Cells 2022, 11, 3772. https://doi.org/10.3390/ cells11233772 Academic Editors: Silvia Garagna and Giovanni Levi Received: 14 October 2022 Accepted: 24 November 2022 Published: 25 November 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). cells Article Prolyl Isomerase, Pin1, Controls Meiotic Progression in Mouse Oocytes Yumi Hoshino 1,2, * and Takafumi Uchida 3 1 Laboratory of Animal Reproduction, Graduate School of Integrated Science for Life, Hiroshima University, Hiroshima 739-8528, Japan 2 Laboratory of Reproductive Biology, Faculty of Science, Japan Women’s University, Tokyo 112-8681, Japan 3 Laboratory of Molecular Enzymology, Department of Molecular Cell Science, Graduate School of Agricultural Science, Tohoku University, Miyagi 981-8555, Japan * Correspondence: yumihoshino.yh@gmail.com Abstract: During meiotic maturation, accurate progression of meiosis is ensured by multiple protein kinases and by signal transduction pathways they are involved in. However, the mechanisms regulating the functions of phosphorylated proteins are unclear. Herein, we investigated the role of Pin1, a peptidyl-prolyl cis-trans isomerase family member that regulates protein functions by altering the structure of the peptide bond of proline in phosphorylated proteins in meiosis. First, we analyzed changes in the expression of Pin1 during meiotic maturation and found that although its levels were constant, its localization was dynamic in different stages of meiosis. Furthermore, we confirmed that the spindle rotates near the cortex when Pin1 is inhibited by juglone during meiotic maturation, resulting in an error in the extrusion of the first polar body. In Pin1 −/− mice, frequent polar body extrusion errors were observed in ovulation, providing insights into the mechanism underlying the errors in the extrusion of the polar body. Although multiple factors and mechanisms might be involved, Pin1 functions in meiosis progression via actin- and microtubule-associated phosphorylated protein targets. Our results show that functional regulation of Pin1 is indispensable in oocyte production and should be considered while developing oocyte culture technologies for reproductive medicine and animal breeding. Keywords: oocyte; meiotic maturation; Pin1; phosphorylation; mouse 1. Introduction The resumption of meiosis after diplotene arrest, progression through metaphase I (MI), and re-arrest at metaphase II (MII) are essential for meiotic maturation in mammalian oocytes. These processes are controlled by cyclic changes in the activity of cyclin-dependent kinase 1 as well as by cyclin B1 degradation, which lead to stabilization/destabilization of the maturation-promoting factor [1,2]. Oocytes acquire fertilization and developmental competence by synchronizing nuclear and cytoplasmic maturation during meiosis. Nuclear maturation involves germinal vesicle (GV) breakdown (GVBD) and assembly of the meiosis I spindle. Eccentric positioning of the spindle leads to asymmetric cell division, which coincides with a reduction in the number of chromosomes through the extrusion of the first polar body and maximal retention of the cytoplasm of oocytes [3]. These events occurring during oocyte maturation are regulated by multiple kinases [4–6], particularly serine or threonine (Ser/Thr) protein kinases [7]. Moreover, when oocytes are exposed to intracellular signals after stimulation with endogenous luteinizing hormone, meiosis resumes selectively and stops again at MII to maintain the fertilization ability. In a previous study, we reported the role of Akt (protein kinase B), a Ser/Thr protein kinase, in the formation of the meiotic spindle and the extrusion of the second polar body in mouse oocytes [6]. Additionally, another Ser/Thr kinase, the mammalian target of rapamycin (mTOR), forms a complex with raptor or rictor—the mTOR/raptor complex Cells 2022, 11, 3772. https://doi.org/10.3390/cells11233772 https://www.mdpi.com/journal/cells