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Testicular macrophages are the principal immune cells in the testis. In addition to their classical immune roles, they regulate male hormone synthesis by Leydig cells, regeneration of Leydig cells, spermatogonia proliferation and differentiation, maintenance of testis-specific environment for sperm formation, and testis development. The juvenile and adult testes contain two distinct macrophage populations with unique tissue localization, genetic markers, morphology, and function. The interstitial macrophages are physically and functionally connected to Leydig cells, while the peritubular macrophages localize around the seminiferous tubules and are crucial for spermatogonia differentiation. Macrophages in the fetal testes regulate testis vasculature formation and clearance of mislocated cells. The origin of testicular macrophages is unclear. Some studies suggest their origin from the yolk sac and others from the bone marrow-derived monocytes. We discuss this issue at the end of this review article., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Macrophages are dynamic and plastic immune cells essential for tissue homeostasis and pathogen defense. Their cell cycle regulation is highly influenced by intrinsic and extrinsic signals facilitating rapid responses to infections and tissue damage. Dysregulation of their cell cycle leads to diseases like cancer and HIV. This chapter highlights aspects of the macrophage cell cycle crucial for the development of targeted therapies., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Epigenetic marks, such as DNA methylation and posttranslational modifications of core histones, are the key regulators of gene expression. In the mouse, many of these marks are erased during gamete formation and must be introduced de novo after fertilization. Some of them appear synchronously, but the others are deposited asynchronously and/or remain differently distributed on maternal and paternal chromatin. Although the mechanisms regulating these processes are not entirely understandable, it is commonly accepted that epigenetic reprogramming occurring during the first cell cycle of a mouse embryo is crucial for its further development. This chapter focuses on selected epigenetic modifications, such as DNA methylation, the introduction of histone variants, histones acetylation, phosphorylation, and methylation. Properly depositing these marks on maternal and paternal chromatin is crucial for normal embryonic development., (© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

The human intestinal tract is inhabited by trillions of microorganisms and houses the largest pool of macrophages in the human body. Being a part of the innate immune system, the macrophages, the professional phagocytes, vigorously respond to the microbial and dietary antigens present in the intestine. Because such a robust immune response poses the danger to the survival of the non-harmful and beneficial gut microbiota, the macrophages developed mechanisms of recognition and hyposensitivity toward the non-harmful/beneficial inhabitants of the gut. We will discuss the evolution and identity of some of these mechanisms in the following chapter.

In vertebrate cells, the Golgi apparatus is located in close proximity to the centriole. The architecture of the Golgi/centriole complex depends on a multitude of factors, including the actin filament cytoskeleton. In turn, both the Golgi and centriole act as the actin nucleation centers. Actin organization and polymerization also depend on the small GTPase RhoA pathway. In this chapter, we summarize the most current knowledge on how the genetic, magnetic, or pharmacologic interference with RhoA pathway and actin cytoskeleton directly or indirectly affects architecture, structure, and function of the Golgi/centriole complex.

Cdc6 is an important player in cell cycle regulation. It is involved in the regulation of both S-phase and M-phase. Its role during oogenesis is crucial for repression of the S-phase between the first and the second meiotic M-phases, and it also regulates, via CDK1 inhibition, the M-phase entry and exit. This is of special importance for the reactivation of the major M-phase-regulating kinase CDK1 (Cyclin-Dependent Kinase 1) in oocytes entering metaphase II of meiosis and in embryo cleavage divisions, in which precise timing allows coordination between cell cycle events and developmental program of the embryo. In this chapter, we discuss the role of Cdc6 protein in oocytes and early embryos.

In the majority of animals, the oocyte/egg is structurally, molecularly, and functionally asymmetric. Such asymmetry is a prerequisite for a flawless fertilization and faithful segregation of maternal determinants during subsequent embryonic development. The oocyte asymmetry develops during oogenesis and must be maintained during consecutive and obligatorily asymmetric oogonial divisions, which depending on the species lead to the formation of either oocyte alone or oocyte and nurse cell complex. In the following chapter, we summarize current knowledge on the asymmetric oogonial divisions in invertebrate (insects) and vertebrate (Xenopus) species.

Recent discoveries on the delivery of small- and large-size molecules and organelles to the oocytes/eggs from external sources, such as surrounding somatic cells, body fluids, and sperm, change our understanding of female germ cells' (oocytes and eggs) self-containment and individuality. In this chapter, we will summarize present-day knowledge on sources and presumptive functions of different types of exogenous molecules and organelles delivered to the animal oocytes and eggs.

RhoA is a small GTPase that, via its downstream effectors, regulates a variety of cell functions such as cytokinesis, cell migration, vesicular trafficking, and phagocytosis. As such the RhoA pathway is also pivotal for proper functioning of immune cells including macrophages. By controlling actin cytoskeleton organization, RhoA pathway modulates macrophage's polarity and basic functions: phagocytosis, migration, and extracellular matrix degradation. Numerous studies indicate that macrophages are very important effectors contributing to acute and chronic rejection of transplanted organs. In this review we discuss the role of RhoA pathway in governance of macrophage's functions in terms of transplanted organs.

Translationally Controlled Tumor-associated Protein (TCTP) is a small, 23 kDa multifunctional and ubiquitous protein localized both in the cytoplasm and in the nucleus of eukaryotic cells. It is evolutionarily highly conserved. Certain aspects of its structure show remarkable similarities to guanine nucleotide-free chaperons Mss4 and Dss4 suggesting that at least some functions of TCTP may depend on its chaperon-like action on other proteins. Besides other functions, TCTP is clearly involved in cell cycle regulation. It is also regulated in a cell-cycle-dependent manner suggesting a reciprocal interaction between this protein and the cell cycle-regulating machinery. TCTP also interacts with the cytoskeleton, mostly with actin microfilaments (MFs) and microtubules (MTs). It regulates the cytoskeleton organization and through this action it also influences cell shape and motility. The exact role of TCTP in cell cycle and cytoskeleton regulation is certainly not fully understood. In this chapter, we summarize recent data on cell cycle and cytoskeletal aspects of TCTP regulatory role.

The earliest manifestation of gonadogenesis in vertebrates is the formation of the genital ridges. The genital ridges form through the transformation of monolayer coelomic epithelium into a cluster of somatic cells. This process depends on increased proliferation of coelomic epithelium and disintegration of its basement membrane, which is foreshadowed by the expression of series of regulatory genes. The earliest expressed gene is Gata4, followed by Sf1, Lhx9, Emx2, and Cbx2. The early genital ridge is a mass of somatic SF1-positive cells (gonadal precursor cells) that derive from proliferating coelomic epithelium. Primordial germ cells (PGCs) immigrate to the coelomic epithelium even in the absence of genital ridges, e.g., in mouse null mutants for Gata4. And conversely, the PGCs are not required for the formation of the genital ridges. After reaching genital ridges, the PGCs become enclosed by somatic cells derived from coelomic epithelium. Subsequently, the expression of sex-determining genes begins and the bipotential gonads differentiate into either testes or ovaries. Gonadal precursor cells, derived from coelomic epithelium, give rise to the somatic supporting cells such as Sertoli cells, follicular cells, and probably also peritubular myoid and steroidogenic cells.

Oocyte maturation and early embryo development require precise coordination between cell cycle progression and the developmental programme. Cyclin B plays a major role in this process: its accumulation and degradation is critical for driving the cell cycle through activation and inactivation of the major cell cycle kinase, CDK1. CDK1 activation is required for M-phase entry whereas its inactivation leads to exit from M-phase. The tempo of oocyte meiotic and embryonic mitotic divisions is set by the rate of cyclin B accumulation and the timing of its destruction. By controlling when cyclin B destruction is triggered and by co-ordinating this with the completion of chromosome alignment, the spindle assembly checkpoint (SAC) is a critical quality control system important for averting aneuploidy and for building in the flexibility required to better integrate cell cycle progression with development. In this review we focus on cyclin B metabolism in mouse oocytes and embryos and illustrate how the cell cycle-powered clock (in fact cyclin B-powered clock) controls oocyte maturation and early embryo development, thereby providing important insight into human reproduction and potential causes of Down syndrome.

Cell polarity and asymmetry play a fundamental role in embryo development. The unequal segregation of determinants, cues, and activities is the major event in the differentiation of cell fate and function in all multicellular organisms. In oocytes, polarity and asymmetry in the distribution of different molecules are prerequisites for the progression and proper outcome of embryonic development. The mouse oocyte, like the oocytes of other mammals, seems to apply a less stringent strategy of polarization than other vertebrates. The mouse embryo undergoes a regulative type of development, which permits the full rectification of development even if the embryo loses up to half of its cells or its size is experimentally doubled during the early stages of embryogenesis. Such pliability is strongly related to the proper oocyte polarization before fertilization. Thus, the molecular mechanisms leading to the development and maintenance of oocyte polarity must be included in any fundamental understanding of the principles of embryo development. In this chapter, we provide an overview of current knowledge regarding the development and maintenance of polarity and asymmetry in the distribution of organelles and molecules in the mouse oocyte. Curiously, the mouse oocyte becomes polarized at least twice during ontogenesis; the question of how this phenomenon is achieved and what role it might play is addressed in this chapter.

The cell cycle consists of four main phases: G(1), S, G(2), and M. Most cells undergo these cycles up to 40-60 times in their life. However, neurons remain in a nondividing, nonreplicating phase, G(0). Neurons initiate but do not complete cell division, eventually entering apoptosis. Research has suggested that like cancer, Alzheimer's disease (AD) involves dysfunction in neuronal cell cycle reentry, leading to the development of the two-hit hypothesis of AD. The first hit is abnormal cell cycle reentry, which typically results in neuronal apoptosis and prevention of AD. However, with the second hit of chronic oxidative damage preventing apoptosis, neurons gain "immortality" analogous to tumor cells. Once both of these hits are activated, AD can develop and produce senile plaques and neurofibrillary tangles throughout brain tissue. In this review, we propose a mechanism for neuronal cell cycle reentry and the development of AD.

Our current understanding of the origin and evolution of the cell cycle is largely filled with gaps and unresolved questions. Numerous similarities between the processes comprising the cell cycle in distant organisms from the Pro- and Eukaryota kingdoms provide some clues about the course that evolution has taken. Contemporary Prokaryotes and Eukaryotes regulate their cell cycles in a quite similar way, using a master oscillator that regulates cell division. Despite this striking similarity, they use entirely different molecules for this purpose. The necessity to keep the master oscillator intact for the survival of every cell/organism allows evolutionary changes in only the secondary mechanisms and processes of the cell cycle. This is especially clear in oocytes and embryos, which have a direct impact on the reproductive success of an adult organism. Here, we present examples of cues driving such mild evolutionary changes of certain aspects of cell cycle progression in oocytes and early embryos. We suggest that weak linkages between core processes that rely on randomness (stochasticity) have led to the evolution of strategies increasing fitness similar to bet-hedging, a stochastic-based survival strategy of risk minimization widely implemented by populations of bacteria, yeast, arthropods, and birds. Stochastic diversification of phenotypes by isogenic cells increases their fitness in unpredictable environments and improves their survival rate upon exposure to stress, a trait beneficial in evading antibiotic treatment by bacteria or withstanding chemotherapy by cancer cells. The evolution of bet-hedging has been observed experimentally for bacteria and attributed to specific molecular mechanisms involved in this strategy. In this chapter, we set out to answer whether similar strategies could have evolved at the level of oocytes and embryos. We indicate possible evolutionary cues capable of realizing bet-hedging-like mechanisms.