Principles of Hand Fracture Management

The hand is essential in humans for physical manipulation of their surrounding environment. Allowing the ability to grasp, and differentiated from other animals by an opposing thumb, the main functions include both fine and gross motor skills as well as being a key tool for sensing and understanding the immediate surroundings of their owner

Inactivation of Retinoblastoma Protein (Rb1) in the Oocyte: Evidence That Dysregulated Follicle Growth Drives Ovarian Teratoma Formation in Mice

The origin of most ovarian tumors is undefined. Here, we report development of a novel mouse model in which conditional inactivation of the tumor suppressor gene Rb1 in oocytes leads to the formation of ovarian teratomas (OTs). While parthenogenetically activated ooctyes are a known source of OT in some mutant mouse models, enhanced parthenogenetic propensity in vitro was not observed for Rb1-deficient oocytes. Further analyses revealed that follicle recruitment and growth is disrupted in ovaries of mice with conditional inactivation of Rb1, leading to abnormal accumulation of secondary/preantral follicles. These findings underpin the concept that miscues between the germ cell and somatic compartments cause premature oocyte activation and the formation of OTs. Furthermore, these results suggest that defects in folliculogenesis and a permissive genetic background are sufficient to drive OT development, even in the absence of enhanced parthenogenetic activation. Thus, we have discovered a novel role of Rb1 in regulating the entry of primordial oocytes into the pool of growing follicles and signaling between the oocyte and granulosa cells during the protracted process of oocyte growth. Our findings, coupled with data from studies of other OT models, suggest that defects in the coordinated regulation between growth of the oocyte and somatic components in follicles are an underlying cause of OT formation

ZGLP1 is a determinant for the oogenic fate in mice

生殖細胞が卵母細胞へと分化する仕組みを解明. 京都大学プレスリリース. 2020-02-14.Mammalian sexual reproduction relies on the dichotomy of male and female germ cell development. However, the underlying mechanisms remain unclear. Here, we show that ZGLP1, a conserved transcriptional regulator with GATA-like zinc fingers, determines the oogenic fate in mice. ZGLP1 acts downstream of bone morphogenetic protein (BMP), but not retinoic acid (RA), and is essential for the oogenic program and meiotic entry. ZGLP1 overexpression induces differentiation of in vitro primordial germ cell-like cells (PGCLCs) into fetal oocytes by activating the oogenic programs repressed by Polycomb activities, whereas RA signaling contributes to the oogenic program maturation and PGC program repression. Our findings elucidate the mechanism for mammalian oogenic fate determination, providing a foundation for promoting in vitro gametogenesis and reproductive medicine

Evidence for paternal age-related alterations in meiotic chromosome dynamics in the mouse

Increasing age in a woman is a well-documented risk factor for meiotic errors, but the effect of paternal age is less clear. Although it is generally agreed that spermatogenesis declines with age, the mechanisms that account for this remain unclear. Because meiosis involves a complex and tightly regulated series of processes that include DNA replication, DNA repair, and cell cycle regulation, we postulated that the effects of age might be evident as an increase in the frequency of meiotic errors. Accordingly, we analyzed spermatogenesis in male mice of different ages, examining meiotic chromosome dynamics in spermatocytes at prophase, at metaphase I, and at metaphase II. Our analyses demonstrate that recombination levels are reduced in the first wave of spermatogenesis in juvenile mice but increase in older males. We also observed age-dependent increases in XY chromosome pairing failure at pachytene and in the frequency of prematurely separated autosomal homologs at metaphase I. However, we found no evidence of an age-related increase in aneuploidy at metaphase II, indicating that cells harboring meiotic errors are eliminated by cycle checkpoint mechanisms, regardless of paternal age. Taken together, our data suggest that advancing paternal age affects pairing, synapsis, and recombination between homologous chromosomes--and likely results in reduced sperm counts due to germ cell loss--but is not an important contributor to aneuploidy

Entwicklung eines Modells zur Berechnung und Kompensation thermo-elastischer Form- und Maßfehler bei der Trockenbearbeitung

<p>(A-C) Representative images of hematoxylin and eosin (H&E) stained cross-sections from ovaries of control mice (A), <i>Rb1-cKO</i> mice with classical teratoma (B), and <i>Rb1-cKO</i> mice with cystic teratoma (C). Scale bars = 100μm (A) and 500μm (B and C). (D) Representative images of H&E stained cross-sections from an ovary with classical teratoma displaying endoderm, ectoderm and mesoderm-derived tissues. Scale bar = 50μm. (E) Representative images of H&E stained cross-sections from an ovary with cystic teratoma. Scale bar = 50μm.</p

Propensity for parthenogenetic activation is not increased in <i>Rb1</i> deficient oocytes.

<p>(A) Representative bright field images of MII arrested oocytes from control and <i>Rb1-cKO</i> mice after 48 h of culture. Oocytes from control mice treated with 7% ethanol (EtOH) served as a positive control. (B) Quantitative comparison of the percent parthenogenetic activation (cleavage to 2-cell stage) after 48 h in culture for eggs from control and <i>Rb1-cKO</i> females. (C) Representative images of MII oocytes from control and <i>Rb1-cKO</i> mice immunostained for α-Tubulin and possessing a normal MII spindle (green) and chromosome alignment (blue). (D) Quantitative comparison of germinal vesicle (GV) stage oocytes recovered from control and <i>Rb1-cKO</i> mice 44–45 h after PMSG stimulation. (E and F) Quantitative comparison of the number of oocytes undergoing GV breakdown (GVBD) (E) and first polar body (PB) extrusion after 2–17 h in culture (F). Data represent mean±SEM for 3 mice of each genotype; *denotes significant difference at P<0.05.</p

Persistent Requirement and Alteration of the Key Targets of PRDM1 During Primordial Germ Cell Development in Mice

Primordial germ cells (PGCs) are the foundation of totipotency and vital for reproduction and heredity. PGCs in mice arise from the epiblast around Embryonic Day (E) 7.0, migrate through the hindgut endoderm, and colonize and proliferate in the embryonic gonads until around E13.5 prior to their differentiation either into prospermatogonia or oogonia. PRDM1, a transcriptional repressor, plays an essential role in PGC specification that includes robustly repressing a somatic mesodermal program. Using an inducible conditional knockout system, we show here that PRDM1 is critically required throughout PGC development. When Prdm1 was deleted in migrating PGCs at E9.5 or E10.5, or in male gonadal PGCs at E11.5, PGCs were eliminated by apoptosis from around E10.5, E11.5, or E13.5, respectively. When Prdm1 was deleted in female gonadal PGCs at E11.5, PGCs progressed into the first meiotic prophase in an apparently normal fashion, but the oogonia exhibited an aberrant pachytene phenotype, undergoing abrupt apoptosis from around E16.5. The escape of a fraction of PGCs (∼10%) from the Prdm1 deletion was sufficient to recover fairly normal germ cell pools, both in male and female adults. The key targets of PRDM1 in migrating and/or gonadal PGCs, including genes for development, apoptosis, and prospermatogonial differentiation, showed only a modest overlap with those upon PGC specification, and were enriched with histone H3 lysine 27 trimethylation (H3K27me3). Our findings provide critical insight into the mechanism for maintaining the transcriptional integrity of PGCs. </p