Journal of Reproduction and Development
Online ISSN : 1348-4400
Print ISSN : 0916-8818
ISSN-L : 0916-8818
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  • 67 巻 (2021) 6 号 p. 386-391
    Steroidal but not embryonic regulation of mucin 1 expression in bovine endometrium もっと読む
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    Cover Story:
    The endometrial surface is required to reject attachment of exogenous undesirable substances such as pathogens, while occasionally shifting properties to allow physical interaction with an embryo to support a successful pregnancy. Kubota et al. reported that MUC1, a potent inhibitor of cellular contact via its large extracellular glycoprotein domain, localizes to the apical surface of bovine endometrium (upper panel, green staining). This MUC1 barrier can be removed in response to steroid signaling at receptive phase and during pregnancy (lower panel), as revealed by immunohistochemistry (p. 386–391). Red signal (pseudo-color) represents DAPI-stained nuclei. Interestingly, MUC1 expression is elevated in the endometrium of cows with a long postpartum interval, which is a known risk for reducing female fertility. Thus, this observation is consistent with the proposed anti-attachment role of MUC1. These results suggest that MUC1 regulation plays a role in endometrial homeostasis and embryo implantation, and its negative correlation with fertility may be used as a diagnostic of reproductive efficiency.

  • 67 巻 (2021) 5 号 p. 300-306
    Reestablishment of transzonal projections and growth of bovine oocytes in vitro もっと読む
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    Cover Story:
    Bidirectional communication between oocytes and granulosa cells or cumulus cells is maintained through transzonal projections (TZPs). These structures are important for oocyte growth, although the mechanism underlying TZP development remains unclear. Fushii et al. demonstrated the disappearance of TZPs by denudation of bovine growing oocytes and the reestablishment of TZPs by coculture of TZP-free denuded oocytes (DOs) with mural granulosa cells (MGCs) (Fushii et al. pp. 300–306). Twenty-four hours after denudation, almost all TZPs disappeared, and after coculture and subsequent growth culture of DOs with MGCs, TZPs were reestablished (upper). Additionally, the oocytes in reconstructed complexes grew fully and acquired meiotic competence, suggesting that the reestablished TZPs are able to support oocyte growth similar to those in cultured oocyte-cumulus cell-mural granulosa cell complexes (middle) and in vivo grown oocytes (lower).

  • 67 巻 (2021) 4 号 p. 273-281
    Effects of oocyte-derived growth factors on the growth of porcine oocytes and oocyte–cumulus cell complexes in vitro もっと読む
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    During oocyte growth and follicle development, oocytes closely communicate with cumulus cells. Morikawa et al. examined the effects of oocyte-derived growth factors, growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15), on the growth and acquisition of meiotic competence of porcine oocytes (Morikawa et al. pp. 273–281). Oocyte-cumulus cell complexes (OCCs) collected from early antral follicles were cultured in growth medium supplemented with GDF9 (upper left) and BMP15 (upper right) for 5 days. Only GDF9 increased the OCC diameter in a dose-dependent manner. OCCs that had been cultured with GDF9 or BMP15 were subjected to a subsequent maturation culture. Those OCCs cultured with GDF9 expanded loosely (lower left), whereas those with BMP15 expanded fully and matured to the second metaphase (lower right).

  • 67 巻 (2021) 3 号 p. 189-195
    Regulation of primordial follicle formation, dormancy, and activation in mice もっと読む
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    Cover Story:
    In mammalian female reproduction, primordial follicles serve as stores to sustain the ovulation cycle. Regulations of primordial follicle development, activation, and dormancy in mice are summarized in a review by Nagamatsu (pp. 189–195). The importance of mechanical stress, especially extracellular matrix (ECM)-mediated pressure, for the maintenance of primordial follicle dormancy was recently demonstrated. Primordial follicles treated with collagenase, trypsin, and knockout serum replacement (KSR) (this mixture called CTK) to digest ECM were examined by immunohistochemistry. Ovaries treated solely with phosphate-buffered saline displayed primordial follicles composed of flat granulosa cells and complex stress fibers, as revealed by phalloidin. In contrast, CTK treatment resulted in fewer stress fibers and cuboidal-shaped granulosa cells, suggesting oocyte activation.

  • 67 巻 (2021) 2 号 p. 79-81
    Lipid droplets are formed in 2-cell-like cells もっと読む
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    Cover Story:
    Recent studies suggested that a small sub-population of embryonic stem (ES) cells exhibit 2-cell stage embryo-like (2-cell-like) features, including the reactivation of murine endogenous retrovirus with leucin transfer RNA primer, high histone mobility, and dispersed chromocenters. Furuta et al. investigated the organelle morphology of 2-cell-like cells using electron microscopy (Furuta et al. Lipid droplets are formed in 2-cell-like cells. pp. 79–81). They demonstrated the formation of a lipid droplet during the transition from ES cells to 2-cell-like cells, and proposed that these cells utilize a unique energy storage and production pathway.

  • 67 巻 (2021) 1 号 p. 59-66
    Expression and localization of alpha-tubulin N-acetyltransferase 1 in the reproductive system of male mice もっと読む
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    Cover Story:
    Previous reports suggested the involvement of alpha-tubulin N-acetyltransferase 1 (ATAT1) in flagella formation in spermatozoa; however, whether ATAT1 is expressed in flagella and involved in spermatozoa maturation and capacitation remains to be elucidated. Yanai et al. evaluated the expression of ATAT1 in the male reproductive system in mice using immunostaining and western blotting (Yanai et al. Expression and localization of alpha-tubulin N-acetyltransferase 1 in the reproductive system of male mice. pp. 59–66). The localization of ATAT1 protein in the male germline was detected during spermiogenesis as well as spermatozoa maturation. Therefore, these results suggest that ATAT1 might be involved not only in flagella formation, but also in the acetylation process during spermatozoa maturation and capacitation.

  • 66 巻 (2020) 6 号 p. 515-522
    Expression and functions of cluster of differentiation 9 and 81 in rat mammary epithelial cells もっと読む
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    Cover Story: Cluster of differentiation 9 (CD9) forms a complex with CD81, and is a member of the tetraspanin superfamily. Cd9 and Cd81 are highly expressed in breast cancer cells, but their expression in healthy mammary glands remains unclear. Horiguchi et al. reported expression of Cd9 and Cd81 in mammary epithelial cells, with expression levels correlating with mammary gland development (Horiguchi et al. Expression and functions of cluster of differentiation 9 and 81 in rat mammary epithelial cells, pp. 515–522). To examine the functional roles of CD9 and CD81, Horiguchi et al. knocked down Cd9 and Cd81 gene expression using small interfering RNAs (siRNAs) in isolated CD9-positive mammary epithelial cells. They found that siRNAs against Cd9 and Cd81 inhibited estrogen-induced mammary epithelial cell proliferation. These findings provide novel insights into mammary epithelial cell proliferation during pregnancy and lactation, as well as in pathological processes associated with breast cancer.

  • 66 巻 (2020) 5 号 p. 411-419
    H4K20 monomethylation inhibition causes loss of genomic integrity in mouse preimplantation embryos もっと読む
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    Cover Story: 
    Loss of genomic integrity in preimplantation embryos can cause not only developmental arrest but also diseases such as congenital disorders and cancers. However, the key factors for maintaining genomic integrity in preimplantation embryos remain unknown. Shikata et al. reported that SETD8-mediated monomethylation of H4K20, a type of epigenetic modification, plays an important role in the maintenance of genomic integrity (Shikata et al. H4K20 monomethylation inhibition causes loss of genomic integrity in mouse preimplantation embryos. pp. 411–419). In our study, the inhibition of SETD8 or the overexpression of dominant-negative histone H4 mutants resulted in developmental arrest and excessive accumulation of DNA double-strand breaks, suggesting that H4K20 monomethylation is associated with DNA damage repair and is essential for preimplantation development.

  • 66 巻 (2020) 4 号 p. 341-349
    CD2 is a surface marker for mouse and rat spermatogonial stem cells もっと読む
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    Cover Story:
    Spermatogonial stem cells (SSCs) comprise merely a small population in the testis. To facilitate studies on SSCs, it is necessary to find markers that are expressed thereon. Kanatsu-Shinohara et al. discovered a new surface marker on mouse and rat SSCs  known as cluster of differentiation 2 (CD2) while studying the molecular mechanism of SSC aging (Kanatsu-Shinohara et al. CD2 is a surface marker for mouse and rat spermatogonial stem cells. pp. 341–349). Using a fluorescence-activated cell sorter, SSCs were enriched by 291.9-fold compared to those in wild-type mouse testes, based on CD2 expression. CD2 depletion by short hairpin RNA in cultured SSCs compromised their stem cell activity. Conserved CD2 expression on mouse and rat SSCs suggest that CD2 may also be expressed on SSCs from other animal species, including humans.

  • 66 巻 (2020) 3 号 p. 277-280
    An investigation of the time period within which frozen-thawed semen delivers a high conception rate in lactating dairy cows もっと読む
  • 66 巻 (2020) 2 号 p. 105-113
    Increased supply from blood vessels promotes the activation of dormant primordial follicles in mouse ovaries もっと読む
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    Cover Story:
    Most primordial follicles present in ovaries are dormant and only a few of them are activated in every estrus cycle. However, the mechanism controlling the activation of dormant primordial follicles in vivo remains unclear. In this study, Komatsu et al. found that almost all the activated primordial follicles (black arrows) made contact with blood vessels (red arrows) in mouse ovaries (Komatsu et al. Increased supply from blood vessels promotes the activation of dormant primordial follicles in mouse ovaries. pp. 105–113). To confirm the hypothesis that angiogenesis is crucial for activation of the dormant primordial follicles in vivo, Komatsu et al. induced angiogenesis using recombinant VEGF. They found that the activation of dormant primordial follicles was promoted by an increase in the number of blood vessels in the ovaries. Furthermore, the number of activated follicles increased in cultured ovarian tissues depending on the serum concentration in the medium. These results confirm that the supply of serum components through new blood vessels formed via angiogenesis is a cue for the activation of dormant primordial follicles in the ovaries.

  • 66 巻 (2020) 1 号 p. 67-73
    Production of mouse offspring from inactivated spermatozoa using horse PLCζ mRNA もっと読む
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    Cover Story:
    Improving artificial oocyte activation is essential for animal biotechnology, to obtain healthy offspring with a high success rate. Yamamoto et al. investigated whether the equine sperm-specific phospholipase C zeta (ePLCζ) mRNA, which has the strongest oocyte activation potential in mammals, could improve the mouse oocyte activation rate and subsequent embryonic development using inactivated spermatozoa (Yamamoto et al. Production of mouse offspring from inactivated spermatozoa using horse PLCζ mRNA. pp. 67–73). The activation potential of ePLCζ was ten times greater than that of murine (m) PLCζ and normal blastocysts were obtained. However, the birth rate was slightly, but significantly, decreased in oocytes activated by ePLCζ compared to those activated by mPLCζ. These results suggest that activation rate does not always correlate birth rate.

  • 65 巻 (2019) 6 号 p. 485-489
    Functional consequences of mitochondrial mismatch in reconstituted embryos and offspring もっと読む
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    Cover Story:
    The oocyte is the only cell that can reprogram a somatic nucleus to totipotency. The process of reprogramming is, however, only partially understood, and is accompanied by both epigenetic and structural changes in the somatic nucleus. The oocyte components that are necessary for a successful reprogramming and remodeling are unknown. In this issue, Fulka H et al. demonstrate that rather than the insoluble nuclear envelope, together with chromatin-bound factors, or the cytoplasm alone, it is the soluble nuclear fraction that has a major effect upon the somatic nucleus (Fulka H, et al.: Dissecting the role of the germinal vesicle nuclear envelope and soluble content in the process of somatic cell remodeling and reprogramming. pp. 433-441). This fraction is essential for altering the size of the somatic nucleus as well as transcriptional silencing and efficient histone H3.3 incorporation.

  • 65 巻 (2019) 5 号 p. 433-441
    Dissecting the role of the germinal vesicle nuclear envelope and soluble content in the process of somatic cell remodelling and reprogramming もっと読む
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    Cover Story:
    The oocyte is the only cell that can reprogram a somatic nucleus to totipotency. The process of reprogramming is, however, only partially understood, and is accompanied by both epigenetic and structural changes in the somatic nucleus. The oocyte components that are necessary for a successful reprogramming and remodeling are unknown. In this issue, Fulka H et al. demonstrate that rather than the insoluble nuclear envelope, together with chromatin-bound factors, or the cytoplasm alone, it is the soluble nuclear fraction that has a major effect upon the somatic nucleus (Fulka H, et al.: Dissecting the role of the germinal vesicle nuclear envelope and soluble content in the process of somatic cell remodeling and reprogramming. pp. 433-441). This fraction is essential for altering the size of the somatic nucleus as well as transcriptional silencing and efficient histone H3.3 incorporation.

  • 65 巻 (2019) 4 号 p. 281-287
    A way for in vitro/ex vivo egg production in mammals もっと読む
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    Cover Story:
    In vitro/ex vivo egg production has been widely studied in various mammalian species over half of the century to utilize the majority of the immature oocytes stocked in the female ovaries. Recently, the first successful protocol of in vitro oogenesis from primordial germ cells (PGC) has been established by Morohaku K, et al., resulting in the live birth of offspring in mice. The protocol consists of two vital steps; 1) ex vivo organ culture of mouse PGC ovaries to complete the process of follicle formation, with successful incorporation of antagonists for the existing estrogen receptors, and 2) in vitro follicle culture of the growing follicles isolated from the cultured ovaries. The review in this issue introduces the current findings and aspects governing in vitro oogenesis, with a brief history (Morohaku K. A way for in vitro/ex vivo egg production in mammals. pp. 281–287).

  • 65 巻 (2019) 3 号 p. 195-201
    Acquisition of developmental competence and in vitro growth culture of bovine oocytes もっと読む
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    Cover Story:
    In cattle, small oocytes (group VII), included in small follicles, grow with follicular development, and the size and developmental competence of oocytes increase (groups I and II) (Nagano, Acquisition of developmental competence and in vitro growth culture of bovine oocytes, pp. 195-201).  Subsequently, only one follicle is selected to develop to a dominant follicle and ovulates, but the other follicles start to degenerate. During the degeneration process, an accumulation of lipid droplets and undulation of the nuclear membrane of germinal vesicle start, and the developmental competence of oocytes also increases (pseudomaturation-like change in group III). However, too many pseudomaturation-like changes impair the developmental competence of oocytes (groups V and VI).  If oocytes start to degenerate before pseudomaturation-like changes, the oocytes may become group IV.

  • 65 巻 (2019) 2 号 p. 155-162
    Glycerol kinase 2 is essential for proper arrangement of crescent-like mitochondria to form the mitochondrial sheath during mouse spermatogenesis もっと読む
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    Cover Story:
    The mitochondrial sheath is composed of mitochondria that coil tightly around the midpiece of the sperm flagellum. Mitochondria are recruited from the cytoplasm to the flagellum late in spermatogenesis. Recruited mitochondria are initially spherical, but then elongate laterally to become crescent-like in shape. Subsequently, these crescent-like mitochondria elongate continuously to coil tightly around the flagellum. Mitochondrial sheath development in glycerol kinase 2 (Gk2)-disrupted mice, which show abnormal mitochondrial sheath formation, was observed using freeze-fracturing coupled with scanning electron microscopy (Shimada et al., Glycerol kinase 2 is essential for proper arrangement of crescent-like mitochondria to form the mitochondrial sheath during mouse spermatogenesis, pp. 155–162). Gk2-disrupted spermatids show abnormal localization of crescent-like mitochondria, despite initially exhibiting proper alignment of spherical mitochondria around the flagellum. These results indicate that GK2 is essential for proper arrangement of crescent-like mitochondria during mitochondrial sheath formation in mouse spermatogenesis.

  • 65 巻 (2019) 1 号 p. 57-66
    Destabilization of spindle assembly checkpoint causes aneuploidy during meiosis II in murine post-ovulatory aged oocytes もっと読む
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    Cover Story:
    Mammalian oocyte quality degrades over time after in vitro ovulation. As various oocyte manipulations employed in assisted reproductive technology are time consuming, post-ovulatory aging is a serious problem in reproductive medicine and ova research. Shimoi et al. investigated the effects of post-ovulatory aging on the incidence of chromosomal aneuploidy during meiosis II (MII), with a focus on the expression of functional proteins from the spindle assembly checkpoint (SAC) (Shimoi G et al.: Destabilization of spindle assembly checkpoint causes aneuploidy during meiosis II in murine post-ovulatory aged oocytes. pp. 57–66). This study showed that post-ovulatory oocyte aging inhibits MAD2 localization to the sister kinetochore. Furthermore, oocyte aging prevented cohesin subunits from being appropriately maintained or degraded. These results suggest that destabilization of SAC signaling causes sister chromatid segregation errors in MII oocytes and consequently increases the incidence of aneuploidy in early embryos.

  • 64 巻 (2018) 6 号 p. 469-476
    The roles of kisspeptin in the mechanism underlying reproductive functions in mammals もっと読む
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    Cover Story:
    The review article by Uenoyama et al. describes the roles of hypothalamic kisspeptin in the central mechanism regulating puberty and subsequent reproductive functions in mammals. The schematic illustration shows a possible mechanism regulating the pubertal augmentation of Kiss1 expression in the arcuate nucleus (ARC) to trigger pulsatile GnRH/gonadotropin secretion in rodents. The authors suspect that estrogen strongly suppresses ARC Kiss1 expression during the prepubertal period via direct and indirect pathways and that the sensitivity to estrogen negative feedback action on ARC Kiss1 expression decreases during the pubertal transition. The resultant increase in secretion of kisspeptin would trigger GnRH/gonadotropin secretion at pubertal onset (Uenoyama et al. The role of kisspeptin in the mechanism underlying reproductive function in mammals. pp. 469–476).

  • 64 巻 (2018) 5 号 p. 393-400
    DNA fragmentation in epididymal freeze-dried ram spermatozoa impairs embryo development もっと読む
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    Cover Story:
    Dry biobanking has many advantages over the current paradigm of storing cryopreserved cells under liquid nitrogen. During drying, however, the cells become damaged. The highly condensed spermatozoa DNA has been shown in many desiccation studies to generally maintain its integrity. Using ram freeze-dried epididymal spermatozoa as a model, Palazzese et al. were the first to evaluate both single- and double-strand DNA breaks (SSBs and DSBs, respectively), showing that drying causes minimal DSBs but extensive SSBs (Palazzese L et al., 2018. DNA fragmentation in epididymal freeze-dried ram spermatozoa impairs embryo development, pp. 393–400). Furthermore, the authors also demonstrated that spermatozoa capable of directing embryo development to the blastocyst stage in vitro originated from rams with the least DNA damage Overall, the impact of sperm DNA damage on embryonic development depends on a balance between the extent of sperm DNA fragmentation, fragmentation type, and the oocyte’s repair capacity.

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