Publications by authors named "Hugh Clarke"

Article Synopsis
  • The study explores the role of glycerol-3-phosphate phosphatase (G3PP) in male fertility, highlighting its crucial expression in the testis and sperm, especially during spermatogenesis.
  • Researchers found that male mice lacking G3PP (cG3PP-KO) are infertile due to dysfunctional sperm with poor motility and increased oxidative stress, while a tamoxifen-inducible version (icG3PP-KO) maintained some fertility due to a small number of normal sperm.
  • The results suggest that G3PP is vital for sperm function and health, as its absence leads to abnormal sperm production and metabolism, impacting overall male fertility.
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Development of the mammalian oocyte requires physical contact with the surrounding granulosa cells of the follicle, which provide it with essential nutrients and regulatory signals. This contact is achieved through specialized filopodia, termed transzonal projections (TZPs), that extend from the granulosa cells to the oocyte surface. Transforming growth factor (TGFβ) family ligands produced by the oocyte increase the number of TZPs, but how they do so is unknown.

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The oocyte must grow and mature before fertilization, thanks to a close dialogue with the somatic cells that surround it. Part of this communication is through filopodia-like protrusions, called transzonal projections (TZPs), sent by the somatic cells to the oocyte membrane. To investigate the contribution of TZPs to oocyte quality, we impaired their structure by generating a full knockout mouse of the TZP structural component myosin-X (MYO10).

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The development of germ cells relies on contact and communication with neighboring somatic cells that provide metabolic support and regulatory signals. In females, contact is achieved through thin cytoplasmic processes that project from follicle cells surrounding the oocyte, extend through an extracellular matrix (ECM) that lies between them, and reach its surface. In mammals, the ECM is termed the zona pellucida and the follicular cell processes are termed transzonal projections (TZPs).

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Objective: Auditory enhancements to the pulse oximetry tone may help clinicians detect deviations from target ranges for oxygen saturation (SpO) and heart rate (HR).

Background: Clinical guidelines recommend target ranges for SpO and HR during neonatal resuscitation in the first 10 minutes after birth. The pulse oximeter currently maps HR to tone rate, and SpO to tone pitch.

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Granulosa cells of growing ovarian follicles elaborate filopodia-like structures termed transzonal projections (TZPs) that supply the enclosed oocyte with factors essential for its development. Little is known, however, of the mechanisms underlying the generation of TZPs. We show in mouse and human that filopodia, defined by an actin backbone, emerge from granulosa cells in early stage primary follicles and that actin-rich TZPs become detectable as soon as a space corresponding to the zona pellucida appears.

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In many non-mammalian organisms, a population of germ-line stem cells supports continuing production of gametes during post-natal life, and germ-line stem cells are also present and functional in male mammals. Traditionally, however, they have been thought not to exist in female mammals, who instead generate all their germ cells during fetal life. Over the last several years, this dogma has been challenged by several reports, while being supported by others.

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Germ cells are physically coupled to somatic support cells of the gonad during differentiation, but this coupling must be disrupted when they are mature, freeing them to participate in fertilization. In mammalian females, coupling occurs via specialized filopodia that project from the ovarian follicular granulosa cells to the oocyte. Here, we show that signaling through the epidermal growth factor receptor (EGFR) in the granulosa, which becomes activated at ovulation, uncouples the germ and somatic cells by triggering a massive and temporally synchronized retraction of the filopodia.

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Ovarian follicle development is regulated by locally produced TGFβ superfamily members. The TGFβ type III receptor (TGFBR3, or betaglycan), which regulates the actions of diverse TGFβ ligands, including inhibins, is expressed in different ovarian cell types. However, its functional roles in the ovary have not been investigated in vivo.

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Development and differentiation of a functional oocyte that following fertilization is able to give rise to a new individual requires continuous physical contact with the supporting somatic cells of the ovarian follicle. As the oocyte is surrounded by a thick extracellular coat, termed the , this essential contact is mediated through thin cytoplasmic filaments known as transzonal projections (TZPs) that project from the somatic granulosa cells adjacent to the oocyte and penetrate through the to reach the oocyte. Gap junctions assembled where the tips of the TZPs contact the oocyte plasma membrane, and other contact-dependent signaling may also occur at these sites.

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Analysis of the mechanisms that drive the growth and meiotic maturation of the female germ cell, the oocyte, has been greatly facilitated by the development of conditions that support these processes in vitro. Easily identified signposts of oocyte differentiation enable the ability of specific culture conditions to recapitulate normal oocyte development to be robustly assayed. Here we describe a technique for deriving complexes consisting of an oocyte surrounded by somatic granulosa cells from follicles and growing these granulosa cell-oocyte complexes in vitro.

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In many cell types, the length of the poly(A) tail of an mRNA is closely linked to its fate - a long tail is associated with active translation, a short tail with silencing and degradation. During mammalian oocyte development, two contrasting patterns of polyadenylation have been identified. Some mRNAs carry a long poly(A) tail during the growth stage and are actively translated, then become deadenylated and down-regulated during the subsequent stage, termed meiotic maturation.

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Germ cells develop in a microenvironment created by the somatic cells of the gonad [1-3]. Although in males, the germ and somatic support cells lie in direct contact, in females, a thick extracellular coat surrounds the oocyte, physically separating it from the somatic follicle cells [4]. To bypass this barrier to communication, narrow cytoplasmic extensions of the follicle cells traverse the extracellular coat to reach the oocyte plasma membrane [5-9].

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The article https://doi.org/10.1093/biolre/iox090 has been withdrawn because it is a duplicate of https://doi.

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Prior to ovulation, the mammalian oocyte undergoes a process of differentiation within the ovarian follicle that confers on it the ability to give rise to an embryo. Differentiation comprises two phases-growth, during which the oocyte increases more than 100-fold in volume as it accumulates macromolecules and organelles that will sustain early embryogenesis; and meiotic maturation, during which the oocyte executes the first meiotic division and prepares for the second division. Entry of an oocyte into the growth phase appears to be triggered when the adjacent granulosa cells produce specific growth factors.

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Development of animal germ cells depends critically on continuous contact and communication with the somatic compartment of the gonad. In females, each oocyte is enclosed within a follicle, whose somatic cells supply nutrients that sustain basal metabolic activity of the oocyte and send signals that regulate its differentiation. This maternal microenvironment thus plays an indispensable role in ensuring the production of fully differentiated oocytes that can give rise to healthy embryos.

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In the mammalian ovary, each oocyte grows and develops within its own structural and developmental niche-the follicle. Together with the female germ cell in the follicle are somatic granulosa cells, specialized companion cells that surround the oocyte and provide support to it, and an outer layer of thecal cells that serve crucial roles including steroid synthesis. These follicular compartments function as a single physiological unit whose purpose is to produce a healthy egg, which upon ovulation can be fertilized and give rise to a healthy embryo, thus enabling the female germ cell to fulfill its reproductive potential.

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Reproduction depends on the generation of healthy oocytes. Improving therapeutic strategies to prolong or rescue fertility depends on identifying the inter- and intracellular mechanisms that direct oocyte development under physiological conditions. Growth and proliferation of multiple cell types is regulated by the Hippo signaling pathway, whose chief effectors are the transcriptional co-activator YAP and its paralogue WWTR1.

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Although genetic mutations have long been known to influence gene expression and individual phenotype, studies emerging over the past decade indicate that such changes can also be induced in the absence of alterations in base-sequence. Epigenetically driven changes in gene expression or phenotype, when they are transmitted to succeeding generations, represent an entirely new mechanism that could generate heritable variation in a population. To understand the mechanistic basis of epigenetic inheritance, it is essential to learn how these changes may be transmitted through the germ-line to the next generation.

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