In last few hours of maturation, the mouse oocyte takes up over twenty billion zinc atoms and arrests after first meiotic division, until fertilization or pharmacological intervention stimulates cell cycle progression toward a new embryo. Using chemical physical probes, we show that mature, zinc-enriched egg triggers ejection into extracellular milieu in series coordinated events termed sparks. These immediately follow well-established calcium oscillations within activated are evolutionarily...

Precise coordination of meiotic progression is a critical determinant an egg's capacity to be fertilized successfully, and zinc has emerged as key regulatory element in this process. An early manifestation role for transition metal the significant increase total intracellular zinc. This accumulation essential beyond telophase I establishment arrest at metaphase II. The subsequent developmental event, fertilization, induces rapid expulsion labile that hallmark event resumption. In present...

Development of uterine endometrial receptivity for implantation is orchestrated by cyclic steroid hormone-mediated signals. It unknown if these signals are necessary oviduct function in supporting fertilization and preimplantation development. Here we show that conditional knockout (cKO) mice lacking estrogen receptor α (ERα) epithelial cells have impaired due to a dramatic reduction sperm migration. In addition, all successfully fertilized eggs die before the 2-cell stage persistence...

Zinc is essential for many biological processes, including proper functioning of gametes. We recently reported that zinc levels rise by over 50% during oocyte maturation and attenuation availability this period could be achieved using the membrane-permeable heavy metal chelator N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN). This insufficiency resulted in formation large polar bodies, failure to establish metaphase II arrest, impaired establishment cortical polarity. As these...

Meiosis in mammalian females is marked by two arrest points, at prophase I and metaphase II, which must be tightly regulated order to produce a haploid gamete the time of fertilization. The transition metal zinc has emerged as necessary dynamic regulator establishment, maintenance, exit from II arrest, but roles during are largely unknown. In this study, we investigate mechanisms regulation first meiotic arrest. Disrupting availability arrested oocyte treatment with heavy chelator...

Abstract In sexual reproduction, sperm contribute half the genomic material required for creation of offspring yet core molecular mechanisms essential their formation are undefined. Here, α-arrestin molecule arrestin-domain containing 5 (ARRDC5) is identified as an regulator mammalian spermatogenesis. Multispecies testicular tissue transcriptome profiling indicates that expression Arrdc5 testis enriched, if not specific, in mice, pigs, cattle, and humans. Knockout mice leads to male specific...

Initiation of mouse embryonic development depends upon a series fertilization-induced rises in intracellular Ca2+. Complete egg activation requires influx extracellular Ca2+; however, the channels that mediate this remain unknown. Here we tested whether T-type channel CaV3.2, encoded by Cacna1h, mediates Ca2+ entry into oocytes. We show eggs express robust voltage-activated current is completely absent Cacna1h−/− eggs. females have reduced litter sizes, and careful analysis oscillation...

Significance At fertilization, repetitive calcium signals are induced in mammalian eggs that essential for activating embryo development. These supported by influx from the surrounding medium. Two ion channels supporting into eggs, Ca V 3.2 and TRPV3, were identified previously. Here we find a third channel, TRPM7, is this function. In absence of both TRPM7 3.2, fertilizing sperm stop prematurely. Female mice carrying lacking subfertile. Because channel function modulated ions culture...

Understanding factors that regulate zygotic genome activation (ZGA) is critical for determining how cells are reprogrammed to become totipotent or pluripotent. There limited information regarding this process occurs physiologically in early mammalian embryos. Here, we identify a mediator complex subunit, MED13, as translated during mouse oocyte maturation and transcribed from the genome. Knockdown conditional knockout approaches demonstrate MED13 essential ZGA mouse, part by regulating...

The estrogen receptor-alpha (ERalpha) acts through multiple pathways, including response element (ERE)-dependent (classical) and ERE-independent (nonclassical) mechanisms. We previously created a mouse model harboring two-amino-acid mutation of the DNA-binding domain (E207A, G208A) that precludes direct binding ERalpha to an ERE. After crossing heterozygous mutant mice with knockout (ERKO) line, it was possible assess degree physiological rescue by isolated nonclassical allele (-/AA; AA)...

Fully grown oocytes in the ovary are arrested at prophase of meiosis I because high levels intraoocyte cAMP that maintain increased cAMP-dependent protein kinase (PKA) activity. Following luteinizing hormone surge time ovulation, drop, resulting a reduction PKA activity triggers meiotic resumption. Although much is known about molecular mechanisms how fluctuations initiate oocyte's reentry into meiosis, significantly less requirement for oocyte after exit from arrest. Here we show although...

Cysteine-rich secretory protein 1 (CRISP1) is a glycoprotein produced by the rat epididymal epithelium in two forms, referred to as proteins D and E. CRISP1 has been implicated sperm-egg fusion shown suppress capacitation sperm. Several studies have suggested that associates transiently with sperm surface, whereas others at least portion of persists on surface. In present study, we demonstrate surface concentration-dependent manner, exhibiting saturable binding both caput cauda concentration...

During oocyte maturation, capacity and sensitivity of Ca2+ signaling machinery increases dramatically, preparing the metaphase II (MII)-arrested egg for fertilization. Upon sperm-egg fusion, release from IP3-sensitive endoplasmic reticulum stores results in cytoplasmic oscillations that drive activation initiate early embryo development. Premature can cause parthenogenetic prior to fertilization; thus, preventing inappropriate is critical ensuring robust MII arrest. Here, we show regulator...

Abstract The epithelial cell lining of the oviduct plays an important role in oocyte pickup, sperm migration, preimplantation embryo development, and transport. layer comprises ciliated nonciliated secretory cells. ciliary function has been shown to support gamete movement oviduct, yet not well characterized. Therefore, our goal was generate a cell-specific Cre recombinase mouse model study oviductal A knock-in model, Ovgp1Cre:eGFP, created by expressing from endogenous Ovgp1 (oviductal...

Summary Objective Corticosteroids can be synthesized in extra‐adrenal tissues but the contribution of this to circulating levels humans is not known. Previous vitro studies suggest that ‘hybrid’ corticosteroid 18‐oxocortisol (18‐oxoF) produced from cortisol by aldosterone synthase. We looked for evidence production and other corticosteroids 10 subjects stable on long‐term glucocorticoid replacement following bilateral adrenalectomy. Methods In phase 1, patients were maintained alone (30...

Zinc is an essential cofactor in hundreds of molecules needed for many biological processes, including formation and maturation gametes. Our laboratory has recently demonstrated important role zinc during oocyte meiotic maturation. The first division normally asymmetric produces a large much smaller polar body. However, the attenuation intracellular availability vitro mouse oocytes using membrane permeable heavy metal chelator N,N,N',N'-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN) causes...

Kallikreins (KLKs) are serine peptidases. It was established that

Abstract Calcium (Ca 2+ ) signals triggered at fertilization initiate resumption of the cell cycle and initial steps embryonic development. In mammals, sperm factor phospholipase Cζ triggers release Ca from endoplasmic reticulum (ER), initiating an oscillatory pattern transients that is modulated by egg factors including influx channels, transporters, phosphoinositide‐regulating enzymes. Here we compared characteristics oscillations following in vitro (IVF) ER stores among nine common...

Initiation of mouse embryonic development depends upon a series fertilization-induced rises in intracellular Ca(2+). Complete egg activation requires influx extracellular Ca(2+); however, the channels that mediate this remain unknown. Here, we tested whether α1 subunit T-type channel CaV3.2, encoded by Cacna1h, mediates Ca(2+) entry into oocytes. We show eggs express robust voltage-activated current is completely absent Cacna1h(-/-) eggs. females have reduced litter sizes, and careful...

Mol. Reprod. Dev. 80: 504–507, 2013. © 2013 Wiley Periodicals, Inc. This article is a US government work and, as such, in the public domain United States of America.

Spermatogenesis is a tightly regulated process in which germ cells progress through differentiation starting with spermatogonial stem (SSCs) and undifferentiated spermatogonia ending mature spermatozoa. has been described as three main phases: proliferation, meiosis differentiation. In normal mouse testis, neonatal cells, called gonocytes, migrate to the basement membrane of testis cord, where they are engulfed by Sertoli shortly after birth. Only few gonocytes that line cords maintain their...

Clinical Endocrinology, 66, 659–665 The publisher would like to apologise for the incorrect initials of two authors in article above.1 concerned are R. Bernhardt and M. Ingram. corrected reference is listed below: