In the mammalian ovary, progressive activation of primordial follicles from dormant pool serves as source fertilizable ova. Menopause, or end female reproductive life, occurs when follicle is exhausted. However, molecular mechanisms underlying are poorly understood. We provide genetic evidence that in mice lacking PTEN (phosphatase and tensin homolog deleted on chromosome 10) oocytes, a major negative regulator phosphatidylinositol 3-kinase (PI3K), entire becomes activated. Subsequently, all...

To maintain the female reproductive lifespan, majority of ovarian primordial follicles are preserved in a quiescent state order to provide ova for later life. However, molecular mechanism that maintains long quiescence is poorly understood. Here we genetic evidence show tumor suppressor tuberous sclerosis complex 1 (Tsc1), which negatively regulates mammalian target rapamycin (mTORC1), functions oocytes follicles. In mutant mice lacking Tsc1 gene oocytes, entire pool activated prematurely...

The molecular mechanisms that control reproductive aging and menopausal age in females are poorly understood. Here, we provide genetic evidence 3-phosphoinositide-dependent protein kinase-1 (PDK1) signaling oocytes preserves lifespan by maintaining the survival of ovarian primordial follicles. In mice lacking PDK1-encoding gene Pdk1 oocytes, majority follicles depleted around onset sexual maturity, causing premature failure (POF) during early adulthood. We further showed suppressed...

To maintain the length of reproductive life in a woman, it is essential that most her ovarian primordial follicles are maintained quiescent state to provide continuous supply oocytes. However, our understanding molecular mechanisms control quiescence and activation still its infancy. In this study, we some genetic evidence show tumor suppressor tuberous sclerosis complex 2 (Tsc2), which negatively regulates mammalian target rapamycin 1 (mTORC1), functions oocytes dormancy follicles. mutant...

It has been generally accepted for more than half a century that, in most mammalian species, oocytes cannot renew themselves postnatal or adult life, and that the number of is already fixed fetal neonatal ovaries. This assumption, however, challenged over past decade. In this study, we have taken an endogenous genetic approach to question generated multiple fluorescent Rosa26(rbw/+);Ddx4-Cre germline reporter mouse model vivo vitro tracing development female cell lineage. Through live...

Mammalian oocytes are arrested at the prophase of meiosis I during fetal or postnatal development, and is resumed by preovulatory surge luteinizing hormone. The in vivo functional roles cyclin-dependent kinases (Cdks) resumption mammalian largely unknown. Previous studies have shown that deletions Cdk3, Cdk4 Cdk6 mice result viable animals with normal oocyte maturation, indicating these Cdks not essential for meiotic maturation oocytes. In addition, conventional knockout Cdk1 Cdk2 leads to...

Immature ovarian primordial follicles are essential for maintenance of the reproductive lifespan female mammals. Recently, it was found that overactivation phosphatidylinositol 3-kinase (PI3K) signaling in oocytes by an oocyte-specific deletion Pten (phosphatase and tensin homolog deleted on chromosome ten), gene encoding PI3K negative regulator PTEN, results premature activation entire pool follicles, indicating pathway is important control follicular activation. To investigate whether...

Mitochondria are highly dynamic organelles and their distribution, structure activity affect a wide range of cellular functions. Mitochondrial membrane potential (∆Ψm) is an indicator mitochondrial plays major role in ATP production, redox balance, signaling metabolism. Despite the absolute reliance oocyte early embryo development on function, there little known about spatial temporal aspects ΔΨm during maturation. The one exception that previous findings using indicator, JC-1, report...

Do mitochondria-targeted therapies reverse ageing- and oxidative stress-induced spindle defects in oocytes from mice humans?Exposure to MitoQ or BGP-15 during IVM protected against chromosomal mouse exposed stress derived reproductively aged whilst promoted nuclear maturation misalignments human oocytes.Spindle abnormalities are more prevalent with maternal aging, increasing the risk of aneuploidy, miscarriage genetic disorders such as Down's syndrome. The origin compromised oocyte function...

Although the genetic triggers for gonadal sex differentiation vary across species, cell biology of development was long thought to be largely conserved. Here, we present a comprehensive analysis differentiation, using single-cell sequencing in embryonic chicken gonad during sexual differentiation. The data show that embryonic-supporting cells do not derive from coelomic epithelium, contrast other vertebrates studied. Instead, they DMRT1+/PAX2+/WNT4+/OSR1+ mesenchymal population. We find...

Abstract The development of oocytes and early embryos is dependent on mitochondrial ATP production. This reliance activity, together with the exclusively maternal inheritance mitochondria in development, places as central regulators both fertility transgenerational mechanisms. Mitochondrial mass mtDNA content massively increase during oocyte growth. They are highly dynamic organelles maturation accompanied by trafficking around subcellular compartments. Due to their key roles generation...

Background Primordial ovarian follicles, which are often present in the ovaries of premature failure (POF) patients or cryopreserved from young cancer who undergoing gonadotoxic anticancer therapies, cannot be used to generate mature oocytes for vitro fertilization (IVF). There has been very little success triggering growth primordial follicles obtain fertilizable due poor understanding biology follicle activation. Methodology/Principal Findings We have recently reported that PTEN...

The majority of ovarian primordial follicles must be preserved in a quiescent state to allow for the regular production gametes over female reproductive lifespan. However, molecular mechanism that maintains long quiescence is poorly understood. Under certain pathological conditions, entire pool matures simultaneously leading an accelerated loss and premature failure (POF). We have previously shown Pten (phosphatase tensin homolog deleted on chromosome ten) mouse oocytes leads activation...

BACKGROUND This study was designed to adapt the Elixhauser comorbidity index for 4 cancer‐specific populations (breast, prostate, lung, and colorectal) compare 3 versions of score (individual comorbidities, summary score, score) with Charlson predicting 2‐year survival types cancer. METHODS cohort used Texas Cancer Registry–linked Medicare data from 2005 2011 older patients diagnosed breast (n = 19,082), prostate 23,044), lung 26,047), or colorectal cancer 16,693). For each cohort, were...

Undernutrition is a leading cause of morbidity and mortality in children developing countries including Nepal. This study aimed to identify sociodemographic, environmental, maternal child health (MCH) factors associated with objectively assessed underweight among aged under 5 years Ilam district eastern Nepal.A community-based cross-sectional 300 mothers was conducted using interviewer-administered questionnaires from July August 2012. The sample derived by randomly selecting three village...

Assessment of First-Year Use Medicare's Advance Care Planning Billing CodesAdvance care planning (ACP) conversations occur infrequently among patients and their health professionals, when they do occur, the context is often a stressful clinical situation. 1,2 that too late (or not at all) can result in invasive, expensive, aligned with patients' wishes.To encourage professionals to initiate ACP discussions, Medicare began reimbursing for services on January 1, 2016, under separate billing...

Eggs contain about 200,000 mitochondria that generate adenosine triphosphate and metabolites essential for oocyte development. Mitochondria also integrate metabolism transcription via regulate epigenetic modifiers, but there is no direct evidence linking mitochondrial function to the maternal epigenome subsequent embryo Here, we have disrupted deletion of fission factor Drp1. Fission-deficient oocytes exhibit a high frequency failure in peri- postimplantation This associated with altered...

The molecular mechanisms underlying reproductive aging and menopausal age in female mammals are poorly understood. Mechanistic target of rapamycin complex 1 (mTORC1) is a central controller cell growth proliferation. To determine whether mTORC1 signaling oocytes plays direct role physiological follicular development fertility mice, we conditionally deleted the specific essential component Rptor (regulatory-associated protein mTORC1) from primordial follicles by using transgenic mice...

A unique feature of female germ cell development in mammals is their remarkably long arrest at the prophase meiosis I, which lasts up to 50 years humans. Both dormant and growing oocytes are arrested I completely lack ability resume meiosis. Here, we show that prolonged meiotic cells largely achieved via inhibitory phosphorylation Cdk1 (cyclin-dependent kinase 1). In two mouse models where have introduced mutant Cdk1T14AY15F cannot be inhibited by (Cdk1AF) small meiotically incompetent...

Little is known about variation in use of rehabilitation services provided acute care hospitals for people who have had a stroke. The objective was to examine patient and hospital sources This retrospective, cohort design. sample consisted Medicare fee-for-service beneficiaries with ischemic stroke admitted 2010. claims data were linked the Provider Services file gather information on characteristics American Community Survey sociodemographic data. Chi-square tests compared stratified by any...