Abstract:
OBJECTIVE:To design protein phosphatase 1 (PP1)-disrupting peptides covalently coupled to inert cell-penetrating peptides (CPPs) as sychnologically organized bioportide constructs as a strategy to modulate sperm motility. DESIGN:Experimental study. SETTING:Academic research laboratory. PATIENT(S)/ANIMAL(S):Normozoospermic men providing samples for routine analysis and Holstein Frisian bulls. INTERVENTION(S):None. MAIN OUTCOME MEASURE(S):Effect of the bioportides on the activity and interactions of PP1γ2-a PP1 isoform expressed exclusively in testicular germ cells and sperm-and on sperm vitality and motility. RESULT(S):PP1-disrupting peptides were designed based on the sequences from: 1) a sperm-specific PP1 interactor (A kinase anchor protein 4); and 2) a PP1 inhibitor (protein phosphatase inhibitor 2). Those sequences were covalently coupled to inert CPPs as bioportide constructs, which were successfully delivered to the flagellum of sperm cells to induce a marked impact on PP1γ2 activity and sperm motility. Molecular modeling studies further facilitated the identification of an optimized PP1-binding sequence and enabled the development of a modified stop-sperm bioportide with reduced size and increased potency of action. In addition, a bioportide mimetic of the unique 22-amino acid C-terminus of PP1γ2 accumulated within spermatozoa to significantly reduce sperm motility and further define the PP1γ2-specific interactome. CONCLUSION(S):These investigations demonstrate the utility of CPPs to deliver peptide sequences that target unique protein-protein interactions in spermatozoa to achieve a significant impact upon spermatozoa motility, a key prognostic indicator of male fertility.
journal_name
Fertil Steriljournal_title
Fertility and sterilityauthors
Silva JV,Freitas MJ,Santiago J,Jones S,Guimarães S,Vijayaraghavan S,Publicover S,Colombo G,Howl J,Fardilha Mdoi
10.1016/j.fertnstert.2020.08.013subject
Has Abstractpub_date
2020-09-22 00:00:00eissn
0015-0282issn
1556-5653pii
S0015-0282(20)30767-6pub_type
杂志文章abstract:OBJECTIVE:To study the regulatory mechanisms of selective intrauterine growth restriction (sIUGR) independent of confounding genetic factors, monochorionic (MC) twins are the ideal model, because they have identical genomic DNA. We hypothesize that the intrauterine growth restriction fetus has mitochondrial activation ...
journal_title:Fertility and sterility
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.fertnstert.2013.03.003
更新日期:2013-07-01 00:00:00
abstract:OBJECTIVE:To investigate the relative differences in outcomes among microdissection testicular sperm extraction (micro-TESE), conventional testicular sperm extraction (cTESE), and testicular sperm aspiration (TESA) in men with nonobstructive azoospermia. DESIGN:Systematic review and meta-analysis. SETTING:Outpatient ...
journal_title:Fertility and sterility
pub_type: 杂志文章,meta分析,评审
doi:10.1016/j.fertnstert.2015.07.1136
更新日期:2015-11-01 00:00:00
abstract:OBJECTIVE:To assess the single-dose pharmacokinetics of a recombinant human FSH preparation (Gonal-F; Laboratoires Serono, Aubonne, Switzerland), administered by i.v., IM, and SC routes and its pharmacokinetics at steady state after multiple dosing by the SC route. DESIGN:Twelve healthy down-regulated female volunteer...
journal_title:Fertility and sterility
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1994-04-01 00:00:00
abstract::There was no difference in the density of nerve fibers across the menstrual cycle in peritoneal endometriotic lesions. These findings may explain why patients with peritoneal endometriosis often have painful symptoms throughout the menstrual cycle. ...
journal_title:Fertility and sterility
pub_type: 杂志文章
doi:10.1016/j.fertnstert.2011.01.150
更新日期:2011-06-30 00:00:00
abstract::A randomized comparison trial was performed to evaluate whether follicular reaspiration with use of a double-lumen retrieval needle improves oocyte recovery when compared with direct follicular aspiration among low-responding patients undergoing ART. There were no differences observed in the number of oocytes retrieve...
journal_title:Fertility and sterility
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.fertnstert.2008.04.034
更新日期:2009-04-01 00:00:00
abstract:OBJECTIVE:To measure autoantibodies that recognize oxidatively modified proteins in the sera of women with surgically proven endometriosis. DESIGN:Prospective study. SETTING:Tertiary care academic medical center. PATIENT(S):Women undergoing surgery for endometriosis or tubal ligation. INTERVENTION(S):None. MAIN OU...
journal_title:Fertility and sterility
pub_type: 杂志文章
doi:10.1016/s0015-0282(99)00145-4
更新日期:1999-06-01 00:00:00
abstract:OBJECTIVE:Formin-2 (Fmn2) mutant mice produce oocytes with meiosis I arrest. Our aim was to describe the human FORMIN-2 (FMN2) gene and to identify DNA sequence polymorphisms in patients with unexplained infertility and multiple failed IVF cycles. DESIGN:Institutional review board-approved observational case-control s...
journal_title:Fertility and sterility
pub_type: 杂志文章
doi:10.1016/j.fertnstert.2004.10.051
更新日期:2005-05-01 00:00:00
abstract:OBJECTIVE:To evaluate the effects of conjugated equine estrogens, medroxyprogesterone acetate (MPA), conjugated equine estrogens combined with MPA, tamoxifen, and soybean estrogens on vaginal cytology in surgically postmenopausal cynomolgus macaques (Macaca fascicularis). DESIGN:Randomized long-term experimental trial...
journal_title:Fertility and sterility
pub_type: 杂志文章
doi:
更新日期:1996-05-01 00:00:00
abstract:OBJECTIVE:To evaluate the effect of lipopolysaccharide (LPS) on the expression of tumor necrosis factor alpha (TNFalpha) and interleukin-8 (IL-8) protein in endometriotic stromal cells (ESC) and their effect on the proliferation of ESC. DESIGN:Prospective study. SETTING:Department of Obstetrics and Gynecology, Tottor...
journal_title:Fertility and sterility
pub_type: 杂志文章
doi:10.1016/j.fertnstert.2004.04.038
更新日期:2004-10-01 00:00:00
abstract:OBJECTIVE:To describe laparoscopic management of a case of leyomiomatosis peritonealis disseminata associated with ovarian endometriosis. DESIGN:Surgical video article. SETTING:Academic hospital. PATIENT:We present a case of a 30-year-old woman referred to our clinic for abdominal and pelvic pain and dyspareunia. A ...
journal_title:Fertility and sterility
pub_type: 杂志文章
doi:10.1016/j.fertnstert.2019.03.023
更新日期:2019-06-01 00:00:00
abstract:OBJECTIVE:To determine if short-term weight change among women with unexplained infertility (UI) and polycystic ovary syndrome (PCOS) undergoing ovulation induction is associated with live birth. DESIGN:Secondary analysis of randomized trials. SETTING:Multicenter fertility trial sites. PATIENT(S):A total of 900 wome...
journal_title:Fertility and sterility
pub_type: 杂志文章
doi:10.1016/j.fertnstert.2020.06.002
更新日期:2020-11-01 00:00:00
abstract:OBJECTIVE:To investigate whether sphingosine-1-phosphate (S1P), an apoptosis-inhibitor, would be able to protect ovarian follicles from chemotherapy-induced cell death in vivo. DESIGN:Animal study. SETTING:Academic medical center. ANIMAL(S):Twenty female mice. INTERVENTION(S):Twenty mice were randomly assigned into...
journal_title:Fertility and sterility
pub_type: 杂志文章
doi:10.1016/j.fertnstert.2006.06.020
更新日期:2007-01-01 00:00:00
abstract::In the United States, approximately 650,000 women of reproductive age undergo tubal sterilization each year and some of these women later have hysterectomies. Little is known about risk factors for having hysterectomy after tubal sterilization. For examination of this issue, we analyzed data from the Collaborative Rev...
journal_title:Fertility and sterility
pub_type: 杂志文章
doi:10.1016/s0015-0282(16)48974-0
更新日期:1985-11-01 00:00:00
abstract::Most oocyte donation programs have experienced higher pregnancy rates than usually seen in regular in vitro fertilization (IVF), suggesting that the quality of either the oocytes or the endometrium is superior. To clarify this issue we analyzed the results of transfers of 136 cryopreserved embryos originating either f...
journal_title:Fertility and sterility
pub_type: 杂志文章
doi:10.1016/s0015-0282(16)53830-8
更新日期:1990-10-01 00:00:00
abstract:OBJECTIVE:The objective of the present studies was to determine whether luteinizing hormone (LH) depletes ascorbic acid in the preovulatory follicle. DESIGN:Controlled, prospective experimental study. SETTING:University-based research center. ANIMAL(S):Sprague-Dawley female rats. INTERVENTION(S):Follicular growth a...
journal_title:Fertility and sterility
pub_type: 杂志文章
doi:10.1016/s0015-0282(00)01550-8
更新日期:2000-11-01 00:00:00
abstract::The outcome of a series of pre-embryo transfers to 31 women with ovarian failure is described. Twenty six fertile women functioned as nonanonymous donors, providing oocytes for in vitro fertilization after undergoing controlled ovarian hyperstimulation and transvaginal ultrasound directed oocyte aspiration. Recipients...
journal_title:Fertility and sterility
pub_type: 杂志文章
doi:10.1016/s0015-0282(16)54055-2
更新日期:1991-01-01 00:00:00
abstract:OBJECTIVE:To investigate the expression pattern of proinflammatory, anti-inflammatory, and angiogenic cytokines and their effect on various mediators of endometrial receptivity in women with idiopathic recurrent spontaneous miscarriage (IRSM). DESIGN:A prospective study. SETTING:Tertiary care hospital and reproductiv...
journal_title:Fertility and sterility
pub_type: 杂志文章
doi:10.1016/j.fertnstert.2012.08.034
更新日期:2013-01-01 00:00:00
abstract:OBJECTIVE:To review our experience with low-dose IM methotrexate for the medical management of ectopic pregnancy (EP). DESIGN:Retrospective chart review. SETTING:Magee-Womens Hospital, Pittsburgh, Pennsylvania. PATIENT(S):The first 50 women treated by the resident service in whom EP was diagnosed and treated with me...
journal_title:Fertility and sterility
pub_type: 杂志文章
doi:10.1016/s0015-0282(97)00284-7
更新日期:1997-10-01 00:00:00
abstract:OBJECTIVE:To investigate the value of the ultrasonographically determined size of seminiferous tubules and other conventional parameters for predicting sperm retrieval by microdissection testicular sperm extraction (micro-TESE). DESIGN:Clinical retrospective study. SETTING:Two urological clinics. PATIENT(S):Eight hu...
journal_title:Fertility and sterility
pub_type: 杂志文章
doi:10.1016/j.fertnstert.2019.08.061
更新日期:2020-01-01 00:00:00
abstract:OBJECTIVE:To describe two cases of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) with testicular sperm in men with immotile cilia syndromes. DESIGN:Case report. SETTING:A university-based male infertility clinic and assisted reproduction unit. PATIENT(S):Two couples with male factor infert...
journal_title:Fertility and sterility
pub_type: 杂志文章
doi:10.1016/s0015-0282(01)01974-4
更新日期:2001-09-01 00:00:00
abstract:OBJECTIVE:To test the hypothesis that adrenal androgen (AA) secretion is an inherited trait in PCOS and that serum DHEAS concentrations, as a marker of AA secretion, will be correlated between women with PCOS and their sisters. DESIGN:Prospective case-control. SETTING:Tertiary care center. PATIENT(S):Sixty-two PCOS ...
journal_title:Fertility and sterility
pub_type: 杂志文章
doi:10.1016/j.fertnstert.2006.05.045
更新日期:2006-12-01 00:00:00
abstract:OBJECTIVE:To determine if endometrial tissue specific complement (C) activation occurs in patients with endometriosis. DESIGN:Prospective. SETTING:University of Oklahoma Health Sciences Center, a tertiary care referral center. PATIENTS:Twenty-six women, 9 with endometriosis and 17 without endometriosis. INTERVENTIO...
journal_title:Fertility and sterility
pub_type: 杂志文章
doi:
更新日期:1992-04-01 00:00:00
abstract::The objective of this retrospective cohort study was to assess the potential effects of preconceptional short-term exposure to particulate air pollution in a real-world situation on pregnancy outcome in infertile women evaluating the possible role of IVF/embryo transfer treatment on this outcome using women who had co...
journal_title:Fertility and sterility
pub_type: 杂志文章
doi:10.1016/j.fertnstert.2009.06.031
更新日期:2010-01-01 00:00:00
abstract::One hundred seventy-seven women aged 41 +/- 8 (mean +/- SD) years, referred for evaluation of excessive uterine bleeding, were enrolled in an open-label randomized trial to evaluate the efficacy of local anesthesia before hysteroscopy in an outpatient population. The patients underwent hysteroscopy and endometrial bio...
journal_title:Fertility and sterility
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1994-11-01 00:00:00
abstract:OBJECTIVE:To evaluate the results of IVF in women > or = 40 years of age using their own oocytes. DESIGN:Retrospective study. SETTING:Wolfson and Royal Masonic in vitro fertilization units, London, United Kingdom. PATIENT(S):A total of 1,087 IVF cycles were started in women > or = 40 years of age. INTERVENTION(S):M...
journal_title:Fertility and sterility
pub_type: 杂志文章
doi:10.1016/s0015-0282(98)00353-7
更新日期:1998-12-01 00:00:00
abstract:OBJECTIVE:To determine the level of standardization in performance of the semen analysis among clinical laboratories in the United States. DESIGN:A survey was mailed to laboratories requesting information about the laboratory and performance of the semen analysis. Responses were received from 536 laboratories. SETTIN...
journal_title:Fertility and sterility
pub_type: 杂志文章
doi:10.1016/s0015-0282(02)03296-x
更新日期:2002-09-01 00:00:00
abstract::The concentrations of pregnanediol-3-glucuronide (PGD) and pregnanolone (PN) were measured in daily morning urine specimens from 66 infertile women (40 with varying degrees of endometriosis and 26 control subjects) and correlated with daily changes in basal body temperature (BBT) and with midluteal levels of serum pro...
journal_title:Fertility and sterility
pub_type: 杂志文章
doi:
更新日期:1983-11-01 00:00:00
abstract:OBJECTIVE:To measure IVF effectiveness, which is defined as the cumulative incidence of live delivery over real time in women after commencing IVF treatment. DESIGN:Population-based retrospective cohort study. SETTING:IVF clinics in Western Australia (WA). PATIENT(S):All women ages 20-44 years inclusive at start of ...
journal_title:Fertility and sterility
pub_type: 杂志文章
doi:10.1016/j.fertnstert.2011.01.130
更新日期:2011-04-01 00:00:00
abstract:OBJECTIVE:To compare the rate of chromosome abnormalities in embryos obtained from karyotypically normal patients with nonobstructive azoospermia undergoing testicular sperm extraction (TESE) to those from patients undergoing intracytoplasmic sperm injection (ICSI) with ejaculated sperm. DESIGN:Retrospective analysis....
journal_title:Fertility and sterility
pub_type: 杂志文章
doi:10.1016/s0015-0282(02)04407-2
更新日期:2003-01-01 00:00:00
abstract:OBJECTIVE:To compare in vitro fertilization (IVF) outcomes between fresh embryo transfer (ET) and frozen-thawed ET (the "freeze-all" policy), with fresh ET performed only in cases without progesterone (P) elevation. DESIGN:Prospective, observational, cohort study. SETTING:Private IVF center. PATIENT(S):A total of 53...
journal_title:Fertility and sterility
pub_type: 杂志文章
doi:10.1016/j.fertnstert.2015.01.045
更新日期:2015-05-01 00:00:00