scholarly journals Efforts to Generate a Male Contraception Just by Prevention of Sperm Motility Acquirement in Epididymis Without Influencing the Physiology of Spermatogenesis: Yet Still a Little Far Goal

2021 ◽  
pp. 1-3
Author(s):  
Kulvinder Kochar Kaur ◽  
Gautam Allahbadia ◽  
Mandeep Singh
Keyword(s):  
Sperm Motility ◽  
Protein Phosphatase ◽  
Semen Quality ◽  
Glycogen Synthase ◽  
Human Sperm ◽  
Female Reproductive Tract ◽  
World Population ◽  
Contraceptive Methods ◽  
Anchor Protein ◽  
Male Contraceptive

In view of the world population escalating at an alarming rate anticipated population will reach 9.8 billion by 2050. In contrast to female contraceptive measures male contraceptive methods are relatively negligible. Maximum researchers have concentrated on generation of male contraceptive methods by trying to modulate hormones but had to abandon this strategy as the pharmaceutical companies were not happy in view of marked adverse actions. Maximum nonhormonal strategies in research concentrate on spermatogenesis repression or reversible physical barriers. Sperm motility represents one of the maximum significant markers of semen quality as it is necessary for sperm motion appropriately in the female reproductive tract for it to arrive intricately towards the egg as well as fertilize it. The group of Vijayraghavan S, et al. have been concentrating on generation of a male contraceptive by utilization of targeting sperm motility at epididymal level by extensively studying the regulation of flaggelar protein motion by various subunits like Protein Phosphatase 1 (PP1), Protein Phosphatase Inhibitor-2 (PPPIR2), its phosphorylation by Glycogen Synthase Kinase-3 (GSK3), A kinase anchor protein 4(AKAP4). Recently they attempted to generate a bioportide that could simulate binding of the anchor protein AKAP4 that had been earlier revealed as a PPγ2 interactor in human sperm,that are implicated in sperm motility .Unfortunately that did not abolish sperm motility completely .This seemed to be surprising as PP1/ PPPIR2crosstalk seems to be central in regulation of sperm motility. Thus Silva et al., pointed that evaluation of the probable part of PPPIR7 as well as PPPIR11 in the manipulation of sperm motility in men might be the aim of future studies that needs to be continued to get more insight in this field.

Engineering sperm-binding IgG antibodies for the development of an effective nonhormonal female contraception

2021 ◽  
Vol 13 (606) ◽  
pp. eabd5219
Author(s):  
Bhawana Shrestha ◽  
Alison Schaefer ◽  
Yong Zhu ◽  
Jamal Saada ◽  
Timothy M. Jacobs ◽  
...  
Keyword(s):  
Biomedical Applications ◽  
Reproductive Tract ◽  
Human Sperm ◽  
Female Reproductive Tract ◽  
Infertile Woman ◽  
Igg Antibodies ◽  
Contraceptive Methods ◽  
Sperm Binding ◽  
Polyvalent Immunoglobulins ◽  
Unique Surface

Many women risk unintended pregnancy because of medical contraindications or dissatisfaction with contraceptive methods, including real and perceived side effects associated with the use of exogenous hormones. We pursued direct vaginal delivery of sperm-binding monoclonal antibodies (mAbs) that can limit progressive sperm motility in the female reproductive tract as a strategy for effective nonhormonal contraception. Here, motivated by the greater agglutination potencies of polyvalent immunoglobulins but the bioprocessing ease and stability of immunoglobulin G (IgG), we engineered a panel of sperm-binding IgGs with 6 to 10 antigen-binding fragments (Fabs), isolated from a healthy immune-infertile woman against a unique surface antigen universally present on human sperm. These highly multivalent IgGs (HM-IgGs) were at least 10- to 16-fold more potent and faster at agglutinating sperm than the parent IgG while preserving the crystallizable fragment (Fc) of IgG that mediates trapping of individual spermatozoa in mucus. The increased potencies translated into effective (>99.9%) reduction of progressively motile sperm in the sheep vagina using as little as 33 μg of the 10-Fab HM-IgG. HM-IgGs were produced at comparable yields and had identical thermal stability to the parent IgG, with greater homogeneity. HM-IgGs represent not only promising biologics for nonhormonal contraception but also a promising platform for engineering potent multivalent mAbs for other biomedical applications.

Functional studies of eppin

2011 ◽  
Vol 39 (5) ◽  
pp. 1447-1449 ◽  
Author(s):  
Michael G. O'Rand ◽  
Esther E. Widgren ◽  
Katherine G. Hamil ◽  
Erick J. Silva ◽  
Richard T. Richardson
Keyword(s):  
Sperm Motility ◽  
Specific Antigen ◽  
Human Sperm ◽  
Native Form ◽  
Calculated Molecular Mass ◽  
Consensus Sequences ◽  
Male Contraceptive ◽  
Functional Studies ◽  
Cysteine Rich Protein ◽  
Antimicrobial Protection

Our laboratory has characterized EPPIN [epididymal protease inhibitor; SPINLW1] as a novel gene on human chromosome 20q12-13.2, which encodes a cysteine-rich protein of 133 amino acids with a calculated molecular mass of 15.283 kDa, containing both Kunitz-type and WAP (whey acidic protein)-type four-disulfide core consensus sequences. Eppin is secreted by Sertoli cells in the testis and epididymal epithelial cells; it is predominantly a dimer, although multimers often exist, and in its native form eppin is found on the human sperm surface complexed with LTF (lactotransferrin) and clusterin. During ejaculation SEMG (semenogelin) from the seminal vesicles binds to the eppin protein complex, initiating a series of events that define eppin's function. Eppin's functions include (i) modulating PSA (prostate-specific antigen) enzyme activity, (ii) providing antimicrobial protection and (iii) binding SEMG thereby inhibiting sperm motility. As PSA hydrolyses SEMG in the ejaculate coagulum, spermatozoa gain progressive motility. We have demonstrated that eppin is essential for fertility because immunization of male monkeys with recombinant eppin results in complete, but reversible, contraception. To exploit our understanding of eppin's function, we are developing compounds that inhibit eppin–SEMG interaction and mimic anti-eppin, inhibiting sperm motility. These compounds should have potential as a male contraceptive.

scholarly journals Sperm Motility Development in the Epididymis is Associated with Decreased Glycogen Synthase Kinase-3 and Protein Phosphatase 1 Activity1

1996 ◽  
Vol 54 (3) ◽  
pp. 709-718 ◽  
Author(s):  
Srinivasan Vijayaraghavan ◽  
Donald T. Stephens ◽  
Kevin Trautman ◽  
Gary D. Smith ◽  
Balwant Khatra ◽  
...  
Keyword(s):  
Sperm Motility ◽  
Protein Phosphatase ◽  
Glycogen Synthase ◽  
Protein Phosphatase 1 ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3

Regulation of glycogen synthase and protein phosphatase-1 by hexosamines

Diabetes ◽  
1996 ◽  
Vol 45 (3) ◽  
pp. 322-327 ◽  
Author(s):  
E. D. Crook ◽  
D. A. McClain
Keyword(s):  
Protein Phosphatase ◽  
Glycogen Synthase ◽  
Protein Phosphatase 1

scholarly journals HSP105 Recruits Protein Phosphatase 2A To Dephosphorylate β-Catenin

2015 ◽  
Vol 35 (8) ◽  
pp. 1390-1400 ◽  
Author(s):  
Nancy Yu ◽  
Michael Kakunda ◽  
Victoria Pham ◽  
Jennie R. Lill ◽  
Pan Du ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Target Gene ◽  
Target Genes ◽  
Glycogen Synthase ◽  
Protein Phosphatase 2A ◽  
Breast Cancer Patients ◽  
Poor Overall Survival ◽  
Protein Levels ◽  
Phosphatase 2A ◽  
Unidentified Component

The Wnt/β-catenin pathway causes accumulation of β-catenin in the cytoplasm and its subsequent translocation into the nucleus to initiate the transcription of the target genes. Without Wnt stimulation, β-catenin forms a complex with axin (axis inhibitor), adenomatous polyposis coli (APC), casein kinase 1α (CK1α), and glycogen synthase kinase 3β (GSK3β) and undergoes phosphorylation-dependent ubiquitination. Phosphatases, such as protein phosphatase 2A (PP2A), interestingly, also are components of this degradation complex; therefore, a balance must be reached between phosphorylation and dephosphorylation. How this balance is regulated is largely unknown. Here we show that a heat shock protein, HSP105, is a previously unidentified component of the β-catenin degradation complex. HSP105 is required for Wnt signaling, since depletion of HSP105 compromises β-catenin accumulation and target gene transcription upon Wnt stimulation. Mechanistically, HSP105 depletion disrupts the integration of PP2A into the β-catenin degradation complex, favoring the hyperphosphorylation and degradation of β-catenin. HSP105 is overexpressed in many types of tumors, correlating with increased nuclear β-catenin protein levels and Wnt target gene upregulation. Furthermore, overexpression of HSP105 is a prognostic biomarker that correlates with poor overall survival in breast cancer patients as well as melanoma patients participating in the BRIM2 clinical study.

Use of laptop computers connected to internet through Wi-Fi decreases human sperm motility and increases sperm DNA fragmentation

2012 ◽  
Vol 97 (1) ◽  
pp. 39-45.e2 ◽  
Author(s):  
Conrado Avendaño ◽  
Ariela Mata ◽  
César A. Sanchez Sarmiento ◽  
Gustavo F. Doncel
Keyword(s):  
Dna Fragmentation ◽  
Sperm Motility ◽  
Human Sperm ◽  
Sperm Dna Fragmentation ◽  
Laptop Computers ◽  
Sperm Dna

TROPHININ-BINDING PEPTIDE, GWRQ, PROMOTES HUMAN SPERM MOTILITY

2008 ◽  
Vol 179 (4S) ◽  
pp. 620-620
Author(s):  
Shingo Hatakeyama ◽  
Noritaka Kamimura ◽  
Takuya Koie ◽  
Kazuyuki Mori ◽  
Yasuhiro Hashimoto ◽  
...  
Keyword(s):  
Sperm Motility ◽  
Human Sperm ◽  
Binding Peptide

Human sperm superoxide anion generation and correlation with semen quality in patients with male infertility

2004 ◽  
Vol 82 (4) ◽  
pp. 871-877 ◽  
Author(s):  
T SAID ◽  
A AGARWAL ◽  
R SHARMA ◽  
E MASCHA ◽  
S SIKKA ◽  
...  
Keyword(s):  
Male Infertility ◽  
Superoxide Anion ◽  
Semen Quality ◽  
Human Sperm ◽  
Superoxide Anion Generation

scholarly journals Antifertility Actions of a-Chlorohydrin in the Male

1983 ◽  
Vol 36 (4) ◽  
pp. 333 ◽  
Author(s):  
A RJones
Keyword(s):  
Male Fertility ◽  
Human Sperm ◽  
Male Rat ◽  
Low Doses ◽  
Dose Regime ◽  
Male Contraceptive ◽  
The Past ◽  
High Doses ◽  
Species Specific ◽  
Daily Oral Administration

Non-steroidal chemicals that affect male fertility have been known for over 25 years but only one compound, oc-chlorohydrin, possesses most of the attributes of an ideal male contraceptive. In the male rat, for example, continuous daily oral administration of low doses produces an almost immediate and continuous antifertility response that ceases when treatment is withdrawn. Such a dose regime does not interfere with libido, is apparently not toxic and the action is specific towards mature sperm. Furthermore, the action of the compound is species-specific: it is effective in the rat, ram, boar, guinea pig, hamster,rhesus monkey and upon ejaculated human sperm but it is ineffective in the mouse and the rabbit. High doses of oc-chlorohydrin can be neurotoxic, nephrotoxic and, in rats, lead to prolonged or permanent infertility. However, the antifertility response and the toxicity of racemic oc-chlorohydrin may be due, respectively, to the separate enantiomers. No other antifertility chemical has been investigated to such an extent as oc-chlorohydrin; this article reviews the progress that has been achieved with oc-chlorohydrin during the past six years.

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