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Archive for the ‘Reproductive Andrology, Embryology, Genomic Endocrinology, Preimplantation Genetic Diagnosis and Reproductive Genomics’ Category

A genetic switch to control female sexual behavior

Posted in Behavior, Behavioral Genetics, Biological Networks, Gene Regulation and Evolution, Cell Biology, Cell Biology, Signaling & Cell Circuits, CRISPR/Cas9 & Gene Editing, Developmental biology, Genomic Endocrinology, Reproductive Andrology, Embryology, Genomic Endocrinology, Preimplantation Genetic Diagnosis and Reproductive Genomics, Reproductive Biology & Bio Instrumentation, Signaling & Cell Circuits, tagged , , , , , on May 16, 2016| Leave a Comment »

A Genetic Switch to Control Female Sexual Behavior, Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 2: CRISPR for Gene Editing and DNA Repair

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

In an African cichlid fish, Astatotilapia burtoni, fertile females select a mate and perform a stereotyped spawning / mating routine, offering quantifiable behavioral outputs of neural circuits. A male fish attracts a fertile female by rapidly quivering his brightly colored body. If she chooses him, he guides her back to his territory, where he quivers some more as she pecks at fish egg–colored spots on his anal fin. Next, she lays eggs and quickly scoops them up in her mouth. With a mouthful of eggs, she continues pecking at the male’s spots, “believing” them to be eggs to be collected. As she does, he releases sperm from near his anal fin, which she also gathers. This fertilizes the eggs, and she carries the embryos in her mouth for two weeks as they develop.

 

But, the question was how these females can time their reproduction to coincide with when they are fertile. The female fish will not approach or choose males until they are ready to reproduce, so there must be something in their brains that signals when sexual behavior will be required. The scientists began by considering signaling molecules previously associated with sexual behavior and reproduction, and showed that PGF2α injection activates a naturalistic pattern of sexual behavior in female Astatotilapia burtoni. They would engage in mating behavior even if they were non-fertile, doing the quiver dance with males, but wouldn’t actually lay eggs since they had none.

 

The scientists also identified cells in the brain that transduce the prostaglandin signal to mate and showed that the gonadal steroid 17α, 20β-dihydroxyprogesterone modulates mRNA levels of the putative receptor for PGF2α. The scientists keyed in on a receptor for PGF2α in the preoptic area (POA) within the hypothalamus of the brain, a region involved in sexual behavior across animals. They suspected that when PGF2α levels elevated in the fish, the molecule attaches to this receptor and triggers sexual behavior. Then they used CRISPR/Cas9 to generate PGF2α receptor knockout fish. This gene deletion or knockout uncoupled the sexual behavior from fertility status to prove that the receptor of PGF2α is necessary for the initiation of sexual behavior.

 

The finding has parallels across all vertebrates, and might influence the understanding of social behavior in humans. The next steps for this work will involve understanding other behaviors that are regulated by this receptor, and the finding provides insight into both the evolution of reproduction and sexual behaviors. In mammals and other vertebrates, PGF2α promotes the onset of labor and motherly behaviors, and this present research, coupled with other studies, suggests that PGF2α signaling has a common ancestral function associated with birth and its related behaviors.

 

References:

 

http://www.ncbi.nlm.nih.gov/pubmed/26996507

 

http://news.stanford.edu/news/2016/march/fish-mating-behavior-031716.html

 

 

http://www.academia.edu/676252/The_Genetics_of_Female_Sexual_Behaviour

 

https://scifeeds.com/news/scientists-identify-genetic-switch-for-female-sexual-behavior/

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Cellular switch molecule for sperm motility control: a novel target for male contraception and infertility treatments

Posted in Biomarkers & Medical Diagnostics, Ca2+ triggered activation, Calcium Signaling, Cell Biology, Cell Biology, Signaling & Cell Circuits, Clinical Diagnostics, Endocrine Diseases, Population Health Management, Reproductive Andrology, Embryology, Genomic Endocrinology, Preimplantation Genetic Diagnosis and Reproductive Genomics, Reproductive Biology & Bio Instrumentation, Signaling, Signaling & Cell Circuits, tagged , , , , , on April 4, 2016| Leave a Comment »

Cellular switch molecule for sperm motility control: a novel target for male contraception and infertility treatments

Reporter and Curator: Sudipta Saha, Ph.D.

 

Researchers have discovered the cellular switch that boosts the activity of sperm cells so that they can travel to the egg.  The finding may lead to new options for male contraception as well as treatments for infertility resulting from problems with sperm mobility.

Inside the male reproductive tract, mature sperm are capable of limited movement. This limited movement, however, is not enough to propel them toward the egg when they enter the female reproductive tract. To begin their journey, they must first be activated by the hormone progesterone, which is released by the egg.

The researchers reported that the molecule to which progesterone must bind is the enzyme alpha/beta hydrolase domain containing protein 2 (ABHD2), found in the sperm cell’s outer membrane. Similarly, strategies to bypass or enhance the enzyme might provide therapies for treating infertility resulting from sperm that lack movement capability.

Before a sperm can transition to the hyper-active phase, calcium must pass through the cell’s outer membrane and enter the flagella, the tail-like appendage the cell uses to propel itself. The sperm protein known as CatSper joins with similar proteins in the flagella to allow the entry of calcium.

When the researchers undertook the current study, it was not known whether progesterone interacted directly with CatSper to trigger the calcium influx, or acted on some other molecule (which, in turn, acted on CatSper). Before treating sperm with progesterone, the researchers exposed them to a chemical that inhibits a particular class of enzymes that they believed could include the candidate molecule that acted on CatSper. The hunch proved correct: the treated cells remained inactive after progesterone exposure, indicating that CatSper was not directly involved.

Working with modified progesterone, the researchers eventually isolated ABHD2 from the sperm tails. When the researchers inactivated ABHD2, exposure to progesterone failed to activate the sperm cells, confirming that ABHD2 is the molecular target for progesterone.

All of the technical terminology aside, this means that the researchers have pinned down the cellular switch that boosts the sperm along to the egg, so by blocking the ABHD2 activity, new male birth control methods could be on the way. Conversely, enhancing the enzyme could lead to new treatments for male infertility.

It will be interesting to see how this discovery impacts future research concerning male birth control and infertility treatments. Perhaps it’s the missing piece of information that will quickly yield an effective new male contraception option.

 

SOURCES

http://www.nih.gov/news-events/news-releases/researchers-identify-molecule-needed-sperm-activation

http://www.ncbi.nlm.nih.gov/pubmed/26989199

http://thescienceexplorer.com/brain-and-body/nih-funded-study-made-breakthrough-discovery-could-lead-new-male-birth-control

http://www.jhunewsletter.com/2016/03/31/researchers-find-a-protein-fertilization-catalyst/

 

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Testosterone treatment improved primarily sexual function than walking or vitality in older men with low testosterone levels

Posted in Biomarkers & Medical Diagnostics, Cell Biology, Cell Biology, Signaling & Cell Circuits, Chemical Biology and its relations to Metabolic Disease, Clinical Diagnostics, Disease Biology, Regenerative Biology and Medicine, Reproductive Andrology, Embryology, Genomic Endocrinology, Preimplantation Genetic Diagnosis and Reproductive Genomics, tagged , , , , , on March 18, 2016| Leave a Comment »

Testosterone treatment improved primarily sexual function than walking or vitality in older men with low testosterone levels

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

A preliminary study of testosterone therapy in older men with low levels of the hormone and clinical conditions to which low testosterone might contribute, found that restoring levels to those of healthy young men improved sexual function. Treatment had a smaller effect on other aspects of health, such as the ability to walk or the sense of vitality.

 

A high proportion of older men have testosterone levels well below those found in healthy younger men. In most cases, these low levels are not due to diseases known to affect testosterone levels, such as testicular or pituitary conditions. Many of these men also have symptomatic problems that could be related to low testosterone, including diminished sexual function, decreased mobility and fatigue.

 

For a long time, there has been interest in whether testosterone is an appropriate therapy for aging-related conditions in men. This study clarifies questions about some of its potential benefits. The study did not find a pattern of increased cardiovascular disease risk. Clarifying the risks requires further study.

 

Participants included 790 men age 65 and older with serum testosterone levels consistently well below the average for young healthy men. They were randomized to receive testosterone gel applied to the skin or a placebo gel daily. Serum testosterone concentration was measured at one, two, three, six, nine and 12 months. The men were also closely monitored for prostate and cardiovascular problems. In addition to low testosterone, the presence of at least one of three conditions (low sexual function, difficulty in walking or low vitality) was required for eligibility to participate in the T Trials (Testosterone Trials).

 

  • Sexual function — In men with low sexual function, testosterone treatment increased sexual activity, sexual desire and erectile function more than placebo treatment.

 

  • Physical function — In men with difficulty in walking, testosterone treatment did not significantly affect walking ability, as measured by the distance they could walk in six minutes (a common test of walking ability). However, in all men, walking speed and distance did improve among those who received testosterone compared with placebo.

 

  • Vitality — In the group of men with symptoms of low vitality and fatigue, testosterone treatment did not significantly affect fatigue symptoms, but had modest favorable effects on mood.

 

The trials’ results indicate that, for older men with low sexual function, testosterone treatment can contribute to improved function. In contrast, though, the results don’t indicate that testosterone treatment for older men with low walking ability or vitality will improve these conditions to a great extent. Older men should consult their physicians if considering a testosterone treatment.

 

References:

 

http://www.nih.gov/news-events/news-releases/nih-supported-trials-test-hormonal-therapy-older-men-low-testosterone-levels

 

http://www.uptodate.com/contents/overview-of-testosterone-deficiency-in-older-men

 

http://www.mayoclinic.org/healthy-lifestyle/sexual-health/in-depth/testosterone-therapy/art-20045728

 

http://www.webmd.com/men/features/low-testosterone-explained-how-do-you-know-when-levels-are-too-low

 

http://www.healthline.com/health/side-effects-of-low-testosterone

 

http://www.health.harvard.edu/mens-health/hormone-replacement-the-male-version

 

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Spermatogenic Defects in Sex Reversed Mice

Posted in Cell Biology, Clinical Genomics, Population Health Management, Genetics & Pharmaceutical, Reproductive Andrology, Embryology, Genomic Endocrinology, Preimplantation Genetic Diagnosis and Reproductive Genomics, Uncategorized, tagged , , , , , , , on February 29, 2016| Leave a Comment »

Spermatogenic Defects in Sex Reversed Mice

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

“Sex reversed” (Sxr) is an inherited form of sex reversal that causes XX and XO mice to develop as phenotypically normal males. Adult XYSxra mice exhibit varying degrees of spermatogenic deficiency but are usually fertile, while XOSxra mice have severe spermatogenic failure and are always sterile. The present quantitative spermatogenic analysis reports when these anomalies first appear during puberty. The results demonstrate that in XYSxra mice there was increased degeneration of pachytene spermatocytes and, to a lesser extent, meiotic metaphase stages. On average, there were only one-half the number of spermatids compared with the XY controls. The defect in XOSxra mice appeared a little later, with an almost complete arrest and degeneration during the meiotic metaphases.

 

A minority of XYSxra mice are sterile, and these may have testes as small as those from XOSxra mice. Adult XOSxra mice have consistently small testes and are invariably sterile. The reported results document the testicular defects in XYSxra and XOSxra testes as they first arise during puberty. The only other quantitative data on XYSxra and XOSxra spermatogenesis are for adult mice. A previous report described XYSxra testes as being a “mosaic” of normal and defective spermatogenesis. Recently a more extensive analysis was carried out of adult XYSxra and XOSxra testes. Once again there is good agreement with the present results in that the spermatogenic failure in XYSxra testes was predominantly between pachytene and diplotene, while in XOSxra testes the block was predominantly during the meiotic metaphases. To explain the spermatogenic anomalies in XYSxra and XOSxra testes, Burgoyne and Baker (1984) invoked the “meiotic pairing site” hypothesis of Miklos (1974). The other notable feature of the present study was the demonstration that the testicular deficiency is manifested earlier (with respect to age and spermatogenic stage) in XYSxra testes than in XOSxra testes. Krzanowska (1989) recently reported increased levels of X-Y univalence in pubertal XY males. So, it is suggested that this reduced efficiency of X-Y pairing at puberty that leads to the increased incidence of diploid spermatids in pubertal XYSxra males and to the presence of diploid spermatids in pubertal XY males. The other feature of pubertal XYSxra testes that deserves mention is the increase in the number of differentiating spermatogonia.

 

The conclusion is that most of the spermatogenic deficiencies in XYSxra and XOSxra testes can be explained in terms of the “meiotic pairing site” hypothesis, which links spermatogenic failure with sex chromosome univalence during meiosis. In XYSxra testes a variable proportion of pachytene spermatocytes have the X and Y unpaired, and the elimination of these cells explains the variable reduction in testis size and fertility. In XOSxra testes all spermatocytes have a univalent sex chromosome, accounting for the almost total spermatogenic block in these mice. It is suggested that the affected spermatocytes are eliminated earlier in XYSxra testes than in XOSxra testes, because two univalent sex chromosomes have more unpaired sites than the univalent X alone.

 

References:

 

Sutcliffe M. J., Darling S. M., Burgoyne P. S. (1991) Spermatogenesis in XY, XYSxra and XOSxra Mice: A quantitative analysis of spermatogenesis throughout puberty. Molecular Reprod. Dev. 30(2), 81–89.

 

Burgoyne P. S., Baker T. G. (1984) Meiotic pairing and gametogenic failure. In CW Evans and HG Dickinson (eds): “Controlling Events in Meiosis (38th Symp SOC Exp Biol).” Cambridge Company of Biologists, pp 349-362.

 

Miklos G. L. G. (1974) Sex-chromosome pairing and male fertility. Cytogen. Cell Genet. 13, 558-577.

 

Krzanowska H (1989) X-Y chromosome dissociation in mouse strains differing in efficiency of spermatogenesis: Elevated frequency of univalents in pubertal males. Gamete. Res. 23, 357-365.

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Lifelong Contraceptive Device for Men: Mechanical Switch to Control Fertility on Wish

Posted in Bio Instrumentation in Experimental Life Sciences Research, Bioengineering & reverse engineering design, BioTechnology - Venture Creation, Clinical & Translational, Medical Device Therapies for Altzheimer’s Disease, Methods, MicroEngineering Cell-Tissue & Systems, Personal Health Applications: Tech Innovations serves HealhCare, Reproductive Andrology, Embryology, Genomic Endocrinology, Preimplantation Genetic Diagnosis and Reproductive Genomics, Reproductive Biology & Bio Instrumentation, Social Development, Translational Research, tagged , , , , , , on January 14, 2016| Leave a Comment »

Lifelong Contraceptive Device for Men: Mechanical Switch to Control Fertility on Wish

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

There aren’t many options for long-term birth control for men. The most common kinds of male contraception include

  • condoms,
  • withdrawal / pulling out,
  • outercourse, and
  • vasectomy.

But, other than vasectomy none of the processes are fully secured, comfortable and user friendly. Another solution may be

  • RISUG (Reversible Inhibition of Sperm Under Guidance, or Vasalgel)

which is said to last for ten years and no birth control pill for men is available till date.

VIEW VIDEO

http://www.mdtmag.com/blog/2016/01/implanted-sperm-switch-turns-mens-fertility-and?et_cid=5050638&et_rid=461755519&type=cta

Recently a German inventor, Clemens Bimek, developed a novel, reversible, hormone free, uncomplicated and lifelong contraceptive device for controlling male fertility. His invention is named as Bimek SLV, which is basically a valve that stops the flow of sperm through the vas deferens with the literal flip of a mechanical switch inside the scortum, rendering its user temporarily sterile. Toggled through the skin of the scrotum, the device stays closed for three months to prevent accidental switching. Moreover, the switch can’t open on its own. The tiny valves are less than an inch long and weigh is less than a tenth of an ounce. They are surgically implanted on the vas deferens, the ducts which carry sperm from the testicles, through a simple half-hour operation.

The valves are made of PEEK OPTIMA, a medical-grade polymer that has long been employed as a material for implants. The device is patented back in 2000 and is scheduled to undergo clinical trials at the beginning of this year. The inventor claims that Bimek SLV’s efficacy is similar to that of vasectomy, it does not impact the ability to gain and maintain an erection and ejaculation will be normal devoid of the sperm cells. The valve’s design enables sperm to exit the side of the vas deferens when it’s closed without any semen blockage. Leaked sperm cells will be broken down by the immune system. The switch to stop sperm flow can be kept working for three months or 30 ejaculations. After switching on the sperm flow the inventor suggested consulting urologist to ensure that all the blocked sperms are cleared off the device. The recovery time after switching on the sperm flow is only one day, according to Bimek SLV. However, men are encouraged to wait one week before resuming sexual activities.

Before the patented technology can be brought to market, it must undergo a rigorous series of clinical trials. Bimek and his business partners are currently looking for men interested in testing the device. If the clinical trials are successful then this will be the first invention of its kind that gives men the ability to control their fertility and obviously this method will be preferred over vasectomy.

 

References:

 

https://www.bimek.com/this-is-how-the-bimek-slv-works/

 

http://www.mdtmag.com/blog/2016/01/implanted-sperm-switch-turns-mens-fertility-and?et_cid=5050638&et_rid=461755519&type=cta

 

http://www.telegraph.co.uk/news/worldnews/europe/germany/12083673/German-carpenter-invents-on-off-contraception-switch-for-sperm.html

 

http://www.discovery.com/dscovrd/tech/you-can-now-turn-off-your-sperm-flow-with-the-flip-of-a-switch/

 

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What Is Low Libido? Main Causes Of Low Libido In Men – Nutra Elite

Posted in Reproductive Andrology, Embryology, Genomic Endocrinology, Preimplantation Genetic Diagnosis and Reproductive Genomics on December 26, 2015| Leave a Comment »

What Is Low Libido? Main Causes Of Low Libido In Men – Nutra Elite

Reporter: Aviva Lev-Ari, PhD, RN

 

 

 

 

 

causes, libido, main, what What Is Low Libido? Main Causes Of Low Libido In Men Its 100% a myth that men want sex 24/7… Men suffer from low libido, or if you want to call it Low sex drive just as much as women.

Sourced through Scoop.it from: www.nutra-elite.com

See on Scoop.it – Cardiovascular Disease: PHARMACO-THERAPY

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How NGS Will Revolutionize Reproductive Diagnostics: November Meeting, Boston MA

Posted in Clinical Diagnostics, Clinical Genomics, Embryology, Endocrine Diseases, Genetics & Innovations in Treatment, Genomic Testing: Methodology for Diagnosis, Next Generation Sequencing (NGS), Reproductive Andrology, Embryology, Genomic Endocrinology, Preimplantation Genetic Diagnosis and Reproductive Genomics, Reproductive Biology & Bio Instrumentation, tagged , , , , , , , , , , , , , on September 10, 2015| Leave a Comment »

How NGS Will Revolutionize Reproductive Diagnostics: November Meeting, Boston MA, Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 1: Next Generation Sequencing (NGS)
Reproductive Genetic Dx | Nov. 18-19 | Boston, MA
Reporter: Stephen J. Williams, Ph.D.
Reproductive Genetic Diagnostics
Advances in Carrier Screening, Preimplantation Diagnostics, and POC Testing
November 18-19, 2015  |  Boston, MA
healthtech.com/reproductive-genetic-diagnosticsMount Sinai Hospital’s Dr. Tanmoy Mukherjee to Present at Reproductive Genetic Diagnostics ConferenceTanmoy MukherjeePodcastNumerical Chromosomal Abnormalities after PGS and D&C
Tanmoy Mukherjee, M.D., Assistant Clinical Professor, Obstetrics, Gynecology and Reproductive Science, Mount Sinai Hospital
This review provides an analysis of the most commonly identified numerical chromosome abnormalities following PGS and first trimester D&C samples in an infertile population utilizing ART. Although monosomies comprised >50% of all cytogenetic anomalies identified following PGS, there were very few identified in the post D&C samples. This suggests that while monosomies occur frequently in the IVF population, they commonly do not implant.

In a CHI podcast, Dr. Mukherjee discusses the current challenges facing reproductive specialists in regards to genetic diagnosis of recurrent pregnancy loss, as well as how NGS is affecting this type of testing > Listen to Podcast

Register  SAVE up to $200, Register by October 9

Learn More  |  Present a Poster  |  Sponsorship & Exhibit Information  |  View Brochure

CONFERENCE-AT-A-GLANCE

ADVANCES IN NGS AND OTHER TECHNOLOGIES

Keynote Presentation: Current and Expanding Invitations for Preimplantation Genetic Diagnosis (PGD)
Joe Leigh Simpson, MD, President for Research and Global Programs, March of Dimes Foundation

Next-Generation Sequencing: Its Role in Reproductive Medicine
Brynn Levy, Professor of Pathology & Cell Biology, CUMC; Director, Clinical Cytogenetics Laboratory, Co-Director, Division of Personalized Genomic Medicine, College of Physicians and Surgeons, Columbia University Medical Center, and the New York Presbyterian Hospital

CCS without WGA
Nathan Treff, Director, Molecular Biology Research, Reproductive Medicine Associates of New Jersey, Associate Professor, Department of Obstetrics, Gynecology, and Reproductive Sciences, Rutgers-Robert Wood Johnson Medical School, Adjunct Faculty Member, Department of Genetics, Rutgers-The State University of New Jersey

Concurrent PGD for Single Gene Disorders and Aneuploidy on a Single Trophectoderm Biopsy
Rebekah S. Zimmerman, Ph.D., FACMG, Director, Clinical Genetics, Foundation for Embryonic Competence

Live Birth of Two Healthy Babies with Monogenic Diseases and Chromosome Abnormality Simultaneously Avoided by MALBAC-based Combined PGD and PGS
Xiaoliang Sunney Xie, Ph.D., Mallinckrodt Professor of Chemistry and Chemical Biology, Department of Chemistry and Chemical Biology, Harvard University

Good Start GeneticsAnalytical Validation of a Novel NGS-Based Pre-implantation Genetic Screening Technology
Mark Umbarger, Ph.D., Director, Research and Development, Good Start Genetics


CLINICAL APPLICATIONS FOR ADVANCED TESTING TECHNOLOGIES

Expanded Carrier Screening for Monogenic Disorders
Peter Benn, Professor, Department of Genetics and Genome Sciences, University of Connecticut Health Center

Oocyte Mitochondrial Function and Testing: Implications for Assisted Reproduction
Emre Seli, MD, Yale School of Medicine

Preventing the Transmission of Mitochondrial Diseases through Germline Genome Editing
Alejandro Ocampo, Ph.D., Research Associate, Gene Expression Laboratory – Belmonte, Salk Institute for Biological Studies

Silicon BiosystemsRecovery and Analysis of Single (Fetal) Cells: DEPArray Based Strategy to Examine CPM and POC
Farideh Bischoff, Ph.D., Executive Director, Scientific Affairs, Silicon Biosystems, Inc.

> Sponsored Presentation (Opportunities Available)

Numerical Chromosomal Abnormalities after PGS and D&C
Tanmoy Mukherjee, M.D., Assistant Clinical Professor, Obstetrics, Gynecology and Reproductive Science, Mount Sinai Hospital

EMBRYO PREPARATION, ASSESSMENT, AND TREATMENT

Guidelines and Standards for Embryo Preparation: Embryo Culture, Growth and Biopsy Guidelines for Successful Genetic Diagnosis
Michael A. Lee, MS, TS, ELD (ABB), Director, Laboratories, Fertility Solutions

Current Status of Time-Lapse Imaging for Embryo Assessment and Selection in Clinical IVF
Catherine Racowsky, Professor, Department of Obstetrics, Gynecology & Reproductive Biology, Harvard Medical School; Director, IVF Laboratory, Brigham & Women’s Hospital

The Curious Case of Fresh versus Frozen Transfer
Denny Sakkas, Ph.D., Scientific Director, Boston IVF

Why Does IVF Fail? Finding a Single Euploid Embryo is Harder than You Think
Jamie Grifo, M.D., Ph.D., Program Director, New York University Fertility Center; Professor, New York University Langone Medical Center

BEST PRACTICES AND ETHICS

Genetic Counseling Bridges the Gap between Complex Genetic Information and Patient Care
MaryAnn W. Campion, Ed.D., MS, CGC; Director, Master’s Program in Genetic Counseling; Assistant Dean, Graduate Medical Sciences; Assistant Professor, Obstetrics and Gynecology, Boston University School of Medicine

Ethical Issues of Next-Generation Sequencing and Beyond
Eugene Pergament, M.D., Ph.D., FACMG, Professor, Obstetrics and Gynecology, Northwestern; Attending, Northwestern University Medical School Memorial Hospital

Closing Panel: The Future of Reproductive Genetic Diagnostics: Is Reproductive Technology Straining the Seams of Ethics?
Moderator:
Mache Seibel, M.D., Professor, OB/GYN, University of Massachusetts Medical School; Editor, My Menopause Magazine; Author, The Estrogen Window
Panelists:
Rebekah S. Zimmerman, Ph.D., FACMG, Director, Clinical Genetics, Foundation for Embryonic Competence
Denny Sakkas, Ph.D., Scientific Director, Boston IVF
Michael A. Lee, MS, TS, ELD (ABB), Director of Laboratories, Fertility Solutions
Nicholas Collins, MS, CGC, Manager, Reproductive Health Specialists, Counsyl

Arrive Early and Attend Advances in Prenatal Molecular Diagnostics – Register for Both Events and SAVE!
Prenatal Molecular Dx | Nov. 16-18 | Boston, MA

CHI, 250 First Avenue, Suite 300, Needham, MA, 02494, Tel: 781-972-5400 | Fax: 781-972-5425

 

 

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Fertilization: Protein Architecture of the Sperm’s Acrosomal Matrix, Filaments in Sperm Head Organelle Target the Egg

Posted in Reproductive Andrology, Embryology, Genomic Endocrinology, Preimplantation Genetic Diagnosis and Reproductive Genomics, Reproductive Biology & Bio Instrumentation on August 27, 2015| Leave a Comment »

Fertilization: Protein Architecture of the Sperm’s Acrosomal Matrix, Filaments in Sperm Head Organelle Target the Egg

Reporter: Aviva Lev-Ari, PhD, RN

 

Andrology. 2015 Jul;3(4):756-71. doi: 10.1111/andr.12057.

Sperm Lysozyme-Like Protein 1 (SLLP1), an intra-acrosomal oolemmal-binding sperm protein, reveals filamentous organization in protein crystal form.

Zheng H1, Mandal A2, Shumilin IA1, Chordia MD1, Panneerdoss S2, Herr JC2, Minor W1.

Author information

Abstract

Sperm lysozyme-like protein 1 (SLLP1) is one of the lysozyme-like proteins predominantly expressed in mammalian testes that lacks bacteriolytic activity, localizes in the sperm acrosome, and exhibits high affinity for an oolemmal receptor, SAS1B. The crystal structure of mouse SLLP1 (mSLLP1) was determined at 2.15 Å resolution. mSLLP1 monomer adopts a structural fold similar to that of chicken/mouse lysozymes retaining all four canonical disulfide bonds. mSLLP1 is distinct from c-lysozyme by substituting two essential catalytic residues (E35T/D52N), exhibiting different surface charge distribution, and by forming helical filaments approximately 75 Å in diameter with a 25 Å central pore comprised of six monomers per helix turn repeating every 33 Å. Cross-species alignment of all reported SLLP1 sequences revealed a set of invariant surface regions comprising a characteristic fingerprint uniquely identifying SLLP1 from other c-lysozyme family members. The fingerprint surface regions reside around the lips of the putative glycan-binding groove including three polar residues (Y33/E46/H113). A flexible salt bridge (E46-R61) was observed covering the glycan-binding groove. The conservation of these regions may be linked to their involvement in oolemmal protein binding. Interaction between SLLP1 monomer and its oolemmal receptor SAS1B was modeled using protein-protein docking algorithms, utilizing the SLLP1 fingerprint regions along with the SAS1B conserved surface regions. This computational model revealed complementarity between the conserved SLLP1/SAS1B interacting surfaces supporting the experimentally observed SLLP1/SAS1B interaction involved in fertilization.

© 2015 American Society of Andrology and European Academy of Andrology.

SOURCE

http://www.ncbi.nlm.nih.gov/pubmed?term=26198801

Fertilization Discovery: Do Sperm Carry Tiny Harpoons?

SLLP1-filament-side

Figure SOURCE
The SLLP1 filament viewed along the side with each neighboring monomer colored alternatively
Andrology. 2015 Jul;3(4):756-71. doi: 10.1111/andr.12057. Sperm Lysozyme-Like Protein 1 (SLLP1), an intra-acrosomal oolemmal-binding sperm protein, reveals filamentous organization in protein crystal form.

AUGUST 26, 2015
JOSH BARNEY

Could the sperm harpoon the egg to facilitate fertilization? That’s the intriguing possibility raised by the University of Virginia School of Medicine’s discovery that a protein within the head of the sperm forms spiky filaments, suggesting that these tiny filaments may lash together the sperm and its target.

The finding, 14 years in the making, has earned the cover of the scientific journal Andrology. It represents a significant step forward in the fine dissection of the protein architecture of the sperm’s acrosomal matrix, an organelle in the sperm head, and suggests a new hypothesis concerning what happens during fertilization.

“This finding has really captured our imagination,” said U.Va. reproduction researcher John Herr of the Department of Cell Biology. “One of the major proteins that is abundant in the acrosome [in the anterior region of the sperm head] is crystallizing into filaments, and we now postulate they’re involved in penetrating the egg ­– that’s the new hypothesis emerging from the finding, which leads to a whole new set of questions and new hypotheses about the very fine structure of molecular events during fertilization.”

The discovery is the result of a longstanding collaboration between Herr’s lab and the lab of Wladek Minor of the Department of Molecular Physiology and Biological Physics. Years ago, Herr’s lab discovered the protein that has now been shown to form the filaments, which they dubbed sperm lysozyme-like protein 1, or SLLP1. This protein is a member of a family of proteins now known to reside inside the acrosome.

Herr’s lab, however, had no way to determine the shape and structure of the protein. That’s where Minor’s lab came in. To figure it out, Minor’s team had to capture the protein within a static crystal, cool the crystal to cryogenic temperatures to prevent decay and then blast it with X-rays. By examining how those X-rays were refracted, they could calculate the shape of the protein, somewhat like mapping out a shipwreck with sonar.

It was no easy task, requiring many attempts and much analysis. But in the end, they were able to produce one of the first descriptions of a sperm protein.

“This is an important protein, because it’s the first crystal structure from a protein within the sperm acrosome,” said Heping Zheng, the lead author of the paper outlining the discovery. “It is also the first structure of a mammalian sperm protein with a specific oocyte-side binding partner characterized. To our knowledge, only nine proteins specifically obtained from mammalian sperm have known structures.”

The new understanding of the structure will now act as a map for Herr and other reproductive biologists exploring how fertilization occurs. “At the very fundamental level, understanding that fine molecular architecture leads me, the biologist, to be able to posit new functions for this family of proteins my lab discovered in the acrosome,” Herr explained.

The mutually beneficial collaboration between the labs is vital, Minor noted. “You have to explain the relation between structure and function,” he said. “You can make a beautiful picture of the Himalayas, for example. For some time, when nobody knew the Himalayas, it was enough to show the picture. It was a beautiful picture; nobody had seen that before. Now, you can go close to Mount Everest, you can make a picture, you can send it to the Washington Post or the New York Times. Nobody will print that, because who cares? They have millions of these pictures. But if you have a story about someone who climbed the mountain in winter, skied down and saved the life of another climber, you have a story for the front page of the New York Times. It’s the same here. You must have a story, a novel understanding, to go with the structure on the cover of the journal.”

The structure has been detailed in an article published in Andrology by Heping Zheng, Arabinda Mandal, Igor A. Shumilin, Mahendra D. Chordia, Subbarayalu Panneerdoss, John Herr and Wladek Minor.

About the Author

Josh Barney

U.Va. Health System
434-243-1988

Media Contact:

Josh Barney

U.Va. Health System

434-243-1988

SOURCE

http://news.virginia.edu/content/fertilization-discovery-do-sperm-carry-tiny-harpoons

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Sexual Desire Disorder in Pre-menopausal Women: Addyi (flibanserin) is intended to increase libido – ‘Female Viagra’ approved by FDA

Posted in Endocrine Diseases, FDA, FDA Regulatory Affairs, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, Reproductive Andrology, Embryology, Genomic Endocrinology, Preimplantation Genetic Diagnosis and Reproductive Genomics, Reproductive Biology & Bio Instrumentation on August 18, 2015| Leave a Comment »

Sexual Desire Disorder in Pre-menopausal Women: Addyi (flibanserin) is intended to increase libido – ‘Female Viagra’ approved by FDA

Reporter: Aviva Lev-Ari, PhD

FDA News Release

FDA approves first treatment for sexual desire disorder

For Immediate Release

August 18, 2015

Release

Español

The U.S. Food and Drug Administration today approved Addyi (flibanserin) to treat acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. Prior to Addyi’s approval, there were no FDA-approved treatments for sexual desire disorders in men or women.

“Today’s approval provides women distressed by their low sexual desire with an approved treatment option,” said Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research (CDER). “The FDA strives to protect and advance the health of women, and we are committed to supporting the development of safe and effective treatments for female sexual dysfunction.”

HSDD is characterized by low sexual desire that causes marked distress or interpersonal difficulty and is not due to a co-existing medical or psychiatric condition, problems within the relationship, or the effects of a medication or other drug substance. HSDD is acquired when it develops in a patient who previously had no problems with sexual desire. HSDD is generalized when it occurs regardless of the type of sexual activity, the situation or the sexual partner.

“Because of a potentially serious interaction with alcohol, treatment with Addyi will only be available through certified health care professionals and certified pharmacies,” continued Dr. Woodcock. “Patients and prescribers should fully understand the risks associated with the use of Addyi before considering treatment.”

Addyi can cause severely low blood pressure (hypotension) and loss of consciousness (syncope). These risks are increased and more severe when patients drink alcohol or take Addyi with certain medicines (known as moderate or strong CYP3A4 inhibitors) that interfere with the breakdown of Addyi in the body. Because of the alcohol interaction, the use of alcohol is contraindicated while taking Addyi. Health care professionals must assess the likelihood of the patient reliably abstaining from alcohol before prescribing Addyi.

Addyi is being approved with a risk evaluation and mitigation strategy (REMS), which includes elements to assure safe use (ETASU). The FDA is requiring this REMS because of the increased risk of severe hypotension and syncope due to the interaction between Addyi and alcohol. The REMS requires that prescribers be certified with the REMS program by enrolling and completing training. Certified prescribers must counsel patients using a Patient-Provider Agreement Form about the increased risk of severe hypotension and syncope and about the importance of not drinking alcohol during treatment with Addyi. Additionally, pharmacies must be certified with the REMS program by enrolling and completing training. Certified pharmacies must only dispense Addyi to patients with a prescription from a certified prescriber. Additionally, pharmacists must counsel patients prior to dispensing not to drink alcohol during treatment with Addyi.

Addyi is also being approved with a Boxed Warning to highlight the risks of severe hypotension and syncope in patients who drink alcohol during treatment with Addyi, in those who also use moderate or strong CYP3A4 inhibitors, and in those who have liver impairment. Addyi is contraindicated in these patients. In addition, the FDA is requiring the company that owns Addyi to conduct three well-designed studies in women to better understand the known serious risks of the interaction between Addyi and alcohol.

Addyi is a serotonin 1A receptor agonist and a serotonin 2A receptor antagonist, but the mechanism by which the drug improves sexual desire and related distress is not known. Addyi is taken once daily. It is dosed at bedtime to help decrease the risk of adverse events occurring due to possible hypotension, syncope and central nervous system depression (such as sleepiness and sedation). Patients should discontinue treatment after eight weeks if they do not report an improvement in sexual desire and associated distress.

The effectiveness of the 100 mg bedtime dose of Addyi was evaluated in three 24-week randomized, double-blind, placebo-controlled trials in about 2,400 premenopausal women with acquired, generalized HSDD. The average age of the trial participants was 36 years, with an average duration of HSDD of approximately five years. In these trials, women counted the number of satisfying sexual events, reported sexual desire over the preceding four weeks (scored on a range of 1.2 to 6.0) and reported distress related to low sexual desire (on a range of 0 to 4). On average, treatment with Addyi increased the number of satisfying sexual events by 0.5 to one additional event per month over placebo increased the sexual desire score by 0.3 to 0.4 over placebo, and decreased the distress score related to sexual desire by 0.3 to 0.4 over placebo. Additional analyses explored whether the improvements with Addyi were meaningful to patients, taking into account the effects of treatment seen among those patients who reported feeling much improved or very much improved overall. Across the three trials, about 10 percent more Addyi-treated patients than placebo-treated patients reported meaningful improvements in satisfying sexual events, sexual desire or distress. Addyi has not been shown to enhance sexual performance.

The 100 mg bedtime dose of Addyi has been administered to about 3,000 generally healthy premenopausal women with acquired, generalized HSDD in clinical trials, of whom about 1,700 received treatment for at least six months and 850 received treatment for at least one year.

The most common adverse reactions associated with the use of Addyi are dizziness, somnolence (sleepiness), nausea, fatigue, insomnia and dry mouth.

The FDA has recognized for some time the challenges involved in developing treatments for female sexual dysfunction. The FDA held a public Patient-Focused Drug Development meeting and scientific workshop on female sexual dysfunction on October 27 and October 28, 2014, to solicit perspectives directly from patients about their condition and its impact on daily life, and to discuss the scientific challenges related to developing drugs to treat these disorders. The FDA continues to encourage drug development in this area.

Consumers and health care professionals are encouraged to report adverse reactions from the use of Addyi to the FDA’s MedWatch Adverse Event Reporting program at www.fda.gov/MedWatch or by calling 1-800-FDA-1088.

Addyi is marketed by Sprout Pharmaceuticals, based in Raleigh, North Carolina.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

SOURCE

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm458734.htm

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Metabolic Genomics and Pharmaceutics, Vol. 1 of BioMed Series D available on Amazon Kindle

Posted in Academic Publishing, Amino acids, Anaerobic Glycolysis, Biochemical pathways, Biological Networks, Biomarkers & Medical Diagnostics, Bone Disease and Musculoskeletal Disease, Ca2+ triggered activation, Cachexia, Calcium, Calcium Signaling, Calmodulin, Calmodulin Kinase and Contraction, Cancer and Current Therapeutics, CANCER BIOLOGY & Innovations in Cancer Therapy, Cancer Informatics, Cardiac & Vascular Repair Tools Subsegment, Cardiac and Cardiovascular Surgical Procedures, Cardiac muscle regeneration, Cardiomyopathy, Cardiovascular Pharmacogenomics, Cardiovascular Research, Cell Biology, Chemical Biology and its relations to Metabolic Disease, Clinical & Translational, Clinical Diagnostics, Clinical Genomics, Competition in regenerative stem cell science, Curation, Curation methodology, Cytoskeleton, Dehydrogenase, Diabetes Mellitus, Discovery process, Disease Biology, Endocrine Diseases, Enzyme Induction, Enzymes and isoenzymes, Explanatory, Fatty acids, Folate and B12, Frontiers in Cardiology and Cardiovascular Disorders, Gene Regulation, Gene Regulation and Evolution, Genome Biology, Genomic Endocrinology, Genomic Expression, Glycobiology: Biopharmaceutical Production, Health Economics and Outcomes Research, Hexokinase, Historical relevance, Inosine nucleotides, Interviews with Scientific Leaders, Iron deficiency, Kinase, Lipid metabolism, Lipids, Liver & Digestive Diseases Research, Loss of function gene, Metabolism, Metabolomics, Methylation, Mg++, Molecular Genetics & Pharmaceutical, mtDNA, Mutant Gene Expression, Myelodysplasia, Myelofibrosis, Myocardial Ischemia, Myocardial Metabolism, Na-K-ATPase, Neurodegenerative Diseases, Neurohumoral Transmission, Nitric Oxide in Health and Disease, Nutrigenomics, Nutrition, Nutrition and Phytochemistry, Nutrition Disorders, Nutritional Supplements: Atherogenesis, Open Access Journals, Oxidative phosphorylation, Pentose monophosphate shunt, Phosphatase, Phosphorylase, Phosphorylation, PKC, Plant extract, Proteins, Proteomics, Pyridine nucleotide transhydrogenase, Pyridine nucleotides, Pyruvate Kinase, Reproductive Andrology, Embryology, Genomic Endocrinology, Preimplantation Genetic Diagnosis and Reproductive Genomics, RNA Biology, S-nitrosylation, Signaling, Signaling & Cell Circuits, Skeletal muscle regeneration, Small Molecules in Development of Therapeutic Drugs, Theoretic convergence, Transcriptomics, Translational Science, Ubiquitinylation, Warburg effect, tagged , , , , , , , , , , , , , , , , , on August 15, 2015| Leave a Comment »

Metabolic Genomics and Pharmaceutics, Vol. 1 of BioMed Series D available on Amazon Kindle

Reporter: Stephen S Williams, PhD

Article ID #180: Metabolic Genomics and Pharmaceutics, Vol. 1 of BioMed Series D available on Amazon Kindle. Published on 8/15/2015

WordCloud Image Produced by Adam Tubman

Leaders in Pharmaceutical Business Intelligence would like to announce the First volume of their BioMedical E-Book Series D:

Metabolic Genomics & Pharmaceutics, Vol. I

SACHS FLYER 2014 Metabolomics SeriesDindividualred-page2

which is now available on Amazon Kindle at

http://www.amazon.com/dp/B012BB0ZF0.

This e-Book is a comprehensive review of recent Original Research on  METABOLOMICS and related opportunities for Targeted Therapy written by Experts, Authors, Writers. This is the first volume of the Series D: e-Books on BioMedicine – Metabolomics, Immunology, Infectious Diseases.  It is written for comprehension at the third year medical student level, or as a reference for licensing board exams, but it is also written for the education of a first time baccalaureate degree reader in the biological sciences.  Hopefully, it can be read with great interest by the undergraduate student who is undecided in the choice of a career. The results of Original Research are gaining value added for the e-Reader by the Methodology of Curation. The e-Book’s articles have been published on the Open Access Online Scientific Journal, since April 2012.  All new articles on this subject, will continue to be incorporated, as published with periodical updates.

We invite e-Readers to write an Article Reviews on Amazon for this e-Book on Amazon.

All forthcoming BioMed e-Book Titles can be viewed at:

http://pharmaceuticalintelligence.com/biomed-e-books/

Leaders in Pharmaceutical Business Intelligence, launched in April 2012 an Open Access Online Scientific Journal is a scientific, medical and business multi expert authoring environment in several domains of  life sciences, pharmaceutical, healthcare & medicine industries. The venture operates as an online scientific intellectual exchange at their website http://pharmaceuticalintelligence.com and for curation and reporting on frontiers in biomedical, biological sciences, healthcare economics, pharmacology, pharmaceuticals & medicine. In addition the venture publishes a Medical E-book Series available on Amazon’s Kindle platform.

Analyzing and sharing the vast and rapidly expanding volume of scientific knowledge has never been so crucial to innovation in the medical field. WE are addressing need of overcoming this scientific information overload by:

  • delivering curation and summary interpretations of latest findings and innovations on an open-access, Web 2.0 platform with future goals of providing primarily concept-driven search in the near future
  • providing a social platform for scientists and clinicians to enter into discussion using social media
  • compiling recent discoveries and issues in yearly-updated Medical E-book Series on Amazon’s mobile Kindle platform

This curation offers better organization and visibility to the critical information useful for the next innovations in academic, clinical, and industrial research by providing these hybrid networks.

Table of Contents for Metabolic Genomics & Pharmaceutics, Vol. I

Chapter 1: Metabolic Pathways

Chapter 2: Lipid Metabolism

Chapter 3: Cell Signaling

Chapter 4: Protein Synthesis and Degradation

Chapter 5: Sub-cellular Structure

Chapter 6: Proteomics

Chapter 7: Metabolomics

Chapter 8:  Impairments in Pathological States: Endocrine Disorders; Stress

                   Hypermetabolism and Cancer

Chapter 9: Genomic Expression in Health and Disease 

 

Summary 

Epilogue

 

 

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