Birth Control Pill for Men

To date the only options men have for contraception are condoms or vasectomy. Studies have shown that many men would theoretically take a birth control  pill if it were available to them. However, research into male reproduction has traditionally been geared towards treatment to reverse infertility not to induce it. Comparatively little effort has been spent on developing a male contraceptive analogous to the female birth control pill. Of the work that has been done, most of it has been on researching and developing hormonal methods of male contraception. Similar to the “pill”, which uses hormones to block ovulation in women, hormonal male contraceptives block the development of spermatozoa by inhibiting spermatogenesis; inducing a state of azoospermia.

Azoopermia is the absence of spermatozoa in the semen of adult males. Hormonal male contraception focuses mainly around modulating testosterone levels to produce the desired effect of diminished fertility in men. However, like their female counterpart, the use of hormonal methods have undesirable side effects that can negatively impact ones health. As a result, non-hormonal methods have been investigated, to develop safer and more practical contraceptives for men. Non-hormonal contraceptives are designed to directly impact either the development, motility, or capacity of spermatozoa.

One promising non-hormonal strategy that has been investigated is, immunocontraception, which is the use of immunization to temporarily and reversibly inhibit male fertility. Early studies into male fertility found that infertile men often had anti-sperm antibodies. Antibodies are proteins produces by immune cells in the body against pathogens like bacteria and viruses. This lead researches to postulate that sperm specific proteins found in the testis could be used for the development of a contraceptive for men. One protein, in particular, known as Eppin, has be shown to be a promising target for the development of a non-hormonal male contraceptive.

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 Eppin

Eppin or Epididymal Protease Inhibitor, is a protein specific to the male reproductive system. Expressed in the testis and epididymis,  it is found on the surface of sperm and is essential for male fertility.  It forms a complex with another protein, known as Semenogelin, which is secreted by the seminal vesicles as the major component of seminal plasma coagulum.. Together they are essential for the proper function of ejaculated spermatozoa.

Eppin Targeted for the Development of Male Contraceptive

To study whether Eppin could successfully be used as an immunocontraceptive, scientist at the Indian Institute of Science conducted research to determine the effect of the immune response elicited by immunization with Eppin on spermatozoa. They tested whether antibodies to Eppin would cause infertility.

Adult male M. Radiate monkeys were immunized with human recombinant Eppin. Then  their ability to impregnate several female monkeys was tested. Monkeys with a high antibody tither were unable to impregnate any  females, and were therefore deemed infertile. Monkey’s that were not able to obtain a high antibody tither were excluded from the study. Over a year after immunization, 71% of the monkeys regained fertility. This showed that Eppin is essential to male fertility in humans and primates. In addition, immunization did not interfere with spermatogenesis (as is the case with hormonal methods). Neither testosterone levels nor sperm count were altered. Although safe and efficacious, anti-Eppin immunization was problematic mainly because infertility was not reversible in all subjects. In addition to irreversible infertility in some subjects receiving anti-Eppin, the antibody may elicit an adverse autoimmune responses, causing inflammation and infection, culminating in permanent infertility`. Antibodies are also degraded in the stomach, which would require that the method be delivered via injection.

At the time, the mechanism of action of many spermatozoa surface proteins like Eppin were just being studied, and the interplay of Eppin with Semenogelin and their role in sperm motility was not yet fully understood.  It  was determined that Eppins association with Semenogelin inhibited sperm motility. However, researchers observed that the infertile immunized monkeys lacked semen coagulum.  The antibodies against Eppin, blocked Semenogelin from binding to Eppin on the surface of spermatozoa. Instead the anti-Eppin antibodies would bind Eppin in place of Semenogelin, thereby also  retarding sperm motility. This showed that Semenogelin was also essential to male fertility.

The inhibition of sperm motility by the Eppin-Semenogelin complex differ from that of an Anti-Eppin-Eppin complex. One being necessary for fertility and the other inducing infertility. Figuring out the role that the Eppin-Semenogelin complex played in male fertility would be key to figuring out how induce infertility for the purpose of contraception.

Eppin Physiological Function

It was later understood that Eppin functions as a protective shield, guarding spermatozoa against bacterial and proteolytic attack while in the female reproductive tract. Prior to ejaculation spermatozoa travel through the ducts of the male reproductive system where they are mixed with secretions from the seminal vesicles and prostate gland. During this process Eppin binds other proteins at the surface of sperm, such as Semenogelin.  Semenogelin stops sperm from swimming, and is responsible for the gelatinous nature of the initial ejaculate. By the binding of Eppin and Semenogelen. sperm are kept in an immotile state which prevents their hyperactivation (before reaching their target).

In order for sperm to be capacitated, the seminal coagulum needs to undergo liquefaction. This process takes from five to 30 minutes, and involves the cleavage of Semenogelin by a protease called, Prostate Specific Antigen (PSA), from the Eppin-Semenogelin complex.  Eppin inhibits the displacement of Semenogelin by PSA, and since Eppin itself is not hydrolyzed by PSA, it modulates the gradual removal of Senemogelin from the surface of spermatozoa, enabling the progressive release of motile sperm. The removal of the Eppin-Semenogelin complex is necessary for fertility, failure to remove this complex results in impaired spermatozoa. Essentially the complex incapacitates spermatozoa, and its removal allows for gradual hyperactivation of the cell, allowing it to migrate up through the female reproductive tract. Without its formation sperm expend their energy immaturely.

Eppin: Immunocontraceptive to Small Molecule Drugs

In 2016, researchers at the University of North Carolina at Chapel Hill (UNC) submitted a patent application for a non-hormonal male contraceptive. The premise for their application, that small molecules that mimic Eppin can be used to inhibit male fertility, is based on the previous immunocontraceptive study in monkeys from 2004.

To overcome the shortcomings of immunocontraception, UNC researchers developed a series of small organic molecules that act like anti-Eppin antibodies, and prevent sperm motility. Because these compounds occupy the same sites,  they block  Anti-Eppin antibodies and Semenegelin from binding to Eppin. Binding to Eppin by either of these substances triggers a drop in pH level within spermatozoa, which subsequently decreases intracellular calcium levels, through the prevention of extracellular calcium uptake. This prevents the formation of contractile force energy needed for motion. For normal physiological function the pH level within sperm needs to increase in order to facilitate hyperactivation, which takes place after ejaculation with the gradual enzymatic removal of Semenogelin by PSA from the Semenogelin-Eppin complex.  Unlike with semenogelin and PSA, there is no gradual enzymatic removal of Anti-Eppin Antibodies or these small molecules from Eppin binding sites after ejaculation.

Since there is no semenogelin binding, there is no seminal coagulum formed. Therefore, sperm motility is inhibited not by the physical encapsulation of sperm within coagulum, but by the reaction that takes place when Eppin binding sites are occupied.

Using small molecule drugs to impair male fertility is advantageous to current male contraceptive options, as their action is safe, efficacious, and reversible. Condoms may fail due to user error, hormonal contraceptives and immunocontraceptives vary in efficacy by the individual and may produce unwanted side effects, and like vasectomies, they are not readily reversible.

Small molecule targeting Eppin represent a new class of therapeutic agents that specifically target spermatozoa without disrupting spermatogenesis or altering hormone levels. They can be used administered orally to inhibit sperm motility prior to ejaculation, or applied topically after ejaculation, to directly inhibit motility on contact with spermatozoa. Therefore, these  compounds can be used as a sole means of contraception or when applied topically, in conjunction with condoms, diaphragms, and spermicidal jellies.

Reference

  1. The University of North Carolina at Chapel Hill Applies for Patent on Small Molecules for Inhibiting Male Fertility. (2017, Mar 04). Global IP News.Pharmaceutical .
  2. John K Amory, 2016. Male Contraception. Fertility and Sterility Vol 106:6 p 1303-1309.
  3. O’Rand Michael G., Silva Erick J.R., Hamil G. Katherine, 2016. Non-hormonal male contraception: A review and development of an Eppin based contraceptive. Pharmacology & Therapeutics Vol 157 p105-111.

  4. Silva, Erick J.R., Hamil Katherine G., O’Rand Michael G., 2013. Interacting Proteins on Human Spermatozoa: Adaptive Evolution of the Binding of Semenogelin I to EPPIN. PLoS One 8:12 e82014.

  5. O’Rand, ,M.G., Widgren, E. E., Sivashanmugam, P., Richardson, R. T., & al, e. (2004). Reversible immunocontraception in male monkeys immunized with eppin. Science, 306(5699), 1189-90.

 

Cocaine Enhanced HIV/AIDS

Drug use is the second leading cause of acquiring HIV (Human Immunodeficiency Virus). It is well-known, that using illicit drugs such as marijuana, opiates, amphetamines, and cocaine, increases susceptibility to becoming infected with HIV due to high risk behavior associated with drug use, such as, unprotected sex, particularly in exchange for drugs or money, and non compliance to anti-retroviral treatment. However, the likelihood of acquiring HIV/AIDS is increased by cocaine use in both heterosexual and homosexual women and men, regardless of intravenous (IV) drug use. Even when compared to IV drug users of other drugs, such as opiates, the incidence of HIV is greater in cocaine addicts. This indicates that increased susceptibility to HIV can’t be explained by this factor alone. Additionally, there is an association between cocaine abuse and rapid conversion of HIV infections to AIDS.

Cofactor in HIV pathogenesis

Chimera mice were used to investigate the effect of cocaine on HIV pathogenicity. Specially breed mice, humanized to express a functional human immune system, were infected with HIV in the presence or absence of cocaine. Cocaine co-exposure led to the acceleration of HIV infection, a decrease in CD4+ cells, and a significant spike in circulating viral load. (Hybrid human-mouse model was used because normal mouse cells do not become infected with HIV, and exposing human test subjects to HIV and cocaine would be unethical and illegal). Continue reading

Macrophage, Liposomes, & Tattoo Removal

Many people get tattoos that for one reason or the other, they no longer desire to have. The only current option to erase permanent tattoos is laser tattoo removal. The process of removing tattoos by laser therapy is long, painful, expensive, and in about 5% of cases complications can arise.  However,  a faster, easier, and cheaper method of tattoo removal may soon be on the market.  Most recently, a scientist by the name of Alec Falkenham came up with the idea for an investigational tattoo removal cream, when he was a pathology PhD student at Dalhousie University in Halifax, Nova Scotia. As of 2016, the cream is being developed by Cipher Pharmaceuticals Inc. for commercial use.

Tattoo Removal Cream

Bisphosphonate Liposomal Tattoo Removal is a topical cream intended to remove or reduce the appearance of tattoos. It is designed to be used alone or as an adjuvant to hasten the process of laser tattoo removal.  It is proposed that the cream would require once a week application, and remove the tattoo in as little as a couple of months. Continue reading

Cellular Agriculture: Vegans Dream or Meat-eaters Nightmare?

The day is coming when there will be a more efficient supply chain for the production of meat and meat by-products. A new field of science known as Cellular Agriculture is using bioengineering technology to produce meat, poultry, eggs, dairy, and leather, in a laboratory instead of on a farm. You could drink cow’s milk, and eat eggs, meat, and poultry without the unwanted saturated fats, cholesterol, hormones, and antibiotics. Tissue engineering is even being employed in biofabrication of leather and fur, negating moral issues of raising animals for clothing and luxury. All of this without the use or slaughter of  animals.

What is Cellular Agriculture? 

Cellular agriculture is a new way to cultivate foods normally produced through traditional agriculture. Instead of raising livestock for meat, dairy, and other meat by-products, these items are produced in a lab, without the slaughter and continuous use of animals. Foods like eggs, milk, and beef can be bioengineered ex-vivo – using cell culture methods. Cellular agriculture can produce both cellular and acellular products. Cellular products, like beef, chicken, and turkey, are made by culturing cells derived from the original animal. Acellular products on the other hand do not contain any mammalian cells, and are derived from bioengineered microbes. Continue reading

“On The Spot” with Lani – Ph.D. Grad Student.

Graduate school can be tough, but being a graduate student in the STEM can be exceptionally challenging. The challenges are not just academic, but social, and personal. In my experience being a graduate student is somewhat of a mystery to many people. To illustrate what its like to pursue a Ph.D in science, I’ve interviewed another Doctoral Candidate, from Auburn University, Alabama. She responded in pink font, and I felt it was so indicative of her personality, that I kept it. I enjoyed reading about her journey. Keep reading to find out how a one time aspiring model becomes a scientist.

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Allergic to Penicillin? Maybe Not.

Most people can recall being asked by the doctor whether they have an allergy to penicillin or not. In fact, 10 percent of the general population is estimated to have Penicillin Allergy. However, in the past few years, the prevalence of Penicillin Allergy has decreased.

Studies have found that when tested, the vast majority of people who reported having Penicillin Allergy, are not allergic to the drug. Clinicians found, that many people who were told they were allergic to penicillin, never had their allergy confirmed with testing. Interestingly, others who were positively diagnosed in the past, were no longer allergic to penicillin.  Continue reading

Ebola Vaccine

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I recently wrote another article for Bioislifemedia.com about an Ebola Vaccine. Before you read it, first learn about Ebola by reading this article that I published last year What Ever Happened to Ebola?!

“Ebola is a virus in the family of Filoviridae along with Marbug virus, that causes Hemorrhagic Fever. The virus leads to hemorrhaging by causing the body to lose the ability for your blood to clot, through multiorgan damage and drop in blood pressure. There are actually several Ebola viruses: Sudan Ebola, Zaire Ebola, Cote D’Ivoire Ebola, and Bundibugyo Ebola. They are all distinct species of Ebolavirus. The virus got it’s name from a small river in northwestern Democratic Republic of the Congo (DRC). – Stacia Nicholson, What Ever Happened to Ebola?!

Then read about the candidate drug that may be the first vaccine to prevent Ebola in humans.

 

Science Writer

15698247_10102718125616547_9037553185852513701_nI have joined forces with BioisLifeMedia.com, a new website designed ” to bring trustworthy, clear, and noteworthy biomedical science & scientific content to the public”. The concept is dear to me as It mirrors my own mission; to present science in a practical manner, in which to give the public the information they need to truly understand current issues in science.

Bio is Life Media was founded in fall 2016 by Scientists,  Lebaron Agostini and David Deming II, and Advertising Account Manager, Nate Valazquez. The interactive site does not use sensationalism and dramatised conclusions to bait the public. Bio is Life Media works to promote an interest in science by sharing the perspectives of scientists, graduates students, medical professionals, entrepreneurs, and tech innovators. This is accomplished by creating quality content that bridges the gap between the scientists/scientific information, the media, and the general public, so that society can make better informed decisions.

Two years ago when I started Aliquot the Science Spot, it was my vision, that a community of responsible scientists and medical professionals would network to change the face of science journalism as we know it. I am ecstatic to see that dream actualizing, and to be able to collaborate with other researchers who share the same vision and passion as I do.

I have signed on as a Contributor for Bio Is Life Media, and my first article with the site has recently been published. Read the article I wrote, entitled Monkey AIDS and Man.

 

Varicella Disease: Chickenpox & Shingles

Varicella was once a common childhood disease. Due to childhood vaccination initiated in 1996 in the United States, the viral infection has already begun to fade out of common knowledge. Many young adults and adolescents today, have never experienced the itchy blistering rash, or missed days of school because of it. Some people have even begun to contest the necessity of vaccinating against the virus that causes chickenpox infections in children. However, preventing chickenpox can also prevent two painfully debilitating conditions later on in life; Shingles and Postherpetic Neuralgia.

Varicella-Zoster Virus

The Varunknownicella-Zoster Virus (VZV) is a DNA herpesvirus that infects humans and some primates.  It is the cause of both Chickenpox (Varicella disease) and Shingles (Herpes Zoster).

Varicella Disease: Chickenpox

Chickenpox is a highly infectious childhood disease that primarily affects children between the ages of 1 and 9 years old. It causes an itchy vesicular rash to appear on the body, accompanied by fever and malaise.

Chickenpox is self-limiting, and does not require treatment to be resolved. Healthy individuals develop a mild disease that  generally clears within a few weeks. Symptoms such as dehydration, fever, and puritis, can be managed with fluid replacement, acetaminophen, and calamine lotion, respectively. Continue reading

Phony Pharmaceuticals, Counterfeit Medicine as Dangerous as Street Drugs.

Fraudulent pharmacies have popped up all over the internet, to take advantage of the high profits that can be made off of selling pharmaceutical drugs. These sites often offer cheap prices and discounts on otherwise expensive medications. They also usually allow the purchase of prescription medicines without the need for a prescription. Often-times the medicines sold online are counterfeit medicines, and while they may seem like a suitable alternative to expensive prescription drugs, they are harmful. The manufacture, warehousing, distribution, and sale of counterfeit drugs is a criminal enterprise, and worldwide problem affecting the healthcare system. Globally, the counterfeit pharmaceutical drug trade is a multibillion dollar industry, and ten percent of the worlds medicines are counterfeit.

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