American Society of Andrology.

NEWSLETTER, VOLUME 2

Message from the ASA President

Dear Colleagues,

We live in challenging times for research in general and even more in the field of reproduction. Indeed, reproductive biology and andrology are not “hot” research areas and our politicians, funders and society are wondering whether research in reproduction is still needed. Thankfully the recent advents of testosterone-replacement therapy, progress in the biology of male germ stem cells and the sensitivity of male reproductive system to environmental exposures have proven that there is still a lot to learn and that advances in the field have direct impact in human health, disease and the maintenance of the species.

Reduced federal and industry funding, increased demand for funding, changing technologies requiring larger investments and expensive publication venues have brought up many research labs to financial difficulties.  In addition, the proliferation of many specialized meetings, the overlap of the mission of various societies and the fact that most society journals are viewed as second tier “specialized” journals in the eyes of grant reviewers and the scientific community in general have resulted in limited interest of young, and even some senior, investigators to be part of small societies and publish in society journals.  The result of all these changes is that we have to make hard decisions on choosing carefully our field of research, membership in societies and attendance to meetings.

Because ASA is a small and specialized society, ASA Council has many times pondered on the question on what to do to become an attractive place for young investigators to join and for our senior membership to continue their membership.  Having a high quality exciting and inspiring scientific meeting is one of the answers to the question. Our Program Chairs, Program Committee and Council have spent a lot of time ensuring that what will be presented at the annual ASA meeting is timely, new, of high caliber and interest to both fundamental and clinical andrologists.  Moreover, there is an ongoing effort to engage our trainees, expand on round-table discussions and networking as well as recognize our best and most committed members.

Today the field of Andrology is dealing with numerous current and important issues, ranging from molecules to society.  Our goals (duty) are to keep at the forefront of science and educate tomorrow's scientists and clinicians, along with governments/funding agencies, on the relevance of Andrology for health and society, in order to regain their full attention and support.

Please join me at the 41st Annual Meeting of the ASA, entitled “Old Dogmas, New Ideas: The Changing Landscape in Andrology” that will be held at the Astor Crowne Plaza in New Orleans, Louisiana, April 2 –A 5, 2016.

Let’s start together the next 40 years of ASA with a memorable meeting in New Orleans.

I look forward to seeing you there.

Vassilios Papadopoulos, DPharm, PhD
President, American Society of Andrology

Why get involved with ASA?

I joined the ASA as a trainee member in 1999, the year I attended my first ASA meeting. At the meeting I was awarded the ASA Outstanding Trainee Investigator Award, which was a tremendous honor.

I am currently a regular member of the Society. Many of my trainees have also become ASA trainee members and have received Trainee Merit Awards over the past few years—this is something that I am very proud of. Some of my former trainees have established their own labs and are still ASA members, as are their trainees. I like to think of this as my small ASA family tree!

The ASA was instrumental for my professional development. By being a member of the ASA, I have had the privilege to meet great andrologists and to develop scientific collaborations with many of them.

The opportunity to meet people from different institutions from all over the world and at different career stages is a wonderful way of expanding your professional network, while making new friends along the way! There are several ways one can get involved in the society, including paying your dues and attending the annual meeting. But in my humble opinion, the most rewarding way of getting involved is to volunteer your time and join a committee. I have served on various committees including the Executive Council, the Communication and Media Committee, the Nominating Committee, the Constitution and Bylaws Committee, as well as the Program Committee. I learned a great deal via my involvement on these committees and I like to think that through this participation, I have contributed to the development of the Society.

Weather you are a trainee, an associate member or a regular member, I encourage you to go to the ASA website, pick a committee (or 2!) and contact the committee chair. Don’t hesitate to ask questions about what is expected from committee members. For most committees, being a member means a few teleconference meetings throughout the year   and an face to face meeting at the ASA Annual Meeting. There is always room for members willing to volunteer their time for the Society. And the reward is well worth it!

In case you missed it there are openings available on ASA committees.

Jacques J. Tremblay
Universite Laval
Quebec, Canada

Featured Research Break-Through of Dr. Monika Ward, Professor, Institute for Biogenesis research University of Hawaii

Edited by fellow ASA member and Chair of the Communications and Media Committee, Sarah Kimmins

ASA member, Professor Monika Ward and her team have conducted a series of experiments revealing new insights into Y chromosome gene function and evolution. In this new study published in Science on January 29, 2016, Ward and her colleagues describe how they generated Y-less males and demonstrate their ability to produce gametes and sire offspring. In these males, the two Y genes that are essential for the development of testes and male gametes were replaced with their homologues encoded on other chromosomes.The researchers replaced the Y chromosome gene Sry with its homologue and direct target Sox9.  In normal development, Sry turns on Sox9, and this initiates a series of differentiation events that allow an XY fetus to develop into a male.  Yamauchi et al., used a transgenic approach to activate Sox9 in the absence of Sry. Next, they replaced the second essential Y chromosome gene, Eif2s3y, with its X chromosome encoded homologue, Eif2s3xEif2s3y and Eif2s3x belong to the same gene family and are very similar in sequence. The researchers speculated that these two genes may play similar roles, and it is a global dosage of both that matters. They transgenically overexpressed Eif2s3x, increasing dose of the X gene beyond that provided normally by X and Y.  Under these conditions, Eif2s3x took over the function of Eif2s3y in initiating spermatogenesis.

Finally, Ward's team replaced Sry and Eif2s3y simultaneously, and created XOSox9,Eif2s3x males that had no Y chromosome DNA. Mice lacking all Y chromosome genes developed testes populated with male germ cells. Round spermatids were harvested and round spermatid injection (ROSI) was used to successfully fertilize oocytes. The offspring derived from the "No Y" males were healthy and lived for normal life span. The daughters and grandsons of the "No Y" males were fertile and capable of reproducing on its own without further technological intervention. Ward's team produced three consecutive generations of "No Y" males using ROSI showing that males lacking Y chromosome genes can be repeatedly propagated with technical assistance. These studies show that when assisted reproduction is used, the Y chromosome contribution is not necessary.
In humans, ROSI is considered experimental due to concerns regarding the safety of injecting immature germ cells and other technical difficulties.  Ward hopes that the success in mouse studies may spark the re-evaluation of human ROSI for its suitability to become an option for overcoming male infertility in the future.

Ward provided us with some insight into this groundbreaking work and gave us a behind the scenes view of some of the challenges faced.

1. What led your group to perform this series of transgenic experiments and what was the most difficult aspect of the study and how did your group overcome it?

Our primary interest is in investigating the function of Y chromosome genes. But the Y chromosome is particularly resistant to unveiling its secrets and conventional gene knockout strategies were not applicable for this chromosome. Consequently, our work, and work of others interested in Y, was based on the analyses of Y mutations (primarily deletions) and, in the mouse, on transgenic rescue studies in which the deleted genes were added back. We followed this strategy to learn about the function of Y chromosome genes. “Minimizing Y” was an extreme form of transgene rescue, in which single Y genes were added to mice lacking the Y chromosome. After we identified two minimal Y chromosome genes compatible with successful assisted fertilization 2 years ago, the natural next step was to see if those genes could be replaced by non-Y genes. We were particularly excited in exploring the X-Y gene pair (Eif2s3yEif2s3x). We knew that the Y gene is very important and is absolutely required for spermatogenesis initiation. Our finding that this key function can be taken over the X gene is an important finding pertinent to discussion on Y chromosome evolution.

In the course of our work we observed an interesting phenomenon. One transgene copy of the X gene was sufficient to initiate spermatogenesis but was not enough to drive it through meiosis. For that we needed at least 4 copies. As reported by others, in spermatogenic cells from normal XY males, Eif2s3y is more abundant (5 – 7 times) than Eif2s3x. So at least for this gene pair, the Y gene does not seem to be degenerating or decaying and the X gene is not compensating. On the contrary, it seems that strong expression of the Y gene evolved to meet the needs of spermatogenesis.

The most difficult aspect of the study was generating mice with single and no Y chromosome genes. The breeding necessary to place the transgenes in a right combination and in a context of a single X chromosome is highly inefficient. It requires breeding XO females and the resulting litters are often small, not to mention that a chance to obtain a genotype of interest is 12.5% (1 out of 8 possible). So it took a lot of time to obtain a sufficient number of mice for analyses. Furthermore, not all of them were suitable for assisted reproduction trials. Finding round spermatids for injections was true tour de force. But altogether, it was a great and rewarding project, highly enjoyed by all involved. The excitement after first offspring were obtained from males lacking Y paid off all the difficulties.

2. What do the study results mean in terms of advancing our understanding of sex determination and is SRY still all important in male sex determination?

Sry is still the master regulator of male sex determination. But it is just a switch which turns on this complex pathway, and as such it is easy to replace. Sox9 is first in-line after Sry, and its direct target. It has been known before that when Sox9 expression is altered, either spontaneously or using transgenic/knockout strategies, this leads to sex reversal. XX mice develop as males when Sox9 is transgenically activated. But presence of two X chromosomes and lack of essential Y chromosome genes are not compatible with spermatogenesis. So we took it farther and explored Sox9-driven sex determination in the context or a single X and a single essential Y gene, Eif2s3y. When this worked, we substituted Eif2s3y for its X-chromosome homologue, allowing for the development of males lacking all chromosome genes.

Transgenic activation of Sox9 is one of many examples of an alternative pathway driving sex determination. Manipulation of expression of other genes from the SOX family (Sox3, Sox8, and Sox10) as well as other genes (e.g. Dax1, Dmrt1/2, Rspo1, Fgfr2, FoxL2, Cbx2, Map3k1/4, Igfr1, and other) have been shown to result in the sex fate change. This further reinforces the idea on plasticity of sex determination pathway and indicates that there are many ways to bypass the primary Sry-based sex fate.

Some Highlights of the Upcoming Annual ASA Meeting!

See you in New Orleans!

New OrleansNew Orleans, with its richly mottled old buildings, its sly, sophisticated — sometimes almost disreputable — air, and its Hispanic-Gallic traditions, has more the flavor of an old European capital than an American city. Townhouses in the French Quarter, with their courtyards and carriageways, are thought by some scholars to be related on a small scale to certain Parisian “hotels” — princely urban residences of the 17th and 18th centuries. Visitors particularly remember the decorative cast-iron balconies that cover many of these townhouses like ornamental filigree cages.

European influence is also seen in the city's famous above-ground cemeteries. The practice of interring people in large, richly adorned aboveground tombs dates from the period when New Orleans was under Spanish rule. These hugely popular “cities of the dead” have been, and continue to be, an item of great interest to visitors. Mark Twain, noting that New Orleanians did not have conventional below-ground burials, quipped that “few of the living complain and none of the other.”

Attractions

Take a bike ride along the Mississippi River, feed an alligator or stroll through time as you take in the stories behind one of our many historical attractions. New Orleans has so much to offer and caters to every traveler. So whether you're a sports fan, history buff, outdoor adventurer, aspiring chef or music lover, there's an attraction in New Orleans to suit your every need

Shopping

New Orleans shopping — from the French Quarter to Magazine Street — offers an array of retail choices. Options include The Shops at Canal Place, Saks Fifth Avenue, Outlet Collection at Riverwalk, as well as hundreds of boutiques, art galleries and antique stores throughout the city along. Tax-free shopping offers international visitors even more reasons to experience New Orleans.

Dining/Nightlife

New Orleans offers one of the most incredible — and incredibly diverse — concentrations of exceptional dining and unforgettable cuisine in the world.

The night never has to end in New Orleans since bars and clubs are not required to close. In fact, many say the city is at its best under the glow of a French Quarter street lamp. But to suggest the party starts and ends on Bourbon Street sells the rest of the city short. New Orleans has many distinct neighborhoods that offer nightlife options from incredible live music on Frenchmen Street to intimate cocktails just a neighborhood away. Harrah's Casino caters to the high rollers at heart and the city is home to slick nightclubs where you can dance the night away.

Weather

New Orleans has a subtropical climate with pleasant year-round temperatures. Temperatures range from the mid 50's to the upper 70's in April.

Arts & Culture

New Orleans' Old World roots have created a strong foundation and long-standing appreciation for the arts. Early residents of the city often traveled back to Europe for musical instruction or training in the visual arts, and operatic performances took place in the city as early as 1796.

Today the scene thrives via countless galleries, performance spaces and museums. But perhaps what sets our cultural institutions apart from those of other cities is their ability to embody the joie de vivre (joy of life) so prevalent in New Orleans. So whether it is a Ralph Brennan restaurant in the New Orleans Museum of Art or Thursday night musical performances at the Ogden Museum of Southern Art, New Orleans' unique culture and love of food, music and fun blends perfectly with our vibrant arts scene creating experiences you can't find anywhere else

To find out more on New Orleans, please visit the New Orleans Convention & Visitors Bureau

ASA Annual Banquet

Date:Monday, April 4, 2016
Time:7:30 p.m. – 11:00 p.m.
Location:Paddlewheeler Creole Queen
Website:creolequeen.com

Join ASA as we step back into the glamour and romance of the riverboat era with a cruise aboard the Paddlewheeler Creole Queen! Experience the sounds of Jazz while enjoying a lavish Creole Buffet in elegantly appointed dining rooms. After dinner partake in a little dancing or enjoy a classic New Orleans cocktail on the promenade deck viewing the city skyline slips under a canopy of stars. Purchase your ticket when you register for the ASA annual meeting.

2016 Trainee Directed Mini-Symposium
“Eyes Wide Open: Understanding the Ins & Outs of Publishing”

April 3, 2016 4:30 p.m. – 6:30 p.m.

The Trainee Affairs Committee is proud to announce the return of Trainee-Directed Mini-Symposium! The two trainee-elected representatives, Drs. Luke Simon and Mahmoud Aarabi, have led the charge in organizing the latest edition of this professional development event entitled “Eyes Wide Open: Understanding the Ins & Outs of Publishing”. Two sessions have been planned, one touching upon efficient writing of manuscripts, the other on the manuscript review process from various perspectives.

This year, the Mini-Symposium has been integrated in the main program and will take place on Sunday April 3, 2016 from 4:30 pm – 6:30 pm prior to the Trainee Mixer during the Annual Meeting. The Trainee-Directed Mini-Symposium is intended for all basic scientists and clinicians attending the annual meeting, trainees and lab heads alike! We hope to see you there!

For more information and a detailed program, please visit the meeting section of this website.

Additional Programs of Interest to ASA Trainees
  • Careers in Andrology: Developing Careers and Promoting Diversity in the ASA Membership and in the Science and Medicine of Male Reproductive Health. Visit http://www.andrologycareers.org/ for career guidance, news and announcements, interviews with andrologists, and additional information related to the Diversity Initiative of the ASA.
  • Free One-Year Membership for First Time Trainee Presenters at the ASA Annual Meeting. Visit http://andrologysociety.org/Membership/Membership-Benefits.aspx for more details.
  • Mentor-Mentee Program for Senior Graduate Students, Postdocs and Early Stage Investigators. Visit http://www.andrologycareers.org/ for more information on this program. Trainees interested by this mentoring opportunity should fill out the Track 1 Mentee form at http://www.andrologycareers.org/track-1-mentee-form.html. Active Members (Senior Investigators and Clinicians) seeking to become mentors should apply using the Track 1 Mentor Volunteer form.
2016 ASA Trainee Fundraiser Item

Pre-order your 2016 ASA Umbrella before the meeting

ASA Trainee Umbrella

The Trainee Affairs Committee of the American Society of Andrology is proud to announce the launch of new fundraiser items. This year the theme of our fundraising is “Protect Yourself & Others!” presenting umbrellas and condom packs! Proceeds will benefit the Trainee Affairs Committee. Payment will be taken on-site at the 41st ASA Annual Meeting (CASH only).

  • Auto Open Compact Umbrella in Black and White, customized with ASA logo
  • Pre-order now for only $17 when you register for the meeting