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No NELL2, no sperm motility; novel protein is essential for male fertility

Male infertility may arise from lack of communication between the testis and the epididymis and new research has uncovered a mechanism of this communication.

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Photo by Dainis Graveris from Unsplash.com

Newly produced spermatozoa within the testis are not fully functional until they mature in the epididymis, a duct that helps to transport and store sperm. Male infertility may arise from lack of communication between the testis and the epididymis and new research has uncovered a mechanism of this communication.

Dr. Martin Matzuk at Baylor College of Medicine, Dr. Masahito Ikawa with Osaka University and their colleagues have discovered a novel testicular luminal protein, NELL2, that triggers in the epididymis a chain of events that matures the sperm and enables each one to be motile in females.

Sperm production

Sperm are produced in the seminiferous tubules of the testis and move through the epididymis, a long, convoluted tube linked to the vas deferens, the duct that moves sperm from the testicle to the urethra. When the sperm enter the epididymis, they are not motile and are incapable of fertilization. However, in their passage through the epididymis, the sperm are provided an appropriate environment for maturation and storage pending ejaculation.

It has been hypothesized that proteins released by the testis earlier in this process could act on the epididymis to mature the sperm as they arrive in the epididymis.

“Until now the proteins working through the lumicrine system of signaling have remained elusive. While it was known that the orphan receptor tyrosine kinase ROS1 expressed in the initial segment of the epididymis is necessary for its differentiation, neither the testicular factors that regulate initial segment differentiation nor the process of sperm maturation had been fully understood,” said Matzuk, professor and director of the Center for Drug Discovery at Baylor.

Identifying NELL2

The researchers zeroed in on NELL2, a protein factor secreted by testicular germ cells, as a possible lumicrine regulator of fertility. “Using innovative genome editing technology, we generated knockout mice lacking the NELL2 gene and showed that these knockout males are sterile due to a defect in sperm motility,” explains lead author Dr. Daiji Kiyozum. “Moreover, their infertility could be rescued with a germ-cell-specific transgene, thus excluding other sites of expression. We also illustrated lumicrine signaling by demonstrating tagged NELL2 in the epididymal lumen.”

The research team observed that spermatogenesis proceeds normally in NELL2 knockout mouse testes but their epididymis was poorly differentiated, similar to Ros1 knockout mice. Following mating, neither NELL2 knockout nor Ros1 knockout spermatozoa can enter the uterine tubes or fertilize an egg. Further investigation showed that the Nell2 knockout epididymis is incapable of processing a specific sperm surface protein essential for male fertility.

Implications for male fertility?

Elaborating on their study, Ikawa and Matzuk, both senior authors, said, “We discovered a complicated cascade of events in which disruption of any point in this lumicrine pathway causes a male to be infertile. Our findings have important translational implications for diagnostic and therapeutic research in male infertility and male contraceptive development. This unique transluminal communication pathway between tissues and organs likely functions elsewhere in our bodies.”

Others who contributed to the work include Taichi Noda, Ryo Yamaguchi, Tomohiro Tobita, Takafumi Matsumura, Kentaro Shimada, Mayo Kodani, Takashi Kohda, Yoshitaka Fujihara, Manabu Ozawa, Zhifeng Yu, Gabriella Miklossy, Kurt M. Bohren, Masato Horie and Masaru Okabe.

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DKT Philippines Foundation unveils PH’s first family planning mobile clinic

The SODEX Mobile Clinic is an innovation to improve DKT Philippines Foundation’s SODEX Program and its contribution to achieving the DOH 8-Point Action Agenda and National Objectives for Health.

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DKT Philippines Foundation, a charitable non-profit organization promoting family planning and HIV prevention, officially launched the SODEX (Service Outreach and Distribution Extension Program) Mobile Clinic – the country’s first-ever family planning ambulatory clinic. This pioneering effort aims to provide safe and accessible modern family planning methods for Filipinos in far-flung areas to bridge the gap between Filipinos wanting to space and limit pregnancy and the disparities in Family Planning service provision.

The SODEX Mobile Clinic is an innovation to improve DKT Philippines Foundation’s SODEX Program and its contribution to achieving the DOH 8-Point Action Agenda and National Objectives for Health.

“DKT Philippines Foundation’s mission is to provide couples with affordable, and safe options for family planning, and HIV/AIDS prevention through dynamic social marketing,” said Loida Almendares, the Foundation’s Director of Programs. “The SODEX mobile clinic will provide a wide array of free family planning services especially in areas with lesser access to services like the geographically isolated or socially disadvantaged areas. The mobile clinic will bring the services closer to the people and meet them where they are,” she added.

The mobile clinic will provide free Family Planning commodities such as pills, condoms, injectables and intrauterine devices (IUD). It will also offer free bilateral tubal ligation (BTL) using local anesthesia and non-scalpel vasectomy (NSV). Onboarding the clinic are Physician/Surgeon trained on the provision of BTL, NSV, IUD, and subdermal implant services; FP-trained nurse; FP- trained midwife; a circulating staff, and a driver. To ensure that all clients are well-informed and fit to take the services, they will undergo counseling and final screening prior to getting the method.

In partnership with 30 LGUs from Luzon, DKT Philippines Foundation aims to foster sustainable and long-term partnerships with these LGUs to cultivate Filipinos’ desire to meaningfully participate and contribute to government efforts to achieve universal health coverage for all.

“DKT Philippines Foundation and its Family Planning Mobile Clinic reinforce DKT’s commitment to ensuring nobody is left behind and provides free and quality reproductive health options including permanent methods, to those most remote and vulnerable communities. Made possible by the sales of family planning products under the TRUST Reproductive Health Choices brand, the mobile clinic ensures that people who still cannot afford the highly affordable TRUST products, or cannot access the reproductive health services they need in the public sector, are not left behind and still have free access to these services. It is a part of a total market approach, complementing the important work the local LGUs do on a daily basis.” said Denise van Dijk, Chair of the Board of DKT Philippines Foundation.

The mobile clinic will travel for 119 days to offer free services in the provinces of Central Luzon, North Luzon, Cordillera, MIMAROPA and CALABARZON with the first stop being at Binangonan, Rizal where the launch took place. The clinic will stay in one area for a day or two from 8 AM to 6 PM. By next year, the mobile clinic will cover communities in the Visayas and Mindanao areas. 

The launch and blessing event was officially attended by fellow reproductive health advocates in public and private sectors, development partners, and family planning clients.  Guest of honor and speaker was Department of Health Undersecretary Dr. Glenn Mathew Baggao with special participation of the Mayor of Binangonan, Rizal – Hon. Cesar M. Ynares.

The programs and free services of DKT Philippines Foundation are made possible by the country’s leading brand of contraceptives TRUST Reproductive Health Choices, which is carried by the social enterprise DKT Health, Inc.

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Pru Life UK ramps up recruitment efforts

Through a series of Build Your Business (BYB) sessions—held online and in person in key cities across the country—seasoned PRU business builders share their success stories and tips to encourage attendees to pursue their own business goals.

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Pru Life UK ramps up its recruitment efforts to empower ambitious individuals from all walks of life to build a long-lasting business with the leading life insurer.

Through a series of Build Your Business (BYB) sessions—held online and in person in key cities across the country—seasoned PRU business builders share their success stories and tips to encourage attendees to pursue their own business goals.

“By choosing Pru Life UK, aspiring financial advisors can be confident that they are backed by the #1 life insurer in the country with strong market presence and solid financial results,” said Marylin Detalla-Averia, Chief Agency Officer of Pru Life UK.

The company ranks number one in the life insurance industry in the Philippines, garnering the highest New Business Annual Premium Equivalent based on the Insurance Commission’s report as of 31 December 2023.

“Our financial advisors are provided with all the support they need to help build their business. They have access to digital tools, development programs, hip offices, and attractive rewards and incentives with unlimited earning potential. This allows them to be their own boss and live their ideal lifestyle while helping clients achieve theirs.”

Celebration of success with #BuildYourPRUBusiness

While BYB sessions are held year-round, the company leads an energetic approach to recruitment this May.

Themed Paint the Town Red: It’s PRUFiesta time, Recruitment Never Stops!, BYB sessions will be held in  Metro Manila (Makati, Ortigas, QC), Pampanga (Clark, Sta. Rosa), South (Alabang, Lipa), North (Baguio), and VisMin (Cebu, Davao, CDO).

Attendees will receive mentorship on becoming a business builder with Pru Life UK’s 40,000-agency force, the largest in the industry.

A virtual BYB session will happen on May 22 featuring “Pambansang Wealth Coach” Chinkee Tan, who will talk about financial management and business development, further highlighting the importance of financial planning and empowering entrepreneurial mindset.

Pru Life UK also holds its weekly Facebook live Q&A sessions for budding and experienced business builders. Held every Thursday at 7:00 p.m., these online sessions offer a glimpse into the world of financial advisors. 

Seeking a meaningful and rewarding business opportunity? Visit bit.ly/JoinPRU2024 to join Pru Life UK’s BYB sessions.

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BAFI, USAID deliver biodiversity projects, MIND S-COOL TV and Biodiversity Crisis Escape Room

Both projects serve to innovatively highlight the critical concepts of “roles” and “collaboration” in addressing the biodiversity crisis as well as the “measures” of the values, not only monetary, that we should all consider living with nature.

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Bonifacio Art Foundation, Inc. (BAFI) and the United States Agency for International Development have joined forces to bring you a two-part biodiversity special of MIND S-COOL TV as well as a traveling Biodiversity Crisis Escape Room (BCER). Both projects serve to innovatively highlight the critical concepts of “roles” and “collaboration” in addressing the biodiversity crisis as well as the “measures” of the values, not only monetary, that we should all consider living with nature.

BCER is the first, traveling, experiential, immersive space, made up of 3 main rooms that will stand for the biodiversity crisis. The goal is for the participants to escape the crisis TOGETHER by helping one another realize and fulfill their roles. BCER will be hosted by BAFI’s The Mind Museum right after its opening at the museum on May 22 and will travel to host venues in Subic (Harbor Point, June15), Puerto Princesa (Robinson’s Mall, June 29) and Davao (Abreeza Mall, July 27) to enjoin participants who include – legislators, enforcers, regulators as well as community leaders – including cultural leaders AND local flora and fauna as well in the form of life-sized moving puppets, manned by professional puppeteers. It will also welcome the general public to experience this very unique and meaningful escape room on the dates mentioned.

Inside BCER, participants will take on roles that they would randomly pick. They will enter 3 connected rooms that they could only escape from if they understand what needs to be done and that they work together. The challenges they will face in each room are closely tied to realizing the “Mga Sukat ng Kalikasan” (measures/values of nature) in order to escape the biodiversity crisis. The experience will be facilitated so it will mimic the real human conversations and actions that need to happen in decision-making involving our natural heritage in which we all share in terms of not just benefits but also responsibilities. 

The 2-part biodiversity special of MIND S-COOL TV, the #1 science show across all channels[1] is a TV version of BCER fleshing out a narrative that will involve our main questers as well as non-human “players” who will be called to help out since MIND S-COOL has been held hostage by the biodiversity crisis. They will experience being trapped in the rooms together with other characters, including life-sized puppets that represent non-humans such as flora, fauna, habitats, abiotic elements giving nature a “voice”. The story of this special 2-part can be summarized as “all life is embedded in nature and we need to realize its many values because if we don’t, the quality of our interconnected lives will be degraded.”  Part 1 of this special will air on May 26, 11 am and replayed at 4:30 PM on OnePh Channel on Cignal while part 2 will air the week after. These will be followed by replays for 6 weeks.

Kathy Wachala, Chief of Party for USAID’s Sustainable Interventions for Biodiversity, Oceans and Landscapes (SIBOL) project, says: “This partnership with BAFI to do BCER and MIND S-COOL TV enabled us to roll-out a very powerful way for stakeholders to internalize their actual roles and work together to come up with solutions to the biodiversity crisis.” Maria Isabel Garcia, Managing Director/Curator of BAFI, also comments on the project, saying, “We are so inspired by the kind of partnership we have with USAID SIBOL since it allowed us to recruit very imaginative ways of engagement for science to serve life, biodiversity.”

We can all escape the biodiversity crisis if we understand that all lives are interconnected and that we all work together, now.

To know more about the USAID SIBOL project and its interventions, you may send an email to info@ph-sibol.org.

Mind S-Cool TV and Biodiversity Crisis Escape Room were conceived and created by the Bonifacio Art Foundation, Inc., the creator and operator of The Mind Museum and the BGC Arts Center.

To know more, or if you wish to know how you can support mind s-cool and the other projects of the Bonifacio Art Foundation, send an inquiry to: mindscool@bafi.org.ph, inquiry@themindmuseum.org or info@bgcartscenter.org.


[1] According to the latest Nielsen Ratings Survey

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