Reproductive Health

Why we need to make more of an effort to understand sperm

Sperm are the key to the future of fertility – and contraception.

Despite the huge global demand for both fertility treatment and contraception, there are surprisingly few options to boost male fertility, or for male contraception. To have more options, we really need a better understanding of how human sperm work. Unfortunately, they are incredibly difficult to study in the lab.

Not only are sperm the smallest cells in the body (25 times smaller than a grain of sand), they are unique and highly specialised, designed to survive outside the body. Unlike other cells, sperm contain virtually no cytoplasm – the jelly-like fluid that fills a cell and stores many of the chemicals that are essential for life. Instead they interact with the surrounding environment to inform their behaviour. Their internal chemical messages and signals are also different to those of other cells, meaning we can’t make assumptions about how they work and many standard cell research techniques can’t be applied in the lab. It’s little wonder then that research in the field of male fertility and contraception is limited.

Growing infertility

Infertility is estimated to affect about one in seven couples of reproductive age in the United Kingdom. Male fertility problems are increasingly common. However, our limited understanding of how sperm work and the requirements needed to achieve fertilisation, means that we struggle to treat this problem.

Incredibly, there is no drug that an infertile man can take, or that can be added to his sperm in a laboratory to improve how sperm swim or work. Instead couples rely on treatments such as in vitro fertilisation or IVF and intracytoplasmic sperm injection or ICSI, which are expensive, invasive, and not guaranteed to succeed. Nonetheless, the number of people seeking IVF and ICSI treatment is increasing each year.

Although access to female contraception varies considerably across the globe, use of male methods (condoms, vasectomy) is consistently low. There has been no significant innovation in available male contraception in the past 50 years. Hormonal and non-hormonal methods have been researched since the 70s, but side effects were too severe for implementation.

An immobilized ejaculated spermatozoon is inserted into a human oocyte. (Image: Eugene Ermolovich/Wikimedia Commons)
An immobilized ejaculated spermatozoon is inserted into a human oocyte. (Image: Eugene Ermolovich/Wikimedia Commons)

New, safe, effective and acceptable contraceptive methods for men would help to address the needs of couples who do not, or cannot, use currently available methods. Having a wider choice of contraceptives is also known to increase uptake of all methods. Perhaps more significant is the potential to give men increased options in family planning, leveling the gender inequality in this area.

Silent swimmers

There is a real demand – and an unmet need – for the development of new treatments for both male infertility and family planning. But, before we can tackle these global health issues, we need to understand how sperm work. Without this detailed knowledge, and a potential target for a drug to work on, it is virtually impossible to develop new compounds to enhance, or inhibit, sperm function.

Sperm swimming (motility) is probably its most important characteristic. Although the underlying cellular mechanisms are not fully understood, changes in levels of calcium inside the sperm cell are known to be crucial to sperm function, including swimming and fertilisation. Fluctuations in the level of calcium within sperm cells is known to be due to specific membrane pores (ion channels) in the sperm tail – these pores are called CatSper.

A swimming sperm. From video by Kantsler et al. (CC BY 3.0)
A swimming sperm. From video by Kantsler et al. (CC BY 3.0)

High-throughput screening or HTS is an approach used by the pharmacology industry to discover new drugs, where automated experiments can examine thousands of compounds to “screen” for a desired effect. Compounds that show the desired effect are called “hits”.

We recently published a paper describing a HTS approach to look for new drugs to treat male infertility. Calcium inside sperm was fluorescently labelled, and levels then measured in response to a number of new drug compounds.

We screened more than 3,400 compounds and identified 48 hits, that showed the effects we needed. Further testing of several of these hit compounds found two that showed improved function and swimming in sperm, probably due to an effect on CatSper channels.

A potential cure

Although the original experiments used sperm from healthy volunteers, the researchers also saw enhanced function and swimming when they tested both compounds on samples from patients undergoing IVF. Given the lack of progress in treating male infertility to date, this is a promising find, even if it is very early days.

The beauty of this finding is that the compounds that we found would only act on sperm cells, because the ion channel “CatSper” is unique to sperm. This could help to avoid unwanted side effects, which makes these compounds attractive clinically and commercially. While this research has been directed at drug discovery for male fertility, it is possible to turn the concept around and find compounds that inhibit sperm swimming, thereby creating a new male contraceptive.

This is an advance that potentially offers hope to millions of couples worldwide, but there is still much that we need to know and understand to unlock the workings of the human sperm.

Sarah Martins da Silva, Consultant Gynaecologist and Senior Lecturer In Reproductive Medicine, University of Dundee.

This article first appeared on The Conversation.

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Relying on the power of habits to solve India’s mammoth sanitation problem

Adopting three simple habits can help maximise the benefits of existing sanitation infrastructure.

India’s sanitation problem is well documented – the country was recently declared as having the highest number of people living without basic sanitation facilities. Sanitation encompasses all conditions relating to public health - especially sewage disposal and access to clean drinking water. Due to associated losses in productivity caused by sickness, increased healthcare costs and increased mortality, India recorded a loss of 5.2% of its GDP to poor sanitation in 2015. As tremendous as the economic losses are, the on-ground, human consequences of poor sanitation are grim - about one in 10 deaths, according to the World Bank.

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According to the World Bank, hygiene promotion is essential to realise the potential of infrastructure investments in sanitation. Behavioural intervention is most successful when it targets few behaviours with the most potential for impact. An area of public health where behavioural training has made an impact is WASH - water, sanitation and hygiene - a key issue of UN Sustainable Development Goal 6. Compliance to WASH practices has the potential to reduce illness and death, poverty and improve overall socio-economic development. The UN has even marked observance days for each - World Water Day for water (22 March), World Toilet Day for sanitation (19 November) and Global Handwashing Day for hygiene (15 October).

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This touching film made as a part of SASB’s awareness campaign shows how lack of knowledge of basic hygiene practices means children miss out on developmental milestones due to preventable diseases.

Play

SASB created the Swachhata curriculum, a textbook to encourage adoption of personal hygiene among school going children. It makes use of conceptual learning to teach primary school students about cleanliness, germs and clean habits in an engaging manner. Swachh Basti is an extensive urban outreach programme for sensitising urban slum residents about WASH habits through demos, skits and etc. in partnership with key local stakeholders such as doctors, anganwadi workers and support groups. In Ghatkopar, Mumbai, HUL built the first-of-its-kind Suvidha Centre - an urban water, hygiene and sanitation community centre. It provides toilets, handwashing and shower facilities, safe drinking water and state-of-the-art laundry operations at an affordable cost to about 1,500 residents of the area.

HUL’s factory workers also act as Swachhata Doots, or messengers of change who teach the three habits of WASH in their own villages. This mobile-led rural behaviour change communication model also provides a volunteering opportunity to those who are busy but wish to make a difference. A toolkit especially designed for this purpose helps volunteers approach, explain and teach people in their immediate vicinity - their drivers, cooks, domestic helps etc. - about the three simple habits for better hygiene. This helps cast the net of awareness wider as regular interaction is conducive to habit formation. To learn more about their volunteering programme, click here. To learn more about the Swachh Aadat Swachh Bharat initiative, click here.

This article was produced by the Scroll marketing team on behalf of Hindustan Unilever and not by the Scroll editorial team.