The secret of fertile sperm

To better understand the causes of male infertility, a team of Bay Area researchers has been exploring the factors, both physiological and biochemical, that differentiate fertile sperm from infertile sperm. At the 58th Annual Biophysical Society Meeting, which took place Feb. 15-19, 2014, in San Francisco, Calif., the team presented its work to identify and characterize proteins known as ion channels, which are crucial for sperm fertility and expressed within a sperm cell's plasma membrane. "Any knowledge gained in this area may help create much-needed diagnostic testing and treatments for male infertility, which is in essence an idiopathic disease, because at this time 80 percent of male infertility cases can't be diagnosed or treated," said Melissa Miller, a postdoctoral fellow who will present the team's findings at the meeting. Miller works in the labs of both of her co-authors, Polina Lishko of the University of California, Berkeley (UCB), and Yuriy Kirichok at the University of California, San Francisco (UCSF). To study ion channels, the researchers are recording the electrical activity of sperm ion channels under strictly controlled conditions. "Our labs have characterized three ion channels re sponsible for regulating calcium (CatSper), potassium (Slo1), and protons (Hv1) within sperm cells," Miller said. "So far, the most well-studied is the sperm cation channel CatSper, which is exclusively expressed within sperm cells and represents an ideal target for development of a unisex contraceptive; no other cell in the body is known to express this protein." "We recently reported that the female hormone progesterone activates CatSper via a non-genomic pathway. In normal fertile spermatozoa, CatSper activity was greatly increased by the addition of progesterone. However, patch clamp recording from patient-derived sperm cells with CatSper deletion showed no response to progesterone nor did they produced basal CatSper current," Miller said. "This shows direct regulation of the CatSper channel in human sperm by steroid hormones." Steroid hormones control the fundamental physiological functions via both traditional genomic and unconventional, nongenomic pathways. Previous research established that nongenomic signaling plays a vital role in both human sperm cell activation and pain perception modulation within neurons of the spinal cord. Because the molecular determinants of this pathway are poorly understood, Miller's team is working to uncover the precise molecular signaling cascade that occurs in sperm cells and neurons upon progesterone treatment. "The lack of CatSper activity is strongly correlated with male infertility, so identification of this endogenous signaling molecule would give us a novel biomarker for male fertility that could be immediately used in the clinic as a way to quickly assess sperm fertilization potential," Miller said. Overall, the knowledge gained from the team's studies may be used in the future development of new pain management therapies, as well as diagnostic tests and treatments for male infertility.

Frequently Asked Questions

What are sperm ion channels and why do they matter for male fertility?

Ion channels are specialised proteins found in the membrane of sperm cells that regulate the movement of calcium, potassium, and protons. These channels are essential for healthy sperm function, including motility and the ability to fertilise an egg. Research into ion channels like CatSper may lead to new diagnostic tests and treatments for male infertility, which currently affects around 1 in 7 UK couples trying to conceive.

Can the NHS test for sperm ion channel problems?

Currently, NHS fertility testing focuses on standard semen analysis, which examines sperm count, motility, and morphology as recommended by NICE guidelines. Testing for specific ion channel function is still largely within the research phase and not routinely available through NHS fertility clinics. If you're concerned about male factor infertility, your GP can refer you for initial investigations after 12 months of trying to conceive.

Why can't doctors diagnose most cases of male infertility?

Research suggests that around 80 percent of male infertility cases remain unexplained or idiopathic, meaning the underlying cause cannot be identified with current diagnostic tools. Scientists are working to understand the biochemical factors, such as ion channel function, that differentiate fertile sperm from infertile sperm. This ongoing research may eventually lead to better diagnostic testing available through fertility services.

How does progesterone affect sperm and fertilisation?

Progesterone, a hormone released by the female reproductive system, has been shown to activate the CatSper ion channel in sperm cells through a non-genomic pathway. This activation increases sperm activity and is thought to play a crucial role in guiding sperm towards the egg for fertilisation. Understanding this process could help researchers develop new fertility treatments and even novel forms of contraception.

What should I do if we've been TTC for over a year with no success?

According to NHS guidelines, you should speak to your GP if you haven't conceived after 12 months of regular unprotected intercourse, or sooner if you're over 36 or have known fertility concerns. Your GP can arrange initial tests including semen analysis for the male partner and refer you to a fertility specialist if needed. Be aware that NHS funding criteria for fertility treatment vary by local Clinical Commissioning Group (CCG), so it's worth checking your area's specific eligibility requirements.

Will there be new treatments for male infertility based on this research?

Researchers are hopeful that understanding sperm ion channels could lead to targeted treatments for male infertility in the future. As the CatSper channel is only expressed in sperm cells, it represents a promising target for both fertility treatments and potential unisex contraceptives. However, these developments are still in the research phase and not yet available through NHS or private fertility clinics in the UK.

How can I support healthy sperm while trying to conceive?

The NHS recommends maintaining a healthy lifestyle to support sperm quality, including eating a balanced diet, exercising regularly, reducing alcohol intake, and avoiding smoking. Fertility supplements containing key nutrients may also help support overall reproductive health. If you have concerns about sperm quality, speak to your GP who can advise on appropriate testing and potential referral to a fertility specialist.