Men with fertility issues have lower levels of phosphate in the blood than average, according to research presented at the first Joint Congress between the European Society of Paediatric Endocrinology (ESPE) and the European Society of Endocrinology (ESE). In addition, low phosphate concentrations in the blood were associated with reduced sperm motility in infertile men. The findings can help researchers improve the understanding of the biological factors involved in male reproductive health, which could lead to new fertility treatments.
Over the past 50 years, sperm counts worldwide have halved, sperm quality has declined alarmingly and 15% of all heterosexual couples are facing infertility. Male infertility contributes to approximately half of all cases of infertility, but for the majority of men with fertility issues, the cause remains unexplained. However, many factors — including genetics, lifestyle and nutritional choices, and hormonal imbalances — can affect men's fertility. For example, in recent years, vitamin D deficiency has been linked with poor semen quality.
In this study, researchers from the Copenhagen University Hospital Herlev and the Copenhagen University Rigshospitalet analysed blood and semen samples from 1,242 men with infertility in Denmark. They found that 36% of these men had clinically low levels of phosphate in their blood, as opposed to the approximate 2–4% incidence found in the general population in Denmark. Men with moderately low phosphate levels had fewer motile and progressively motile sperm compared to those with normal phosphate levels. In addition, the men with moderately low phosphate levels had slightly higher levels of the hormone estradiol. Low levels of phosphate were not associated with sperm count.
"Surprisingly, we identified, for the first time, that the percentage of infertile men with low phosphate concentration in the blood is higher than that of the general Danish population," said lead author Dr Sam Kafai Yahyavi.
Dr Kafai Yahyavi added: "This could mean that phosphate — a mineral which has known effects in energy production and bone strength — has a potential to be targeted directly to potentially improve fertility, possibly by treating some of the infertile men with phosphate supplements."
"While our study does not prove that low phosphate concentrations cause infertility, it highlights a potential connection that could be important for understanding and treating male infertility," said Dr Kafai Yahyavi.
The team has also previously found that phosphate is essential for testicular function in healthy men, as phosphate concentrations in the seminal fluid are more than 20-fold higher than in the blood, implying that phosphate is regulated within the male reproductive system. With this in mind, in another study, also presented at the Joint Congress of ESPE and ESE, Dr Kafai Yahyavi and colleagues investigated this phosphate transport mechanism in rodents and humans and found that high phosphate levels in human semen were associated with higher-quality sperm and increased testosterone levels.
"Our study suggests that phosphate levels in the reproductive organs may be important for organ function and sperm function, and we are now searching for regulators of this transport and through them, the influence on male fertility," said first author Ms Zhihui Cui, a PhD student at the Copenhagen University Herlev Hospital.
Dr Kafai Yahyavi said: "This is exciting because this transport mechanism now raises the question of whether manipulating phosphate concentrations in the blood will affect fertility. Therefore, our next step of research is to start controlled trials, in which phosphate is used as an intervention, in order to assess the direct effect of phosphate on fertility in men — but also in women."
