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Gamete signalling may explain infertility

What goes on – or what should be going on – in human gametes at the time of conception? This is something researchers of evolutionary biology at the Department of Environmental and Biological Sciences are currently exploring. Infertility may not always be a disease: it can also be a consequence of gamete-level mate choice.

Research into reproductive biology is often considered something that falls in the scope of health sciences or medicine. Now, however, researchers at the University of Eastern Finland are approaching the topic from the viewpoint of evolutionary biology.

A study by Associate Professor of Animal Physiology Jukka Kekäläinen and Senior Researcher Marjo Malinen starts from the idea that diagnosing the causes of infertility can be enhanced by exploring the mechanisms of gamete signalling.

“Nowadays, infertility is divided into male and female dependent pathological factors,” says Malinen, who recently transferred to the Department of Environmental and Biological Sciences from the Institute of Biomedicine.

“However, in up to 30–40 per cent of couples studied, it is impossible to say whether infertility is of male or female origin.”

 “Traditionally, mate choice is thought to take place in the individual level, but we are wondering if there could also be mate choice between gametes. Our study seeks to explore whether biochemical signalling between gametes could serve as a mechanism of mate choice by increasing the probability of conception in couples who are compatible at the level of gametes,” Kekäläinen notes.

“Often, infertility is not caused by weak male or female gamete quality, but rather by the fact that certain immunological factors may make the gametes of some couples less compatible than those of others. However, gamete incompatibility does not imply that a couple would be otherwise incompatible, for instance in terms of their personality.”

“This is the first time gamete-level mate choice is studied in humans at the molecular level. The moment of conception is basic biology but, surprisingly, we still don’t know much about it.  For instance, the receptor-level mechanisms at play in eggs and sperm at the time of conception are practically unknown.”

Everyone can find a compatible partner

In a recent experiment by the research group, sperm donated by eight men was mixed with ovarian follicle fluid donated by ten women.   

Sperm were analysed for various physiological changes in different male-female combinations with the help of computer-assisted video analysis and different fluorescent cell staining methods. The analyses provided detailed insight into how sperm prepare for fertilisation in different male-female combinations. 

“We noticed that sperm from specific donors had much higher motility in the ovarian follicle fluid of some women than others. In line with our hypothesis, this suggests that the gametes of a specific man or a woman are not likely to be equally compatible with the gametes of everyone of the opposite sex,” Kekäläinen concludes. 

“Although these findings suggest that gamete-level mate choice plays an important role at the time of conception, it is still possible that even couples who are compatible in terms of their gametes will have problems to conceive,” Malinen notes.

“However, it has been observed that certain physiological changes induced by the ovarian follicle fluid in sperm predict successful conception,” Kekäläinen says.

The study was carried out in collaboration with Liisa Kuusipalo, PhD, and staff of the obstetrics clinic of the North Karelia Central Hospital. Kuopio University Hospital will also provide samples for the other sub-projects of the study.

 “Collaboration with clinical staff working in hospitals is vital to us researchers. Without them, our work would not be possible,” Kekäläinen points out.

 “We’d also like to thank all the volunteers who have open-mindedly participated in our study, despite their difficult situation in life.”

Infertility is not necessarily permanent

Getting a diagnosis of infertility doesn’t usually mean that having children is impossible. For instance, as one’s life changes following a successful in vitro fertilisation, the next child may well be conceived naturally.

“It is possible that this phenomenon, too, is immunological in nature and possibly linked with the function of so-called memory cells of the immune system. These cells are also what makes vaccinations work,” Kekäläinen explains.

“It is interesting to speculate whether gamete signalling, compatibility and successful conception could be influenced in a manner similar to vaccination.”

 “This could also open up opportunities for the development of novel contraceptives,” Malinen adds.

Fertilisation treatments come with much uncertainty, costs and stress. This is why one of the main objectives of the study is to lay the foundations for increasingly accurate methods for diagnosing infertility. This would reduce insecurity and stress in couples suffering from infertility, as well as treatment-related costs.

Yet, it is worth bearing in mind that the causes of infertility are complex. For example, environmental toxins, overweight and too warm or tight clothes have been associated with reduced fertility. According to the researchers, also a person’ diet – and other lifestyle habits in general – can induce changes in gametes and thus improve the probability of successful conception.

 “In the future, we will focus on the role of vitamin D and endocrine disruptors, such as bisphenols and phthalates, in infertility and gamete signalling,” they say.

 “We expect to publish findings from our gamete signalling study in the autumn.”