CRIS – shedding light on male infertility

Infertility affects approximately 10% of the population. In 40% of the cases, infertility can be attributed to male factors. The underlying causes are diverse; however, in almost 50% of the cases, there is no apparent cause – it is idiopathic. Defects in sperm development have been associated with idiopathic infertility. Thus, it is important to identify the key proteins during sperm development and understand their physiological function.

We identified one of the key players for sperm development, called CRIS (cyclic nucleotide receptor involved in sperm function). CRIS is an entirely new member of the family of cyclic nucleotide-binding proteins. To unravel CRIS function, we generated CRIS knock-out mice that lacked the Cris gene and, thereby, did not produce the CRIS protein. Whereas CRIS knock-out females are fertile, CRIS knock-out males display a severe fertility defect. The majority of CRIS knock-out males did not produce any sperm – they were completely infertile. However, some of the males had sperm, but their swimming behavior was characteristically different from normal sperm: the sperm tail was bending in only one direction and not, as observed in normal sperm, symmetrically in both directions.

Figure 1: Flagellar bending of a normal (+/+) and a CRIS knock-out sperm (-/-).

As a result, sperm from CRIS knock-out males were only swimming in circles, which impaired directed swimming towards the egg and severely reduced fertility. Thus, we identified CRIS as a new regulator of sperm development, which is crucial for the control of flagellar bending. Unraveling the function of CRIS might contribute to a better knowledge of the causes underlying male infertility.

Publication

Krähling, M., Alvarez, L., Debowski, K., Van, Q., Gunkel, M., Irsen, S., Al-Amoudi, A., Strünker, T., Kremmer, E., Krause, E., Voigt, I., Wörtge, S., Waisman, A., Weyand, I., Seifert, R., Kaupp, U. B. & Wachten, D. (2013) "CRIS- a novel cAMP-binding protein controlling spermiogenesis and the development of flagellar bending" PLoS Genetics, DOI: 10.1371/journal.pgen.1003960