In humans, male and female partners contribute more or less equally to the
infertility problem. In approximately 20% of infertile couples, the concurrence of male and female factors is suggested to be responsible for
infertility. Neither of these factors are known nor is there a model system to prove this assumption. We present such a model system in the mouse, in which the lack of
acrosin in the male and modifications of the zona pellucida (ZP) in the female result in a significant reduction of the fertilization rate in vitro. We generated mice carrying a deletion in the
proline-rich region (PRR) of the
proacrosin gene, resulting in the absence of
proacrosin in the homozygous PRR(-/-) male mouse. Under normal conditions, sperm from the
proacrosin-deficient mice are still capable of ZP penetration and fertilization. In this study, modifications of the ZP of oocytes after superovulation were achieved by treatment with
dimethylsulphoxide or
aroclor-1254 or by in-vitro ageing. It is known that under these conditions, a time-dependent hardening of the ZP occurs. The rates of fertilization in vitro of treated and aged oocytes using sperm from PRR(-/-) mice were found to be significantly reduced when compared with those reached with wild-type sperm. The relevance of the
acrosin status and ZP condition for fertilization success were further substantiated by the finding that the fertilization rate with PRR(-/-) sperm is affected by the thickness of the ZP. Our results demonstrate that the lack of
acrosin in sperm in combination with modifications to the ZP can affect fertility and can be an experimental model for the study of unexplained
infertility in human couples in which both male- and female-derived factors are suggested to be the underlying causes.