Nov 4, 2022

Jan Friberg M.D., Ph.D.

In natural fertilization only a very selected number of spermatozoa reach the oocyte to succeed with fertilization. It appears that the female is able to select the particular sperm that will fertilize the egg – a process known as mediated sperm selection or cryptic female choice (CFC). This phenomenon has been known to occur ubiquitously among fish species and marine mussels where chemoattractants selectively change sperm swimming behavior. In the last 1- 2 years, CFC has been proven to occur in animals and even in humans and mediated by a complex network of interacting male and female genes.

                The genetic control follows the same biological mechanisms that prevent interspecies reproduction i.e that monkey sperm can not fertilize a human egg. It is mediated after mating and is expressed in the cervical mucus, uterine fluid, tubal secretion and is in action all the  way up to and through the fertilization. Genes control the secretion of molecules that are dispersed into the female genital fluids and affects the ability of sperm to proceed through the female genital tract. It may be at least one of the factors responsible for the fact that out of the millions of sperm in the ejaculate only about 50 – 100 sperm reach the fertilization site at the tip of the oviduct after intercourse. It appears presently to be mostly controlled through the tissue type (Human Leucocyte Antigens, HLA)  system, but  certain immunoglobulins needs to have structural similarity between male and females to allow fertilization to occur. The complexity of the system has been revealed in the last year when even proteins and surface carbohydrates (glycans) have been shown to affect compatibility between males and females. This is caused by a females immune response against certain mismatched sperm surface glycans. Of importance is that this “compatibility verification process”  of gamets occurs before there is a physical contact between the sperm and the oocyte and is mediated by chemical signals secreted by the female reproductive tract. This gamets mediated mate choice may be to “evaluate” the immunogenetic compatibility of the reproductive partner prior to gamete fusion. Currently about 15 genes have been identified that mediate physical interaction between sperm and egg and found to be essential for fertilization. The identity of interacting male and female genes for this incompatibilities are still largely unclear and  in humans only one directly sperm-oocyte interacting binding gene pair has so far been identified. This means that the female reproductive tract can identify compatible sperm based on specific gamete surface markers. Consequently certain sperm types can have a high reproductive success with certain females but can have a much lower reproductive success with other females.

                In humans it has recently been shown that follicular fluid highly selectively attracts the sperm of specific males over others and different female reproductive secretions is strongly dependent on certain male-female combinations. In addition to affecting fertilization the compatibility of gametes also appears to affect embryo survival and development of the fetus.

                In current medical practice infertility is thought to be caused by the development of special pathological factors in both men and women. However, it now seems to also involve a degree of specific selection between the sperm and the egg. This explains the common situation when the fertility investigation doesn’t detect any reason for the infertility. One way to overcome this situation is to resort to IVF with ICSI. It may also shed some light on why couples with unexplained infertility of more than 3 years duration have as poor natural pregnancy rate as couples with a pronounced fertility factor and IVF with ICSI is also recommended for this group.

                This increasing knowledge of the level incompatibility of gamets from reproductive couples will deepen our understanding of these evolutionary mechanisms of sperm selection and can pave the way towards a more inclusive view  of infertility and open novel possibilities for the development of more personalized infertility diagnosis and treatments.