Over the years, researchers have searched for the elusive marker of male fecundity (the ability to father children). As with most biological entities, the more it is studied the more complex the system becomes. Basically, the sperm cell has a single mission: inject the male genome to the egg cytoplasm. The sperm cell design is sleek and mission oriented. The chromatin is packed tightly in protamines ready for transport. Not unlike one's clothes in a suitcase in the belly of a jetliner ready for a journey, the chromatin is not readily available for inspection or assessment. No protein synthesis or cell replication will take place in the mature sperm so these biochemical processes cannot readily be assessed. The acrosomal cap contains the hyaluronidase and acrosin to digest the cumulus and zona for delivery of the payload. The mid-piece contains mitochondria to power the motility engine and other functions of this specialized cell. The tail or flagella must propel the cell through several environments. Assessment of the ejaculate to determine the fecundity of the individual requires a basic understanding of the spermatozoa and semen function. It appears that semen provides a nutrient rich protective environment to get the sperm to the awaiting cervix of the female. There are over 300 components of semen, the importance of only a few of these is understood. Fructose from the seminal vesicles is sperm's favorite sugar. Zinc from the prostate is important in the eventual acrosome reaction and chromatin dispersion. The buffering basic pH protects the sperm cells from the acidic environment of the vagina. While seminal plasma plays a vital role in the normal reproductive scenario, assisted reproductive technologies (ART) have shown that seminal plasma is not essential for fertilization. The business of spermatozoa is a numbers game. According to the World Health Organization the normal ejaculate has at least 40 million sperm.[1.] Many ejaculates have hundreds of millions. For a normal reproductive scenario (without ART), there are some basic requirements of a sperm. It must be motile, probably progressively motile (defined as swimming a distance of its overall length in one second). It must have an oval shaped head. This is probably for several reasons. First, this head design allows for the progressive motility of being pushed by the tail. Second, an oval shaped head suggests a normal acrosomal cap that will allow penetration of the egg. Third, there is some research to suggest that an abnormal shaped head may mean abnormal chromatin. [2.] The numbers game requires millions of sperm. A sperm may be perfect in every way, and yet may not be in the portion of the ejaculate that bathes the cervical os, and thus never gets a chance to demonstrate its progressive motility, outstanding genetics, etc. Millions are left behind at the cervix. Much of the transport through the cervix is dependent on progressive motility. More are lost along the uterus and fallopian tubes. Muscular contractions and beating cilia, along with sperm's own motility, bring some sperm forward while others are lost. This is not a race, as the sperm that get there first (close to the egg) sacrifice their lives, releasing hyaluronidase to disperse the cumulus so that the one of the sperm can park up along side the egg, and release acrosin at just the right time to allow penetration. Once inside, the chromatin has to have been packed right for the development of the male pronuceli. All of this with the great expectation that Ms. Egg has done her part correctly. From the above description, it is very apparent that there are numerous components and functions which can fail causing fertility failure. Short of a live birth, the chance of having a single biomarker of all aspects of male fecundity combined is impossible. To date, however, there are several biomarkers to assess the key steps above. Andrology labs assess sperm number, sperm motility, and morphology. These have been basic to semen analyses for 50 years, although the methods have improved in both speed and precision. Development of new biomarkers is being attempted to assess other key steps of the life and function of the spermatozoa. The leading edges of biomarker male fecundity research are assessing sperm chromatin and sperm-egg interaction. Obviously there can be millions and millions of sperm that look great and swim perfectly, but if none can produce a viable male pronucleus, it was a worthless journey. The work of the reproductive toxicologist is to identify chemicals or physical agents which may disrupt this male reproductive function.
Steven M. Shcrader, Chief of REproductive Health Assessment Section, National Institute for Occupational Safety and Health, 4676 Columbia Parkway, Cincinnati, OH 45226, USA