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DISTINGUISHING BETWEEN FERTILIZATION FAILURE AND EARLY PREGNANCY LOSS WHEN IDENTIFYING MALE-MEDIATED ADVERSE PREGNANCY OUTCOMES
Citation:
PERREAULT, S D. DISTINGUISHING BETWEEN FERTILIZATION FAILURE AND EARLY PREGNANCY LOSS WHEN IDENTIFYING MALE-MEDIATED ADVERSE PREGNANCY OUTCOMES. Advances in Experimental Medicine and Biology. Springer, New York, NY, 518:189-198, (2003).
Description:
Successful reproduction depends upon the precise orchestration of many physiological processes. With respect to male reproductive performance, normal copulatory behavior and ejaculatory function are required to insure that semen is deposited in the female tract. Then, a sufficient number of sperm must reach the site of fertilization at the optimal time for the oocyte to be fertilized, and those sperm that reach the oocyte must be capable of fertilizing the egg (binding and penetrating the zona pellucida and fusing with the oolemma). Finally, the fused spermatozoon must be intact genetically in order to support normal embryonic and postnatal development. Environmental exposures may impact any of these events, resulting in infertility. When embryos are lost before implantation, it is difficult, if not impossible, at least in humans, to distinguish between infertility due to very early embryo death and that due to failed fertilization. Why does this distinction matter? Toxicologists testing various types of therapeutic drugs need to identify potential side effects on reproduction, including any deficits in spermatozoa that could affect either fertility or early embryonic development. Also, reproductive and developmental toxicology risk assessors in Federal Agencies such as the US EPA, FDA and USDA, need information about the modes of action of reproductive toxicants identified in animal test species in order to extrapolate potential risks to humans. For example, if a chemical alters fertility in rats, it is important to know the affected sex, and to characterize the mode and mechanism of action to determine if that chemical is likely to produce the same effect in humans. Acrylamide is a reactive chemical that affects both reproductive physiology and the genetic integrity of spermatozoa and is discussed here to provide a case study. By using a modification of the standard dominant lethal test design, the nature of its effects on both sperm physiology and genetic integrity can be distinguished.