The Function of Endogenous Platelet Activating Factor (PAF) in Human Sperm

Body: 

by

Slee L. Yi1, Julia M. Robison1, and William E. Roudebush1,2

1University of South Carolina School of Medicine Greenville, 2Fertility Center of the Carolinas, Department of Obstetrics & Gynecology,
Greenville Health System, Greenville, South Carolina

 

Eight to ten million couples are afflicted with infertility in the United States. Infertility can be caused by a number of factors. Not only females but also males can have problems with infertility. Male infertility is the primary culprit in ~25% of these couples, and is a factor in additional 20% of these couples. There are several prerequisites that must be met for male fertility. Defects in any of these will result in infertility.1

Platelet Activating Factor

Platelet-activating factor, commonly known as PAF, is a phospholipid involved in a number of biological activities. PAF was first discovered and studied in rabbits over thirty years ago.2 It is known to be present in several mammalian species including mice, bulls, boars, and even humans.1,3-5 Since its discovery, PAF has been found to play a significant role in reproductive physiology.1

Research shows that PAF plays a very important role in sperm motility. It does this through binding to PAF receptors found in the sperm membrane.  Reports indicate that PAF receptors exist at the midpiece (neck) and the equatorial (head) regions of the sperm. Binding at these locations leads to an increase in fertility rate. Conversely, when these receptors are abnormal or appear at abnormal locations, fertility is compromised.1,6

During the last few years, scientists have discovered different amounts of PAF and PAF receptors in motile and non-motile sperm. Studies have found that motile sperm contain a greater number of PAF receptors than do non-motile sperm.  Interestingly as well, the actual PAF concentration in motile sperm appears to be less compared to non-motile sperm. This indicates that non-motile sperm contain more PAF than motile sperm because they are not able to use it. Motile sperm shows less PAF content because these cells are using it.1,7 Fertility may be further compromised in the presence of PAF antagonists.  These are substances that compete against PAF at the receptor site, which causes a decrease in PAF binding and can resuls in infertility. Although the exact mechanism for this is unclear, its importance is substantial. 1,8-10

The active form of PAF is produced inside the male sperm cell through a cycle of reactions. The enzyme responsible for synthesizing active PAF is also found in the sperm cell itself.1,11 However, there are enzymes that disable PAF by converting it into an inactive form.1,12These disabling agents are present in seminal fluid.13 The process therefore requires sperm to be separated from the seminal fluid in order for PAF to become active and cause increased sperm motility. This separation occurs when sperm is ejaculated – typically into the vagina, where it will swim away from the fluid and enter the uterus. Once sperm is separated from the seminal fluid, PAF can be synthesized and subsequently bind to its receptors on the sperm cell membrane. Once the sperm responds to PAF, its motility dramatically increases, and it becomes ready to fertilize the egg.14 This process is called capacitation. As expected, sperm cells that have not yet capacitated are found to contain lower levels of PAF.1,12 That is because, as explained, the seminal fluid contains substances which prevent active PAF from being synthesized. On the other hand, capacitated sperm cells are found to contain higher levels of PAF. When active PAF is present in the sperm cell and is able to appropriately bind to its receptors, it improves interactions between sperm and egg, and positively affects pregnancy outcomes.1 Determining the active PAF content and its interaction with receptors could potentially be a beneficial diagnostic tool for male infertility. Further research should be conducted to better understand PAF and how PAF could possibly be useful in clinical applications such as in vitro fertilization (IVF) in the near future.1,15

 

References

1. Roudebush WE. Seminal platelet-activating factor. Semin Throm Hemost 2007;33:69-74

2. Benveniste J, Henson PM, Cochrane CG. Leukocyte dependent histamine release from rabbit platelets: the role of Ig-E, basophils, and platelet-activating factor. J Exp Med 1972;136:1356–1376
3. Parks JE, Hough S, Elrod C. PAF activity in bovine sperm. Biol Reprod 1990;43:806–811
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4. Minhas BS, Kumar R, Ricker DD, Robertson JL, Dodson MG. The presence of platelet activating factor-like activity in human sperm. Fertil Steril 1991;55:372–376
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5. Mook JL, Diehl JR, Mathur RS, Roudebush WE. Presence of platelet-activating factor in porcine sperm and uterine fluid. Theriogenology 1998;49:351
6. Harper MJK. Platelet activating factor: a paracrine factor in 
preimplantation stages of development? Biol Reprod 1989; 40: 907–913

7. Purnell ET, Roudebush WE. Platelet-activating factor activity levels (ligand and receptor transcript content in sperm: motile versus nonmotile. In: Proceedings of the VIIth International Congress of Andrology. Montreal, Quebec: Andrology in the 21st; 2001:71-76.

8. Reinhardt JC, Cui X, Roudebush WE. Immunofluorescent evidence of the platelet-activating factor receptor on human spermatozoa. Fertil Steril 1999;71:941–942
9. Roudebush WE, Ito C, Purnell E, Cui X. Presence of platelet-activating factor and its receptor in baboon (Papio spp) spermatozoa. Int J Primatol 1999;20:273–280
10. Roudebush WE, Wild MD, Maguire EH. Platelet-activating factor receptor expression in human sperm: differences in mRNA content and protein distribution between normal and abnormal sperm. Fertil Steril 2000;73:967–971

11. Bennet PJ, Moatti JP, Mansat A, et al. Evidence for the activation of phospholipases during acrosome reaction of human sperm elicited by calcium ionophore A23187. Biochim Biophys Acta 1987;919:255–265

12.  Letendre ED, Miron P, Roberts KD, Langlais J. Platelet- activating factor acetylhydrolase in seminal plasma. Fertil Steril 1992;57:193–198

13. Gujarati VR, Naukam RJ, RamaSastry BV. Enzymatic deacetylation and acetylation of ether phospholipids related to platelet-activating factor in human semen with short and long liquefaction times. Ann N Y Acad Sci, 1987, 513:583–585.

14. Davis BK. Timing of fertilization in mammals: Sperm cholesterol/phospholipid radio as a determinant of the capacitation interval. Proceedings National Academy of Sciences of the United States of America. 1981, 78:7560-7564.

15. Toledo AA, Mitchell-Leef D, Elsner CW, Slayden SM, Roudebush WE. Fertilization potential of human sperm is correlated with endogenous platelet-activating factor content. J Assist Reprod Genet 2003; 20:192–195.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Blackboard with MALE INFERTILITY on it

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