Isoflavones from Soy Consumption and the Effect on Sperm Quality Leah Cody, Adoree Faul, and Madison Tuggle

IntroductionMale infertility is increasing1. Within couples it is estimated male factor infertility accounts for over 50% of infertility cases1. Recently, diet has been researched as a factor contributing to male infertility1. Soy consumption is also increasing, and some studies have looked at soy’s potential impact on male reproductive health.

Soy consumption has been targeted for research because it is the largest dietary source of isoflavones2,3,9. Isoflavones are phytoestrogens. There are many hypotheses that phytoestrogens are EDCs that affect estrogen receptors (ERs) and impact reproductive health 1,2,3,4,5,6,7,8. This research poster evaluates studies that have looked at the impact of soy consumption, focusing on soy’s isoflavones levels – specifically DAI and GEN - and the influence on male infertility.

Related Nutrients

Related Nutrients

There are two types of isoflavones found in soy-based foods: GEN and DAI2,3,9. They exist as biologically inactive beta-D-glycosides2,9. After digestion, they are hydrolyzed into their active form and absorbed in the upper small intestine2,9. As isoflavones, GEN and DAI bind to ERs leading to a series of events mimicking the activity of estrogen2,3,6,7. DAI and GEN exist in a number of soy based foods found in the American diet2,11. Soy can be found in vegetable broth, teriyaki sauce, energy bars, deli meats and even hamburgers11. They also exist in tofu, tempeh and other meat substitutes2,4,11. Many foods are also made with soy flour or soy protein isolate meaning the general population may be consuming much more soy than they realize2,4. Not all sources of soy are necessarily equivalent in the amount of GEN and DAI they contain2. Figure 3 compares GEN and DAI concentrations in different soy-based foods found in Western and Asian diets2. The soy isoflavones found in soybeans versus soy protein isolate are different where soybeans have their source of soy intact and more bioactive2,9. Isoflavones supplements also differ from soy proteins by not yielding all of the advantages found in soy2,5. With all the variability found in different soy products, making scientific conclusions regarding soy’s impact is challenging.

Physiological AspectsIsoflavones have a molecular shape allowing them to bind to ERs in the body giving them estrogen like effects3. Figure 1 compares the molecular shapes. The ability of isoflavones to bind to an estrogen receptor when estrogen is not needed is what makes them EDCs2. When isoflavones bind to ERs they can potentially alter transcription of hormones by acting as a response element causing fewer sex hormones to be transcribed2. They can affect the cell membrane ERs leading to nitric oxide release, calcium flux, and activation of different kinase signaling pathways2.

The interference of isoflavones can result in disruptions of synthesis, secretion, transport, metabolism, and binding abilities of sex hormones due to altered transcription rate, kinase signaling pathways, and substrate concentration2. This leads to a sex hormone imbalance causing a reduction in development and impairment of the reproductive system2.

Figure 2 shows how higher levels of estrogen prevent spermatogenesis10. As estrogen levels increase, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) decrease10. FSH is responsible for stimulating Sertoli cells in the testes which initiate spermatogenesis. LH affects Leydig cells in the testes which produce testosterone, while also stimulating Sertoli cells10. Without FSH and LH at appropriate levels, spermatogenesis will decrease, leading to a decrease in the creation of sperm10. It is theorized that isoflavones mimicking estrogen may be why soy-based foods lead to “feminizing” effects such as reduced semen quality.2,3,4,5,7

ApplicationsDue to the research indicating a negative changes in sperm count and sperm concentration related to isoflavones in soy-based foods, men trying to conceive may choose to avoid soy4,6,7. Higher sperm concentration and count does not correlate directly to improved fertility1,2,3. It is important for men who avoid soy to know what is in the food they are consuming because it is commonly found in processed foods as well as meat alternatives2,3,4,11. There is not enough evidence to support that men of a reproductive age should take soy out of their diet to reduce chances of becoming infertile1,2,3,5. In one case study soy was found to improve fertility in a man who lacked proper reproductive hormones12.

Objectives• To specifically look at the effects of isoflavones in

soy-based food on male sperm quality.• To determine the effect of isoflavones in soy-based

foods on male reproductive ability. • To convey the mixed findings in research on soy

based-food related to male sperm quality.

Figure 1: Molecular Shape of Estrogen compared to GEN and DAI

Estrogen

Daidzein

Genistein

Conclusion and Recommendations Male infertility has been a growing issue in American couples which has led researchers to question dietary impacts on male reproductive health1,2,3.

There is no direct correlation between soy consumption and male infertility, but there are studies proving that isoflavones impact parameters related to sperm quality4,6,7,9. Isoflavones molecular shapes closely resemble estrogen giving them the ability to bind to ERs in the human body2,3,6,7. This results in a number of disruptions in hormonal signaling pathways related to spermatogenesis2,3,6,7.

In order to conclude that men seeking optimal fertile health should avoid all soy products, more studies researching isoflavones and their direct influence are needed.

Spring 2016

AbstractMale infertility and soy consumption are increasing in the Western world 1,2,3. Researchers have theorized that there is a connection between the isoflavones daidzein (DAI) and genistein (GEN) – found in soy-based foods – and male infertility 2,4,5,6. Research has shown that isoflavones are endocrine disrupting chemicals (EDCs) and act in a similar manner to estrogen and affects spermatogenesis 2,3,4,5,7. However, while there is some evidence that isoflavones related to soy consumption affect sperm quality parameters – especially sperm concentration – there is no evidence that this affects overall fertility in men 2,4,6,7,8. The consumption of isoflavones found in soy will not drastically impact male fertility.

Hypothalamus

Anterior Pituitary

GnRH

Inhibin

Testosterone

Figure 2: The Effects of Estrogen on Spermatogensis10

Sertoli Cells Leydig Cells

LHFSH

Stimulates Spermatogenesis Testosterone

Inhibits LHInhibits FSH

Estrogen Estrogen

FSH – follicle–stimulating hormoneLH – lutenizing hormoneGnRH – gonadotropin-releasing hormone

Soy Beans, Raw

Soy Beans, Cooked

Temph Tofu Soy Meal Soy Flour Soy Protein Isolate

Soy Milk0

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DAI (mg/100g)GEN (mg/100g)

Asian

Figure 3: DAI and GEN Concentration in Common Western and Asian Foods2

Western

1. Minguez-Alarcon L., Afeiche M.C., Chiu Y.H., Vanegas J.C., Williams P.L., Tanrikut C. et al. Male soy food intake was not associated with in vitro fertilization outcomes among couples attending a fertility center. Andrology. 2015; 3(4): 702-708. doi. 1111/andr.12046. 2. Cederroth C., Zimmermann C., Nef S. Soy phytoestrogens and their impact on reproductive health. Molecular and Cellular Endocrinology. 2012; 355(2): 190-200. doi: 10.1016/j.mce.2011.05.049 3.Hamilton-Reeves J., Vazquez G., Duval S., Phipps W., Kurzer M, Messina M. Clinical studies show no effects of soy protein or isoflavones on reproductive hormones in men: Results of a meta-analysis. Fertility and Sterility. 2010; 94 (3): 997-1007. doi: 10.1016/j.fertnstert.2009.04.038. 4.Chavarro J.E., Toth T.L., Sadio S.M., Hauser R. Soy food and isoflavone intake in relation to semen quality parameters among men from an infertility clinic. Human Reproduction. 2008; 23 (11): 2584-2590. doi: 10.1093/humrep/den243. 5.Beaton L.K., McVeigh B.L., Dillingham B.L., Lampe J.W., Duncan A.M. Soy protein isolates of varying isoflavones content do not adversely affect semen quality in healthy young men. Fertility and Sterility: 2010; 94(5): 1717-1722. http://www.sciencedirect.com/science/article/pii/S0015028209035948. 6.Xia Y., Chen M., Zhu P. Urinary phytoestrogen levels related to idiopathic male infertility in chinese men. Environment International. 2013; 59: 161-167. doi: 10.1016/j.envint.2013.06.009. 7.Mumford S., Kim S., Chen Z., Barr D., Louis G. Urinary phytoestrogens are associated with subtle indicators of semen quality among male partners of couples desiring pregnancy. Journal of Nutrition. 2015; 145 (11): 2535-2541. doi: 10.3945/jn.115.214973. 8.Dillingham B.L., McVeigh B., Lampe J. Soy protein isolates of varying isoflavone content exert minor effects on serum reproductive hormones in healthy young men. The Journal of Nutrition. 2005; 135(3): 584-591. http://jn.nutrition.org/content/135/3/584.long. 9.R.A. King, J.L. Broadbent, R.J. Head. Absorption and excretion of the soy isoflavone genistein in rats. Journal of Nutrition, 1996; 126 (1): 176–182. http://jn.nutrition.org/content/126/1/176.long. 10.Widmaier E.P., Raff H., Strang K.T. Vander’s Human Physiology: the Mechanism of Body Function. 10th ed. Boston: McGraw-Hill; 2016. 11.A Guide to Foods Rich in Soy. University of California San Francisco. https://www.ucsfhealth.org/education/a_guide_to_foods_rich_in_soy/. Accessed April 5, 2016. 12.Casini M.L., Gerli S., Unfer V. An infertile couple suffering from oligospermia by partial sperm maturation arrest: Can phytoestrogens play a therapeutic role? A case report study. Gynecological Endocrinology. 2006; 22: 399-401.

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