Common Questions with Dr. Matt: Can Exposure Impact Fertility?

In this month's blog by Dr. Matt, he will be discussing the impact of mold and mycotoxins on fertility. Read on to learn more about how these toxic microbes can impact both men and women.

Hello again to our TMP blog.  Today’s question is a less of a common question, but more of a common problem that is now getting more attention, which is the role that mold and mycotoxins have in inhibiting fertility.   Declining fertility is becoming a problem with both males and females in the last 50 years. This has become especially clear with the decline of sperm counts in North America, Europe, Australia, and New Zealand by more than 59% (1).  For females, miscarriage rates of increased from 1990 to 2011 by 2% (2).  There seems to be theories for these occurrences such as increased pollution and estrogenic plastics.  One factor that may be playing a role could be mycotoxins, however, there is little to no research on its significance in this question.  However, it is known that exposure to Ochratoxin A (OTA) and/or Zearalenone (ZEA) can affect the fertility of humans.  

OTA is produced by the several members of the Aspergillus and Penicillium genera (3).  In developed countries it is most likely that exposure to these toxins is occurring through the environment (contaminated buildings) and not through food sources (4).  OTA causes damage through multiple different processes such as DNA damage through abduct formation, inhibition of protein synthesis, and apoptosis induction caused by loss of mitochondrial membrane potential (5).  OTA has a relatively long half-life and for some individuals the excretion pattern can be very inconsistent  

Concerning fertility, OTA exposure can negatively affect both male and female fertility.  In males OTA has been shown to have quite detrimental effects on sperm viability and morphology (swollen head, coiled tail, decapitation) (6).  These changes will decrease sperm motility, which will result in lower rates of fertilization.

OTA has also been shown to be unfavorable regarding female fertility. Although there is limited data regarding human cells, there is significant data from other mammalian species.  In sheep, OTA exposure causes an inhibitory effect on oocyte maturation(7).  These findings where support by other studies in porcine, mice, and pigs (8, 9).  OTA at high levels caused changes in the mitochondrial distribution of the cells, which will affect how the cells produce energy.  At lower concentrations levels OTA reduced mitochondrial activity and generated ROS molecules.  Mouse oocytes exhibit a reduced ability to be fertilized by sperm after the oocytes were exposed to OTA (10).  These data indicate that males and females exposed to OTA may have increased difficulty becoming having children.

As stated above OTA is can cause problems with fertility, but ZEA may be even worse.  ZEA is an estrogenic mycotoxin produced by several Fusarium species (11).  ZEA has the capability to bind to the estrogen receptor (ER) and cause it to become activated.  There are many papers showing how ZEA has equal potency to activate ER as Estradiol, so I chose this figure from Krisztet al to illustrate my point.  As you can see in figure 1 ZEA exposure can lead to uterine engorgement, similar to estradiol exposure (12).  Because of this capacity, ZEA is detrimental to both male and female fertility.  

In males ZEA exposure leads to germ cell cytotoxicity.  Some of these cells, which are labeled Leydig cells, are important for forming and maintaining the male reproductive tract.  Exposure to ZEA can decrease the number of cells and lead to deformations (13).  Similar to OTA, ZEA exposure has an adverse effect on spermatogenesis.  Because of ZEA’s estrogenic potency it can lead to males having lower testosterone, which then leads to lower sperm counts (14).  

In females, ZEA exposure is extremely detrimental to both fertility as well as reproductive organ development.  As seen in figure 2, there are multiple different systems that are negatively affected by ZEA exposure in females.  In many different mammals ZEA exposure can lead to accelerated puberty (15, 16).ZEA exposure results in a less oocyte maturation because of downregulation of transcriptional factors(17).  Remember again that figure 1 shows us that ZEA exposure leads to uterine changes, which include uterine weight gain. One other major problem caused by ZEA exposure is associated with the placenta.  Studies have indicated that ZEA exposure can lead to decrease in placental thickness, increase of placental hemorrhage, and a decrease in implantation sites(18, 19).  In regards to fertilization, ZEA exposure decreases the ability of fertilized eggs from forming blastocysts.  

In conclusion, it is really important for both men and women to limit their exposure to both OTA and ZEA.  If they have been exposed then they should consult with a practitioner to help with removal of the toxins out of their body.  They should also consult with an indoor mold specialist (such as the Mold Pros) to investigate and possible treat their living areas.

Resource List

1. H. Levine et al., Temporal trends in sperm count: a systematic review and meta-regression analysis. Hum Reprod Update 23, 646-659 (2017).

2. L.M. Rossen, K. A. Ahrens, A. M. Branum, Trends in Risk of Pregnancy Loss Among US Women, 1990-2011. Paediatr Perinat Epidemiol 32, 19-29 (2018).

3. F. Malir, V. Ostry, A. Pfohl-Leszkowicz, J. Malir, J. Toman, Ochratoxin A: 50Years of Research. Toxins (Basel) 8 (2016).

4. B. Cramer et al., Biomonitoring using dried blood spots: detection of ochratoxin A and its degradation product 2'R-ochratoxinA in blood from coffee drinkers. Mol Nutr Food Res 59, 1837-1843 (2015).

5. Y.Tao et al., Ochratoxin A: Toxicity, oxidative stress and metabolism. Food Chem Toxicol 112, 320-331(2018).

6. D. Chakraborty, R. Verma, Spermatotoxic effect of ochratoxin and its amelioration by Emblica officinalis aqueous extract. Acta Pol Pharm 66, 689-695 (2009).

7. M.E. Dell'Aquila et al., Ochratoxin A affects oocyte maturation and subsequent embryo developmental dynamics in the juvenile sheep model. Mycotoxin Res 37, 23-37 (2021).

8. Y.Lu et al., Comparison of the toxiceffects of different mycotoxins on porcine and mouse oocyte meiosis. PeerJ 6, e5111 (2018).

9. C.H. Huang, F. T. Wang, W. H. Chan, Prevention of ochratoxin A-induced oxidative stress-mediated apoptotic processes and impairment of embryonic development in mouse blastocysts by liquiritigenin. Environ Toxicol 34, 573-584 (2019).

10. F.J. Huang, W. H. Chan, Effects of ochratoxin a on mouse oocyte maturation and fertilization, and apoptosis during fetal development. Environ Toxicol 31,724-735 (2016).

11. A. Zinedine, J. M. Soriano, J. C. Molto, J. Manes, Review on the toxicity, occurrence, metabolism, detoxification, regulations and intake of zearalenone: an oestrogenic mycotoxin. Food Chem Toxicol 45, 1-18 (2007).

12. R. Kriszt et al., Xenoestrogens Ethinyl Estradiol and Zearalenone Cause Precocious Puberty in Female Rats via Central Kisspeptin Signaling. Endocrinology 156, 3996-4007 (2015).

13.          P.Pan et al., Maternal exposure to zearalenone in masculinization window affects the fetal Leydig cell development in rat male fetus. Environ Pollut 263, 114357 (2020).

14. F.A. Gbore, G. N. Egbunike, Testicular and epididymal sperm reserves and sperm production of pubertal boars fed dietary fumonisin B(1). Anim Reprod Sci 105,392-397 (2008).

15. F. Zhao et al., Postweaning exposure to dietary zearalenone, a mycotoxin, promotes premature onset of puberty and disrupts early pregnancy events in female mice. Toxicol Sci 132, 431-442(2013).

16. R.Kriszt et al., A new zearalenone biodegradation strategy using non-pathogenic Rhodococcus pyridinivorans K408strain. PLoS One 7, e43608 (2012).

17. G.L. Zhang et al., Zearalenone exposure impairs ovarian primordial follicle formation via down-regulation of Lhx8expression in vitro. Toxicol Appl Pharmacol 317, 33-40 (2017).

18. K. Kunishige, N. Kawate, T. Inaba, H. Tamada, Exposure to Zearalenone During Early Pregnancy Causes Estrogenic Multitoxic Effects in Mice. Reprod Sci 24, 421-427(2017).

19. R. Li et al., Dietary exposure to mycotoxin zearalenone (ZEA) during post-implantation adversely affects placental development in mice. Reprod Toxicol 85, 42-50 (2019).

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