Environmental and Occupational Hazards and Male infertility

 

Environmental agents can adversely affect germ cell development at many different stages from proliferating spermatogonia to mature spermatozoa.Although they have been shown to affect male reproductive function in animals, large difference in reproductive function between species limit extrapolation to human. Human data are often conflicting.

Possible different toxic effects include cell death, sublethal cell damage or genetic change. Cell dying within the epithelium may do so by necrosis or apoptosis (or programmed cell death). Recent evidence suggest that apoptosis is the major mechanism of action of some testicular toxins or adverse physiological conditions such as gonadotropins deprivation. Nonlethal germ cell damage will be repaired or leave permanent effect on structure or function of mature spermatozoa, including possibility of genetic defects.

Occupational exposure to sex steroids such as estrogens, can exert negative biofeedback on FSH secretion and result in decreased sperm production, sexual dysfunction, gynecomastia and hypogonadotropic hypogonadism, and potentially to cryptorchidism and testicular cancer). Prenatal exposure to estrogens could potentially inhibit fetal gonadotropins secretion and reduce Sertoli cell proliferation. Several compounds are known to have antiandrogenic activity (9,10-Dihydrophenanthrene, Linuron, Vincozolin, DDT/DDE, and Flutamide)

Direct testicular toxicity may potentially affect separate cell types within testis with subsequent affect on spermatogenesis and steroidogenesis in general. No specific human Sertoli cell toxins have yet been established. Iionizing radiation and alkylating agents ( e.g. nitrogen mustard, vincristine, procarbazine, prednisone) were found to have most profiund toxicity to human germ cells . The most sensitive cells are spermatogonia. Nonproliferating spermatogonia A0 , if destructed, leads to irreversible spermatogenic damage, while proliferating spermatogonia can be replaced from stem cell reserves.

Although persistent mutation in stem cells DNA can lead to persistent genetic changes in sperm, such chromosome defects did not translated to excess congenital malformation or carcinogenesis among offsprings of male cancer treatment survivors.

Adrenolytic drugs such as guanethidine or methoxamine lead to stasis of sperm in the epididymis. Gossipol affects epididymal epithelium and interfere with epididymal fluid excretion.

ExposurePossible Effects
HeatLow sperm count, motility, morphology
Ionizing RadiationAzoospermia
Nonionizing radiationMicrowavesElectromagnetic fields Low sperm count and motility(temporary)Low sperm count and motility
Metals Lead ,Mercury, Cadmium, Boron Sperm morphology, count, motility, semen volume 
EstrogensSynthetic (Diethylstilbestrol)Dietary( lignans, mycoestrogens , phytoestrogens ) Hormone levelsGynecomastia, libido, impotenceLow sperm count
PesticidesDibromochlorpropane , Ethylene dibromide, Chlordecone Sperm morphology, count, motilityHormonal imbalance
Solvents Carbon disulfide, Glycol ethers  Sperm morphology, count, impotenceHormonal imbalance

 

Effect of ionizing radiation:

Dose (cGy)EffectReversibility
15-20Little effect-
20-50Azoospermia (20-60%) 6-8 months
50-100Azoospermia (50-80%)8-14 months
100-200Azoospermia(90-100%)12-24 months
>200Azoospermia(100%)>24 months

 

Proliferating spermatogonia is the most sensitive element. Chromosomal damage is observed in germ cells that survive radiation

  Cigarette smoking is associated with modest reduction in sperm concentration(13-17%), motility and morphology. Smoking may alter hormone levels in males. Despite these findings, there is no data to confirm a statistically significant reduction in male fertility in smokers. Interestingly, in-vitro studies suggested that Nicotine may not be responsible for the harmful effect of cigarette smoke on the sperm kinetic parameters.

Limited studies suggested smoking to be mutagenic to human spermatozoa and lead to cancer, birth defect and genetic diseases in offspring.

Excessive alcohol intake is associated with direct testicular toxicity.

Anabolic Steroids have been used by athletes to improve strength and performance for many years Among other side effects, anabolic steroids induce hypogonadotropic hypogonadism with associated azoospermia or oligospermia, abnormal sperm morphology, motility and testicular atrophy. These effects result from negative feedback of androgen on hypothalamo-pituitary axis and possible local suppressive effect of excess androgens on the testis. The management of cases with infertility secondary to anabolic steroid abuse is controversial and range from watchful waiting with spontaneous recovery of spermatogenesis to hormonal intervention. The spontaneous recovery of spermatogenesis has been documented with high variability. Eventual successful return of fertility may be suspected by slow recovery of gonadotropins (FSH and LH). The hormonal treatment of hypogonadal hypogonadism with intramuscular injection of HCG and HMG and subsequent maintenance HCG injection has been proposed, if no improvement occurs longer than 6-24 months after discontinuation of steroids.

 Use of antibioticsLittle is known of the effect of antibiotics on human fertilityHowever, most major classes of antibiotics were found to have effect on fertility in animal studies. The common manifestations are spermatogenic arrest and impaired sperm motility and morphology. Examples of evaluated drugs are nitrofurantoin, erythromycin, gentamycin,neomycin,tetracyclin,sulfasalazine,penicillin G, ampicillin.

Limited human studies addresses the effect of Recreational drugs on fertility. Sperm concentration and motility were found to be low in cocaine and marijuana addicts.

 

Selected Bibliography

 
  1. Brinkworth MH, Handelsman DJ. Occupational and environmental Influences on Male Infertility. In: Nieschlag E., Behre HM, editors Andrology: Male Reproductive Health and Dysfunction. Springer 1997, chapter 13, 241-253
  2. Baranski B. Effect of workplace on fertility and related reproductive outcomes. Environmental Health Perspect 1993;101:81-90
  3. Bonde JP, Giwercman A. Occupational hazards to male fecundity. Reprod Med. Rev 1995;4:59-73
  4. Barlow SM, Dayan AD, Powell CJ. Reproductive Hazards at Work. In: Raffle PAB, Adams PH, Baxter PJ, Lee WR, editors. Hunter's diseases of occupation. Arnold, London, 1995; 723-742.
  5. Tas S, Lauwerys R., Lison D. Occupational Hazards for Male Reproductive System. Critical Rev Toxicol 1996;26(2):261-307
  6. Vine MF, Tse C-K., Hu P-C., Truong KY. Cigarette smoking and semen quality. Fertil Steril 1996;65:835-842
  7. Sofikitis N., Miyagawa I., Dimitriadis D., Zavos P., Sikka S., Hellstrom W. Effects of smoking on testicular function, semen quality and sperm fertilizing capacity. J Urol 1995;154:1030-1034
  8. Fraga CG., Motchnik PA, Wyrobek AJ., Rempel DM.,Ames BN. Smoking and low antioxidant levels increase oxidative damage to sperm DNA. Mutation res 1996;351:199-203
  9. Dunphy BC, Barratt CL, von Tongelen BP, Cooke ID. Male sigarette smoking and fecundity in couples attending an infertility clinic. Andrologia 1991;23(3):223-225.
  10. Barroso-Moquel R., Mendez-Armenta M., Villeda-Hernandez J. Testicular lesions by chronic administration of cocaine in rats. J Applied Toxicol 1994;14(1):37-41
  11. Feichtinger W. Environmental factors and fertility. Hum Reprod 1991; 6(8):1170-1175
  12. Kolodny RD, Masters MH, Kolodner RM, Toro G. Depression of plasma testosterone after chronic intensive marijuana use. N Engl J med 1974;290:872
  13. Little J., Vainio H. Mutagenic lifestyles? A review of evidence of association betwrrn germ-cell mutations in human and smoking, alcohol consumption and use of 'recreational'drugs. Mut res 1994;331:131-151
  14. Cheek AO., McLachlan JA. Environmental hormones and the male reproductive system. J Androl 1998;19:5-10
  15. Yelian FD. Sacco AG. Ginsburg KA. Doerr PA. Armant DR. The effects of in vitro cocaine exposure on human sperm motility, intracellular calcium, and oocyte penetration. Fertility & Sterility1994;. 61(5):915-21
  16. Meistrich ML, Van Beek M. E.A.B. Radiation sensitivity of the Human testis. Advances in Radiation Biology 1990;14:227-268
  17. Hansen PV., Trykker H., Svennekjaer IL, Hvolby J. Long- term recovery of spermatogenesis after radiotherapy in patients with testicular cancer. Rad Oncol 1990;18:117-125.

 

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