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.
|Heat||Low sperm count, motility, morphology|
|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:
|20-50||Azoospermia (20-60%)||6-8 months|
|50-100||Azoospermia (50-80%)||8-14 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 antibiotics. Little is known of the effect of antibiotics on human fertility. However, 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.
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