Reproductive toxicity may occur as a result of environmental exposure or occupational exposure (two recent examples of occupational reproductive toxicity have been reported with battery plant workers exposed to dibromochloropropane, a refrigerant, soil fumigant, and aerosol propellant, in Bulgaria and lead miners in Missouri who have shown a decreased child birth rate compared to the surrounding population).

Reproductive toxicity may occur during any stage from gametogenesis to implantation.  The toxicant may mimic natural compounds (i.e. environmental œstrogens) or they may alkylate DNA resulting not in a cell transformation as with cancer but a mutation that affects only the germ cell.  RECALL that in males, spermatogenesis does not begin until puberty but then continues throughout the reproductive life of the male.  Therefore, germ cell (spermatocyte) mutation may occur during any point in the life of the man.  Females are born with the set number of oocytes, which gradually die off during the reproductive life of the female.  Therefore, oocyte synthesis cannot be interfered with. However, oocyte maturation may be a possible target of toxicant action.

Therefore toxicant action may reflect chemical damage resulting in decreased viability of the germ cell (spermatocyte or oocyte) either through hormonal or alkylating effects through actions that interfere with spermatogenesis, Sertoli cell function (nutrition of the developing spermatocyte), or Leydig cell function (spermatocyte maturation, testosterone dependent) in the male or oocyte maturation, and œstrogen-dependent changes in oviductal, uterine, cervical, or vaginal structure or function in the female.  (NOTE that testes and ovaries possess limited cytochrome P₄₅₀ activity to aid in the metabolism of some compounds.)

Some compounds may produce reproductive toxicity that are, strictly speaking, teratogenic (recall that teratogenic toxicity occurs in the offspring of mothers exposed to certain toxicants).  These effects in the offspring are specifically reproductive in nature and the progeny may be normal with the exception of these effects.  Examples of agents that produce this type of toxicity include

Methoxychlor (an insecticide similar to DDT but less persistent in the environment) -- will decrease fertility in both male and female progeny of an exposed mother.

Dimethylbenzathracene & Benzo(a)pyrene (carcinogenic compounds) -- exposure to the mother will cause gonadal hyperplasia and decreased fertility in the offspring.

Cyanoketone -- Offspring of exposed mothers will demonstrate altered œstrus cycles.

Diethylstilbœstrol (DES) -- Mother exposed to DES will produce female progeny that may develop endometrial carcinoma and males that exhibit decreased sperm count and motility and an increase in the number of abnormally developed sperm.

Triazine/Hydrazine Herbicides -- These agents may act to inhibit androgen synthesis.  If this occurs in utero, then testosterone synthesis is inhibited, thus inhibiting sexual differentiation during development, leading to hermaphroditism (recall that all embryoes are female and it is the gene for testicular development and subsequent testosterone production that determines the development of the male offspring -- these herbicides, or any other anti-androgen, will inhibit this testosterone effect). Consequently, a child is born with improper genitalia and an inability to reproduce.

Environmental Œstrogens -- in utero exposure may cause minisation of the male fetus (even with normal testes and sperm counts)
 

Reproductive Toxicants that exhibit their effect in the subject exposed include the following:
Triazine/Hydrazine Herbicides -- inhibit androgen synthesis as described above.  These agents will interfere with androgen-dependent processes in spermatocyte development and maturation, causing a decrease in fertility of the male.

Environmental Œstrogens -- in males, these compounds will alter the bound:free ratio of androgens and cause feminisation of mature males.  In females they will exert œstrogenic or anti-œstrogenic action (partial agonist/antagonist activity) that would disrupt normal menstrual or œstrus cycles.  Examples of environmental œstrogens include

Chlorinated insecticides -- chlordane, kepone, DDT

Polychlorinated Biphenyls -- (Arochlor®) -- these are high temperature dielectrics (compounds that will hold but not conduct an electrical current) that are used for electrical wires, motors, transformers, capacitors, and heat exchange fluids, as well as plasticisers, coatings, fillers, adhesives, paints, inks, and in duplicating papers.

Polycyclic Aromatic Hydrocarbons (PAHs) -- from automobile exhaust or cigarette smoke.

Naturally Occurring -- fungi (mycotoxins) -- zearalenone, -- plants -- coumestrol, genistein, found in over 40 species of flowers, including the Texas Blue Bonnet
 

Gossypol  -- is an anti-androgen present in cotton seed.  It and its action was discovered when it was noted that workers in a Chinese cotton mill had a reduced birth rate in their families.  It was discovered that the active constituent, gossypol, decreased sperm production.  It has bee investigated for use as a male contraceptive.

Other agents that have either laboratory or clinical reports of interfering with reproduction include the following:

Heavy Metals --
Male -- Aluminium, Arsenic, Boron, Cadmium, Cobalt, Lead, Magnesium, Molybdenum, Nickel, Silver, and Uranium

Female -- Arsenic, Lead, Lithium, Magnesium, Molybdenum, Nickel, Selenium, and Thallium

Insecticides --
Male -- lindane, carbaryl, aldrin, dieldrin, chlordane
Female -- lindane, carbaryl, aldrin, dieldrin, parathion, mirex
Herbicides --
Male -- 2,4-Dichlorophenoxyacetic acid; 2,4-Trichlorophenoxyacetic acid; diquat; and paraquat

Females -- 2,4-D; 2,4-T

Fungicides -- Male and Female -- cineb, maneb

Industrial Toxicants -- Male and Female -- vinyl chloride, solvents (benzene, toluene, xylene, chloroform)

Consumer Products --

Male -- flame retardants (2,3 dibromopropyl phosphate); plasticisers (phthalate esters)
Female -- flame retardants (polybrominated biphenyls or PBBs); plasticizers (phthalate esters)
 
Miscellaneous -- Male and Female -- ethanol, marijuana