Male reprotoxicity and endocrine disruption

Abstract

Mammalian reproductive tract development is a tightly regulated process that can be disrupted following exposure to drugs, toxicants, endocrine-disrupting chemicals (EDCs), or other compounds via alterations to gene and protein expression or epigenetic regulation. Indeed, the impacts of developmental exposure to certain toxicants may not be fully realized until puberty or adulthood when the reproductive tract becomes sexually mature and altered functionality is manifested. Exposures that occur later in life, once development is complete, can also disrupt the intricate hormonal and paracrine interactions responsible for adult functions, such as spermatogenesis. In this chapter, the biology and toxicology of the male reproductive tract is explored, proceeding through the various life stages including in utero development, puberty, adulthood, and senescence. Special attention is given to the discussion of EDCs, chemical mixtures, low-dose effects, transgenerational effects, and potential exposure-related causes of male reproductive tract cancers.

Figure 1

Endocrine disrupting chemical effects upon the fetal testis. A) Endocrine disrupting chemicals alter both Leydig cell and Sertoli cell function, producing downstream abnormalities. B) As an example, multinucleated germ cells (arrows) are induced in gd18 fetal Fischer rat testis following 2 days of maternal exposure to 250mg/kg/day di-n-butyl phthalate. H&E staining. Bar = 50μm

Figure 2

Cross-section of an adult rat seminiferous tubule demonstrating normal spermatogenesis. The lumen of the seminiferous tubule (*), and interstitial space (+) are identified (bar = 25μm). Along the bottom of the figure, the Individual cell types are labeled and magnified to illustrate their morphology (bar = 3μm). H&E staining.

Figure 3

Chemical structures of model testicular toxicants: A) 2,5-hexanedione, B) 1,2-dibromo-3-chloropropane, C) ethylene-1,2-dimethanesulfonate, and D) carbendazim.