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Animal Reproduction Science 60–61 2000 121–130 www.elsevier.comrlocateranireprosci
Deteriorating trends in male reproduction: idiopathic or environmental?
D.N. Rao Veeramachaneni
Animal Reproduction and Biotechnology Laboratory, Department of Physiology, College of Veterinary Medicine and Biomedical Sciences, Colorado State UniÕersity, Fort Collins, CO 80523-1683, USA
Abstract
Recent reports portend deterioration in male reproductive health in several human populations. Similar trends might exist in domestic animals, but data are not available because of the inherent
nature of animal husbandry practices — culling of the reproductively inefficient food- and fiber-producing animals at an early age. Although the causes for this deterioration are unknown, a
variety of endocrine-mimicking environmental pollutants have been implicated. Data for relevant laboratory animal models exposed to several classes of suspect chemicals indicate that a variety of
chemicals ubiquitously present in the environment can disrupt normal reproductive phenomena in the male at exposure rates encountered in nature. Data are presented for occurrence of cryp-
torchidism, carcinoma in situ of the testis, acrosomal malformations, and impaired sexual function
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following in utero andror postnatal exposures to pesticides e.g., DDT and vinclozolin , high- Ž
. volume industrial chemicals e.g., alkylphenols and phthalates , and commonly occurring organic
Ž and inorganic chemical contaminants in drinking water
e.g., chemical mixtures and water .
disinfection byproducts . These observations are discussed in the context of similar, so-called idiopathic conditions encountered in stallions. q 2000 Elsevier Science B.V. All rights reserved.
Keywords: Testicular carcinoma in situ; Intratubular germ cell neoplasia; Acrosomal dysgenesis; Sexual dysfunction; Chemical contaminants; Environmental pollutants
1. Introduction
Ž Recent studies of human populations in several countries Carlsen et al., 1992, Auger
. et al., 1995 showed that the incidence of abnormalities of male genitalia is on the rise
Correspondence author. Tel.: q1-970-491-1769r1770; fax: q1-970-491-3557. Ž
. E-mail address: raocvmbs.colostate.edu D.N. Rao Veeramachaneni .
0378-4320r00r - see front matterq 2000 Elsevier Science B.V. All rights reserved. Ž
. PII: S 0 3 7 8 - 4 3 2 0 0 0 0 0 1 1 3 - 5
and that the quality of semen has declined over the past 50 years. Although other reports Ž
. Fisch et al., 1996; Paulsen et al., 1996 revealed no downward trend in semen quality,
the subjects involved in these studies represented a limited geographic area. Another meta-analysis of data involving bulls, boars, and rams also did not find any decline in
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sperm counts over the last 60 years Setchell, 1997 . Whether test populations of these farm animal species already had been selected for their reproductive efficiency, or if
there was any decline in the quality of sperm is not known. Although data for many animal species might be compiled, this would likely have limited value because of
non-standard conditions of evaluation, particularly collection of semen in a manner precluding estimation of daily sperm production.
The incidence of testicular cancer, the most frequent malignancy in young men, also has increased three- to four-fold during the past 50 years in several human populations,
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particularly in the Western world Adami et al., 1994; Bosl and Motzer, 1997 .
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Likewise, epidemiologic data Laumann et al., 1999 , together with increased demand for clinical services to correct erectile dysfunction, indicate that sexual dysfunction in
human populations is more prevalent than previously thought. Similar trends might also exist in domestic animals, but data are not available largely because of the inherent
nature of animal husbandry practices — culling of the reproductively inefficient food- and fiber-producing animals at an early age. The implications of these data for human
populations have caused great concern. The relatively short time period during which these changes have occurred in human populations has been inferred as evidence that the
cause is environmental rather than genetic.
Many chemicals in the environment, including some pharmaceutical compounds, are capable of mimicking the inherent actions of reproductive hormones and, hence, have
the ability to disrupt the neuroendocrine system or function of the gonads directly. Estrogens or estrogen-like chemicals have been implicated as the causative agents for
cryptorchidism, testicular cancer, or other testicular abnormalities and declining sperm
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counts Sharpe and Skakkebaek, 1993; Toppari et al., 1996 . There is convincing evidence that a variety of compounds with endocrine-mimicking characteristics —
pesticides, alkylphenols, phthalates, disinfection byproducts of water purification, com- mon chemical contaminants, phytoestrogens and estrogenic mycotoxins — are found in
Ž packaged foods, drinking water, lakes, and oceans Colborn et al., 1993; Jobling et al.,
. 1995 . Surprisingly, in spite of an ominous potential for catastrophic health hazards,
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there is little information on long-term consequences in adult life of exposure to endocrine-disrupting chemicals in utero or during infancy. In most cases of reproductive
dysfunction, because the cause and effect are separated by a long interval, it is impossible to ascribe a current clinical condition to an etiologic agent or event that
impacted many years earlier and thus the existing condition commonly would be labeled as idiopathic.
Our laboratory is studying whether some common perturbations of the male reproduc- tive system or sperm are truly idiopathic or sequelae to developmental exposure to
common environmental pollutants. Some of these experimental paradigms in laboratory animals vis-a-vis clinical cases of stallions manifesting perturbed reproductive phenom-
`
ena — occurrence of testicular carcinoma in situ, unique defects in morphogenesis of sperm such as acrosomal dysgenesis, and sexual dysfunction — are discussed herein.
2. Carcinoma in situ of the testis
