Male reproductive system fetal development

RE Peterson University of Wisconsin-Madison, Madison, Wl Determine the mechanisms by which 2,3,7,8-TCDD adversely affects the male reproductive system of rats exposed in adulthood or during fetal and neonatal development ... 

The male reproductive system is at risk during fetal development in utero, postnatally during puberty, and during the male reproductive lifetime with... 

Some phthalates, such as DEHP, are endocrine dismptors that affect the developing male reproductive system by interrupting the production of fetal testosterone and the protein involved in testicular descent, insuUn-Uke 3 (insl3), while other phthalates, such as DEP, are not endocrine dismptors. 

In some animals, consumption of a phytoestrogen-rich diet can cause temporary infertility and reproductive system disorders (Irvine, 1999). In humans, lower testosterone levels and a decline in human semen quality over the past century have been luiked to increased exposure to environmental endocrine disrupters (EDCs) (Sharpe and Skakkebaek, 1993). Furthermore, cases of sexual impotence have been reported in males exposed to synthetic estrogens in the pharmaceutical industry (Mattison et al., 1990). If this might be the case, the fetal-prepubertal period and Sertoli cell development would be of critical importance (Sharpe and Skakkebaek, 1993). However, an adverse effect of phytoestrogens on male fertility has yet to be proven. Recent work (Mitchell et al., 2001) addressing this point led to the conclusion that up to 40 mg/day of isoflavones over a two-month period had no effects on gonadotrophin and... 

Reproductive toxicity to 2,3,7,8-TCDD has been demonstrated in animals. "" The effects include pre- and postimplantation losses in females, morphologic and functional changes in male and female reproductive organs, and hormonal imbalance in both sexes. A number of developmental effects have been observed in animals acutely exposed to 2,3,7,8-TCDD by the oral route. Effects observed in offspring of animals include cleft palate, kidney anomalies, immune system damage (thymic atrophy and immunosuppression), impaired development of the reproductive system, decreased growth, and fetal/newborn mortality. 

Two important aspects of early development of the reproductive tract are that the fetal gonad is structurally indifferent in male and female embyros and that the fetal reproductive system can therefore develop as male or female. Thus, the first major step in development of the reproductive system is establishing gonadal sex. Sex of the embryo depends on whether the spermatozoon carries an X or Y chromosome, and sexual differentiation of the indifferent structures in the gonad is necessary to form the male or female reproductive tract. The SRY gene on the Y chromosome is needed for testicular... 

The animal database provides strong evidence that developmental toxicity is a sensitive end point following 2,3,7,8-TCDD exposure. Structural malformations, functional alterations (including impaired development of reproductive system), decreased growth, and fetal/newbom mortality have been observed in several animal species. Limited human data on the developmental toxicity of CDDs is available. Most of these studies examined the occurrence of birth defects in children of males exposed to 2,3,7,8-TCDD. Deficiencies in the human data preclude drawing firm conclusion on the potential of 2,3,7,8-TCDD to induce developmental effects in humans. However, the animal data suggest that 2,3,7,8-TCDD is a likely human developmental toxicant. 

Sexual differentiation of the central nervous system also occurs during fetal development, and it is equally fundamental to reproductive function during adulthood. Adult males exhibit a relatively continuous pattern of gonadotropin secretion from the hypothalamic-pituitary axis and are therefore fertile throughout their reproductive lifetime. In contrast, adult females exhibit a cyclical pattern of gonadotropin secretion and are fertile only during the transient period that follows ovulation during each reproductive cycle. This fundamental difference is due to irreversible... 

EPA s review of recent epidemiologic studies of enviroiunental lead e q)0-sure and reproductive function concludes that there is strong evidence that increasing lead exposure is associated with reduced male fecundity or fertility, decreases in sperm count, and reduced sperm velocity and motility. EPA s draft report further concludes that deleterious associations with sperm count and quality are observed in occupationally exposed men who have mean BLLs as low as 20-45 pg/dL. EPA concluded that there was some association between maternal lead exposure and low birth weight toxicologic studies in animals have shown that lead exposme during early fetal development can result in abnormal retinal development and alterations in the developing hematopoietic and hepatic systems. 

Developmentally, the reproductive system of vertebrates has two outcomes, male or female. While it is convenient to envision these two outcomes as dichotomous, the reality is not so simple. As discussed above, genetic males do not always develop into morphological ones, not even in mammals. Changes in the chemical environment in which fetal or larval animals develop are important, as they can disrupt the endogenous endocrine signals, causing alterations in reproductive development. Furthermore, the plasticity... 

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