Fetal sexuality

Can we expect environmental endocrine disruptors to affect the sexual development of the human fetus In my opinion, the answer is an absolute yes, if only because we know that endocrine disruptors act like foreign hormones and thereby disrupt natural hormone physiology. Hormones are critical in fetal sexual and brain development. Exposure of the fetus to hormones can produce profound changes in development. In the case of androgenic hormones, for example, exposure diverts a genetic female to take on the phenotypic appearance of a male, and these hormones change the areas of the brain that ordinarily differ between the sexes (sexually dimorphic areas). 

Still other constructs have been mired in biological ignorance. Consider, for example, fetal sexual development and certain attitudes about it. The ancient Greeks believed that the sex of the fetus is determined by the heat of the male partner during copulation—the more heated the passion, the greater the probability of a male fetus. Aristotle advised men to copulate in the summer if they wanted male heirs. The idea became... 

Gestation is the period during which each individual s sexuality is first expressed and shaped. But impact on the organization of fetal sexuality seems to be most effective during certain sensitive gestational periods, windows of vulnerability. The exact periods for human behavioral effects of sex hormones remain unknown. The period 8—24 weeks of gestation may be most critical because that s when testosterone secretion surges in male fetuses, but there may be multiple sensitive... 

Testosterone, the principal male sex steroid hormone, is synthesized in five steps from cholesterol, as shown below. In the last step, five isozymes catalyze the 17/3-hydroxysteroid dehydrogenase reactions that interconvert 4-androstenedione and testosterone. Defects in the synthesis or action of testosterone can impair the development of the male phenotype during embryogenesis and cause the disorders of human sexuality termed male pseudohermaphroditism. Specifically, mutations in isozyme 3 of the 17/3-hydroxysteroid dehydrogenase in the fetal testis impair the for-... 

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... 

Pesticides accumulate in fetal cells and reproductive organs in mammals, birds, and fish due to biochemical processes. This is noted especially often for OCPs, which were observed in large amounts (up to 6.8 mg/kg) in, for example, the sexual organs of hares, rabbits, pheasants, green-winged teals, and in white-eyed and red-headed ducks. They were found in animal embryos, as well as in black thrush eggs and in pheasant embryos and amniotic fluid (up to 73.0 mg/kg) [3]. 

The plasticizer diethylhexyl phthalate induces malformations by decreasing fetal testosterone synthesis during sexual differentiation in the male rat. Toxicol Sci 58 339-349... 

Male patients must always use a latex condom during sexual contact with women of childbearingpotential even if a successful vasectomy has been performed. Thalidomide is present in the semen of patients taking the drug. Report suspected fetal exposure to thalidomide to FDA (1-800-FDA-1088). 

Fig. 1. Diagram of the major reproductive life cycle phases, commencing with sexual maturation and moving through fertilization, fetal development, parturition and postnatal development and ending with a sexually mature individual capable of starting the cycle over again.

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... 

Much has been said about the positive effects of vitamin E (a-tocopherol) on sexual performance and ability in humans. Unfortunately, there is little scientific rationale to substantiate such claims. The primary reasons for attributing a positive role in sexual performance to vitamin E come from experiments on vitamin E deficiency in laboratory animals. In such experiments the principal manifestation of this deficiency is infertility, although the reasons for this condition differ in males and females. In female rats there is no loss in ability to produce apparently healthy ova, nor is there any defect in the placenta or uterus. However, fetal death occurs shortly after the first week of embryonic life, and fetuses are reabsorbed. This situation can be prevented if vitamin E is administered any time up to day 5 or 6 of embryonic life. In the male rat the earliest observable effect of vitamin E deficiency is immobility of spermatozoa, with subsequent degeneration of the germinal epithelium. Secondary sex organs are not altered and sexual vigor is not diminished, but vigor may decrease if the deficiency continues. 

Parks, L.G., J.S. Ostby, C.R. Lambright, B.D. Abbott, G.R. Klinefelter, N.J. Barlow, and L.E. Gray Jr. 2000. The plasticizer DEHP induces malformations by decreasing fetal testosterone syntheseis during sexual differentiation in the male rat. Toxicol. Sci. 58(2) ... 

M (decreased fetal testosterone Parks et al. 2000 synthesis during male sexual differentiation)... 

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