Data from human populations worldwide suggest there has been a substantial decline in male fertility during the past several decades. For example, a comprehensive analysis in the year 2000, of data from >100 studies in Western countries, showed evidence of a decline in human spermatogenesis during the preceding 50 years. Changes in sperm production have coincided with purported increases in the incidence of other reproductive defects –– including hypospadias, cryptorchidism, and testicular germ cell cancers. The combined spectrum of reproductive effects has been termed testicular dysgenesis syndrome (TDS). These observed changes might be associated with the rapid introduction of man-made chemicals in the postwar era, and were originally hypothesized to result from exposure to maternally- or environmentally-derived estrogens.
Subsequent experimental data have provided evidence that male reproductive abnormalities can be induced by developmental exposure to different types of endocrine-disrupting chemicals (EDCs). Given the rapid increase in variety, ubiquity of environmental EDCs, and adverse reproductive effects ascribed to some of these chemicals –– clinical implications might be substantial –– although this is of course dependent on actual doses of EDCs in our environment. The most compelling evidence of a clinical effect of developmental estrogenic exposure on human male reproductive health comes from studies of diethylstilbestrol (DES)-exposed sons. From the 1940s through the 1970s, DES was prescribed to millions of pregnant women to prevent miscarriage. This treatment not only was NOT beneficial, but increased the incidence of a variety of reproductive disorders, including cancers in both male and female offspring, including even the next generation. Although DES daughters have been studied more extensively, in DES sons and in male mice exposed prenatally to DES, the incidence of cryptorchidism, underdeveloped testes, and testicular cancer is increased, and sperm count and quality is decreased.
It should be emphasized, however, that DES given as a drug is many orders of magnitude greater than any clinical exposure to EDCs in the environment. Also, daily treatment with a known dose of drug is very different from sporadic, random exposure to environmental EDCs. Although the lack of information on sources, levels and timing of exposure precludes systematic studies of other developmental estrogenic exposures in humans –– epidemiological studies suggest etiological links between environmental exposures and changes in spermatogenesis and the incidence of testicular germ cell cancers of fetal origin. These multi- and trans-generational effects are assumed to result from epigenetic alterations to the germline, but few studies have directly analyzed germ cells.
Typically, studies of trans-generational effects have involved exposing one generation and monitoring effects in subsequent unexposed generations. This approach, however, has limited human relevance, because both the number and volume of estrogenic contaminants has increased steadily over time, intensifying rather than reducing or eliminating exposure. Using outbred CD-1 mice and a sensitive and quantitative marker of germline development (meiotic recombination), authors tested the effect of successive generations of exposure on the testis. They targeted the germline during a narrow, perinatal window using oral exposure to the synthetic estrogen, ethinyl estradiol. An additional caveat is that ethinyl estradiol is orders of magnitude more potent that many environmental EDCs, e.g. bis-phenol-A (BPA)
A complex 3-generation exposure protocol allowed authors to compare the effects of individual, paternal, and grandpaternal (ancestral) exposure. The data [see attached paper] indicate that multiple generations of exposure not only exacerbate germ cell exposure effects, but also increase the incidence and severity of reproductive tract abnormalities. Taken together, authors conclude that these data suggest that male sensitivity to environmental estrogens is enhanced by successive generations of exposure.
PloS Genet July 2o17; 13: e1006885
Dear Dan, In addition to the issues of this LNT Model, which themselves are far-reaching, this example (along with others) represents a substantial challenge to the claim that “science is ultimately self-correcting”. Very troubling. Thank you for keeping us informed on this very important issue.
PS Further information about the ‘self-correcting’ notion: many papers are more highly cited after they have been retracted: