Environmental anti-androgens and male reproductive health: focus on phthalates and testicular dysgenesis syndrome

Fisher, Jane S.

doi:10.1530/rep.1.00025

Cited by 373 publications

(228 citation statements)

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“…23 It has been hypothesized that endocrine disrupting compounds play a major role in the aetiology of increased incidence of testicular dysgenesis syndrome which gathers decreased quality of semen, cryptorchidism, hypospadias and testicular cancer. 24 Chemicals with hormone-like activity can also disrupt programming of endocrine signalling pathways during development. Indeed, androgen and oestrogen receptors, which play critical but distinct roles in the physiology of sperm cells, are present on male germ cells.…”

Section: Introductionmentioning

confidence: 99%

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Decline of semen quality among 10 932 males consulting for couple infertility over a 20-year period in Marseille, France

Geoffroy-Siraudin¹,

Loundou²,

Romain³

et al. 2012

Asian J Androl

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Semen from 10 932 male partners of infertile couples was analysed and sperm parameter trends were evaluated at the Reproduction Biology Laboratory of the University Hospital of Marseille (France) between 1988 and 2007. After 3-6 days of abstinence, semen samples were collected. Measurements of seminal fluid volume, pH, sperm concentration, total sperm count, motility and detailed morphology of spermatozoa were performed. Sperm parameters were analysed on the entire population and in men with normal total numeration (o40 million per ejaculate). The whole population demonstrated declining trends in sperm concentration (1.5% per year), total sperm count (1.6% per year), total motility (0.4% per year), rapid motility (5.5% per year) and normal morphology (2.2% per year). In the group of selected samples with total normal sperm count, the same trends of sperm quality deterioration with time were observed. Our results clearly indicate that the quality of semen decreased in this population over the study period. Keywords: environment; male infertility; regional differences; semen quality; sperm parameters INTRODUCTION Numerous studies suggest a decline in semen quality in some parts of the world. 1-8 By contrast, other studies have shown no evidence of deteriorating semen quality. 9-16 Some studies concern infertile couples, while others analyse normal sperm parameters. Thus, a worldwide decreasing trend in semen parameter values can be neither confirmed nor rejected. 17 It was recently reported that fecundity is affected by this decrease. 18,19 It was speculated that decreasing sperm parameters are in response to adverse environmental factors. Nevertheless, the observed discrepancies between studies suggest regional differences in semen quality. [20][21][22] Variations in environmental factors, industrial pollution and/or lifestyle could explain these discrepancies. A large number of environmental factors can pollute air, drinking water and food. This can directly alter the male gonad by blood-testis barrier disruption and cellular toxicity, or disrupt androgen biosynthesis and action. Among these environmental factors, oestrogenic or anti-androgenic endocrine disrupting compounds inhibit critical cellular process controlling steroidogenesis in Leydig cells and androgen binding to the androgen receptor. 23 It has been hypothesized that endocrine disrupting compounds play a major role in the aetiology of increased incidence of testicular dysgenesis syndrome which gathers decreased quality of semen, cryptorchidism, hypospadias and testicular cancer. 24 Chemicals with hormone-like activity can also

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Decline of semen quality among 10 932 males consulting for couple infertility over a 20-year period in Marseille, France

Geoffroy-Siraudin¹,

Loundou²,

Romain³

et al. 2012

Asian J Androl

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“…Vinclozolin is a fungicide used in agricultural fruit crops, such as grapes for the wine industry (Kelce et al 1994, Fisher 2004. Vinclozolin is an anti-androgenic compound that is metabolized into further anti-androgenic compounds (Kelce et al 1994).…”

Section: Introductionmentioning

confidence: 99%

Transgenerational epigenetic effects of the endocrine disruptor vinclozolin on pregnancies and female adult onset disease

Nilsson¹,

Anway²,

Stanfield³

et al. 2008

Reproduction

167

106

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Endocrine disruptor exposure during gonadal sex determination was previously found to induce male rat adult onset transgenerational disease (F1-F4 generation), and this was associated with an alteration in the epigenetic (i.e., DNA methylation) programming of the male germ line. The current study was designed to characterize the transgenerational disease phenotypes of the female adult offspring. Pregnant rats (F0 generation) were treated transiently with vinclozolin (i.e., fungicide with anti-androgenic activity) on embryonic (E) days E8-E14 of gestation. F1 control and vinclozolin generation offspring from different litters were mated to produce F2 offspring, and similarly F2 generation animals produced F3 generation offspring. Observations demonstrated that 9 out of 105 pregnant rats (8.6%) from the vinclozolin F1-F3 generations exhibited uterine hemorrhage and/or anemia late in pregnancy. None (0 out of 82) of the control F1-F3 generation females had similar pregnancy problems. Complete blood cell counts and serum chemistry profiles demonstrated that selected vinclozolin generation animals, but not controls, exhibited marked regenerative anemia in late pregnancy. Examination of kidney histology revealed moderate or severe glomerular abnormalities in 67% of the vinclozolin F2 and F3 generation adult females compared with 18% of the controls. Adult female vinclozolin generation animals also developed various types of tumors in 6.5% of the animals (11 out of 170), while 2% of control-line animals (3 out of 151) developed mammary tumors. Observations demonstrate that vinclozolin exposure during gonadal sex determination promotes a transgenerational increase in pregnancy abnormalities and female adult onset disease states.

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“…It has been reported that the fetal hormonal disruption induced either by chemical anti-androgens such as flutamide or by different environmental anti-androgen compounds (e.g., vinclozolin, phthalates) gives rise to a wide range of reproductive system abnormalities such as hypospadias, undescended testes, developmental testicular alterations (Fisher 2004, Crews & McLachlan 2006, Gray et al 2006, Newbold et al 2006, and particularly to a long-term apoptosis of germ cells in the adult testis (Omezzine et al 2003, Bozec et al 2004, Uzumcu et al 2004 transmitted by male through at least four generations (Anway et al 2005). These observations support the concept of a fetal and transgenerational programming of adult testicular germ cell apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Alterations of Sertoli cell activity in the long-term testicular germ cell death process induced by fetal androgen disruption

Benbrahim‐Tallaa¹,

Siddeek²,

Bözec³

et al. 2007

Journal of Endocrinology

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Fetal androgen disruption, induced by the administration of anti-androgen flutamide (0 . 4, 2, and 10 mg/kg day) causes a long-term apoptosis in testicular germ cells in adult male rat offspring. One of the questions raised by this observation is the role of the Sertoli cells in the adult germ cell apoptotic process. It is shown here that Sertoli cells originating from 15-day-old rats treated in utero with the anti-androgen (10 mg/kg d) did no longer protect adult germ cells against apoptosis. Indeed, untreated spermatocytes or spermatids exhibited increased (P!0 . 0001) active caspase-3 levels when co-cultured with Sertoli cells isolated from rat testes exposed in utero to the anti-androgen. This alteration of Sertoli cell functions was not due to modifications in the androgen signal in the adult (90-day-old) animals, since plasma testosterone and estradiol, androgen receptor expression, and androgentargeted cell number (e.g., Sertoli cells in the seminiferous tubules) were not affected by the fetal androgen disruption. In contrast, this inability of Sertoli cells to protect germ cells against apoptosis could be accounted for by the potential failure of Sertoli cell functions. Indeed, adult testes exposed in utero to anti-androgens displayed decreased levels of several genes mainly expressed in adult Sertoli cells (anti-Mullerian hormone receptor type II (AMHR2), Cox-1, cyclin D2, cathepsin L, and GSTa). In conclusion, fetal androgen disruption may induce alterations of Sertoli cell activity probably related to Sertoli cell maturation, which potentially leads to increased adult germ cell apoptosis.

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Environmental anti-androgens and male reproductive health: focus on phthalates and testicular dysgenesis syndrome

Cited by 373 publications

References 66 publications

Decline of semen quality among 10 932 males consulting for couple infertility over a 20-year period in Marseille, France

Decline of semen quality among 10 932 males consulting for couple infertility over a 20-year period in Marseille, France

Transgenerational epigenetic effects of the endocrine disruptor vinclozolin on pregnancies and female adult onset disease

Alterations of Sertoli cell activity in the long-term testicular germ cell death process induced by fetal androgen disruption

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