Testicular Tumors in Mice

Susceptibility of Seven Inbred Strains and the F1 Hybrids to Estrogen-Induced Testicular Tumors and Occurrence of Spontaneous Testicular Tumors in Strain BALB/c Mice, 1960

Abstract

Strain BALB/c mice are susceptible to the development of estrogen-induced interstitial-cell testicular tumors.

Mice of this strain and 6 other inbred strains were tested for susceptibility to these tumors by subcutaneous implantation of pellets containing 20 percent diethylstilbestrol in cholesterol.

Strain BALB/c mice (incidence = 80%) were far more susceptible than the most susceptible (strain DBA/2 = 12%) of the other strains.

F1 hybrids derived by mating BALB/c females to males of the 6 other strains were tested for susceptibility by the same procedure.

Those procured from strain DBA/2 (incidence = 67%) or strain Y (incidence = 65%) were the most susceptible and those from strain I (incidence = 3%) or strain RIII (incidence = 0%) were the most resistant. The incidence of gross spontaneous testicular tumors in 154 BALB/c mice was 0 percent. Three mice had microscopic lesions of the testes. In a testis of one, connective-tissue elements predominated. Testes of the other 2 mice contained small areas of interstitial-cell hyperplasia.

References

  • Susceptibility of Seven Inbred Strains and the F1 Hybrids to Estrogen-Induced Testicular Tumors and Occurrence of Spontaneous Testicular Tumors in Strain BALB/c Mice, JNCI: Journal of the National Cancer Institute, Volume 25, Issue 5, Pages 1069–1081, doi.org/10.1093/jnci/25.5.1069, November 1960.
  • Featured image credit immuno-oncologynews.
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Testicular Dysgenesis Syndrome (TDS)

An increasingly common developmental disorder with environmental aspects, 2001

Abstracts

Numerous reports have recently focused on various aspects of adverse trends in male reproductive health, such as the rising incidence of testicular cancer; low and probably declining semen quality; high and possibly increasing frequencies of undescended testis and hypospadias; and an apparently growing demand for assisted reproduction.

Due to specialization in medicine and different ages at presentation of symptoms, reproductive problems used to be analysed separately by various professional groups, e.g. paediatric endocrinologists, urologists, andrologists and oncologists.

This article summarizes existing evidence supporting a new concept that poor semen quality, testis cancer, undescended testis and hypospadias are symptoms of one underlying entity, the testicular dysgenesis syndrome (TDS), which may be increasingly common due to adverse environmental influences.

Experimental and epidemiological studies suggest that TDS is a result of disruption of embryonal programming and gonadal development during fetal life. Therefore, we recommend that future epidemiological studies on trends in male reproductive health should not focus on one symptom only, but be more comprehensive and take all aspects of TDS into account. Otherwise, important biological information may be lost.

Evidence from animal studies and wildlife

There is a wealth of data showing that male animals exposed in utero or perinatally to exogenous oestrogens (diethylstilbo-estrol, ethinyl oestradiol, bisphenol A) and anti-androgens [flutamide, vinclozolin, 1,1-dichloro-2, 2-bis(p-chlorophenyl)ethylene (DDE), 1,1,1-trichloro-2, 2-bis(4-chlorophenyl)ethane(DDT)] develop hypospadias, undescended testis, low sperm counts or, in the worst case, intersex conditions, teratomas and Leydig cell tumours. A recent report provided experimental evidence that ubiquitous phthalates, can also hamper testicular descent in rats when administered prenatally.

References

  • Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects, Endocrinology, Human reproduction (Oxford, England), NCBI PubMed, PMID: 11331648, 2001 May.
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Pathways of endocrine disruption during male sexual differentiation and masculinization

Best practice & research, Clinical endocrinology & metabolism, 2006

Abstracts

After testis formation, further development of a male phenotype (masculinization) is driven by three hormones from the foetal testis: anti-Müllerian hormone, insulin-like factor, and testosterone. These hormones divert the development of reproductive and other organs from female to male and also play a role in testis development. The hormone dependence of masculinization renders this process inherently susceptible to disruption by factors that interfere with hormone production, bioavailability, metabolism, or action. This susceptibility is illustrated by the high prevalence of congenital masculinization disorders (cryptorchidism, hypospadias) and disorders in young adult men (low sperm counts, testis cancer), which may also stem from maldevelopment (dysgenesis) of the foetal testis. Testicular dysgenesis occurring in humans, or which is induced in animal models by foetal exposure to certain phthalates, is associated with impaired hormone production by the foetal testis. There is currently no definitive evidence that exposure of humans to environmental chemicals can induce testicular dysgenesis and/or impair masculinization, though pathways via which this could potentially occur are established.

Concern about endocrine disruption of masculinisation has been fuelled by two pieces of information. The first is the evidence that mild disorders of the masculinisation process in humans are common and may be increasing in prevalence. Chief amongst these are the occurrence of cryptorchidism (testicular maldescent) and hypospadias (an abnormality in position of the urethral opening on the penis). However, it has also become increasingly apparent that male reproductive disorders which manifest in young adulthood (low sperm counts, testicular germ cell cancer) may also originate from disruption of the same early processes. The second factor driving concern about endocrine disruption of masculinisation is that this process, via which the basic female ‘set-up’ programme is rewritten to deliver a phenotypic male, is absolutely hormone-dependent , and is thus inherently susceptible to disruption by factors that can alter production or action of these hormones.

It is also not difficult to imagine that the different steps that comprise early testis development could go awry to a greater or lesser extent; the result of this would be termed dysgenesis. At its worst, widespread failure of normal seminiferous cord formation could occur, which would be bound to result in consequent failure of spermatogenesis, and therefore of fertility, in adulthood. This can occur in some patients due to certain chromosomal disorders (e.g. XY) in which a Y chromosome is present; such patients are frequently under-masculinised with ambiguous genitalia and are at high risk of developing testicular germ cell cancer.

It is becoming increasingly apparent that expression of AR, and probably of steroid receptors in general, is regulated primarily via alteration of the rates of receptor degradation rather than from altering the rate of receptor gene transcription and mRNA translation. This has been most clearly demonstrated for the AR, in which altered proteosomal degradation has been shown to occur in response to abnormally high exposure to potent oestrogens. This ability of over-exposure to oestrogens to dramatically reduce AR expression in reproductive target tissues in the male rat has been well described, and raises the possibility that environmental oestrogenic chemicals could induce similar effects and thus interfere with masculinisation. However, though there are isolated examples where such effects have been claimed, it appears that where the action of a potent (e.g. diethylstilboestrol) and a weak environmental oestrogen (e.g. bisphenol A) are compared directly, only the potent oestrogen is able to induce such an effect, and even then only at very high doses. Nevertheless, as this effect of oestrogen action is still poorly understood, it remains possible that some environmental chemicals might be able to target this particular pathway and thus interfere with androgen action during masculinisation.

References

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Chemical Treatment for Sex Offenders

Castration of Sex Offenders: Prisoners’ Rights Versus Public Safety, 2003

Abstract

Sexual victimization of children and adults is a significant treatment and public policy problem in the United States. To address increasing concerns regarding sex offender recidivism, nine states have passed legislation since 1996 authorizing the use of either chemical or physical castration. In most statutes, a repeat offender’s eligibility for probation or parole is linked to acceptance of mandated hormonal therapy. Future legal challenges to this wave of legislation will probably include arguments that such laws violate constitutional rights guaranteed to the offender by the First, Eighth, and Fourteenth Amendments. When the promise of freedom is predicated on mandated treatment, the clinician must carefully assess the validity of informed consent.

The first reported use of hormonally based medications to reduce pathological sexual behavior in men occurred in 1944 when the progesteronal hormonal compound diethylstilbestrol (previously used as female contraceptives) was prescribed to lower male testosterone.

Alan Turing was famously subjected to chemical castration to ‘cure’ his homosexuality in 1952, and committed suicide two years later.

In 1959, a report discussed the clinical use of DES (Stilboestrol) for suppression of sexual behaviour of chronically ill male psychiatric patients.

Diethylstilbestrol was just the first of many such drugs, as by the 1960s, others, notably including medroxyprogesterone acetate (MPA), were being used to treat sex offenders and others displaying sexually-deviant behavior, like exhibitionists. MPA remained one of the major drugs in chemical castration, joined by others in later years as the science progressed.

2019, Alabama : A new bill, passed by the state legislature, awaiting the governor’s signature – see the proposed law – says a judge must order anyone convicted of a sex offense involving a child under the age of 13 to start receiving testosterone-inhibiting medication a month before their release from prison.

References

Testis abnormalities in neonatally DES-exposed rats

Induction of reproductive tract developmental abnormalities in the male rat by lowering androgen production or action in combination with a low dose of diethylstilbestrol: evidence for importance of the androgen-estrogen balance

2002 Study Abstract

This study tested the hypothesis that testis/reproductive tract abnormalities induced in the rat by neonatal treatment with diethylstilbestrol (DES) result from disturbance of the androgen-estrogen balance. Male rats were treated neonatally with a dose of DES (0.1 micro g) that induced either no or small effects on its own or with a dose (10 micro g) that induced major reproductive tract abnormalities.

To allow quantification, the abnormalities chosen for study were distension of the rete testis and efferent ducts and reduction in epithelial cell height in the efferent ducts and vas deferens.

To alter the androgen-estrogen balance, other rats were treated with DES (0.1 micro g) in combination with a treatment to suppress either androgen production [GnRH antagonist (GnRHa)] or androgen action (flutamide); other rats were treated with GnRHa or flutamide alone. Testosterone levels were measured to verify the effects of treatment.

Combined administration of DES (0.1 micro g) plus GnRHa or flutamide induced significantly greater distension/overgrowth of the rete testis and efferent ducts (ED) and a reduction in epithelial cell height of the ED than did DES (0.1 micro g) administered alone. Neither GnRHa nor flutamide affected rete or ED distension when administered alone, but both significantly reduced ED epithelial cell height. Neonatal treatment with bisphenol-A (100 micro g) with or without GnRHa had no significant effect on any of these parameters. In contrast to the ED, a reduction in cell height of the vas deferens was induced to an equal extent by DES (10 micro g), DES (0.1 micro g) with GnRHa, and GnRHa alone, suggesting greater sensitivity of this tissue to both androgen and estrogen action. The induction of major abnormalities in rats treated with DES (10 micro g) was coincident with loss of androgen receptor immunoexpression in affected tissues. Reduced androgen receptor immunoexpression was also induced by combined treatment with DES (0.1 micro g) plus GnRHa or flutamide, whereas treatment with any of these compounds alone had no or only minor effects.

These findings suggest that reduced androgen action sensitizes the reproductive tract to estrogens, demonstrating that the balance in action between androgens and estrogens, rather than their absolute levels, may be of fundamental importance in determining normal or abnormal development of some regions of the male reproductive tract.

Discussion

The primary aim of the present studies was to test the hypothesis that testis/reproductive tract abnormalities, which are induced in the neonatal rat by treatment with relatively high doses (10 μg) of DES, result from disturbance of the androgen-estrogen balance rather than from the estrogenic effect of DES alone (23, 24). This was tested by treating male rats neonatally with a dose of DES (0.1 μg) that induced either no or small effects on its own and combining this with a treatment that suppressed either androgen production (GnRHa) or androgen action (the androgen receptor antagonist flutamide). The results show unequivocally that either of these combined treatments was able to significantly induce greater abnormalities of the rete testis and efferent ducts than did 0.1 μg DES administered alone. Neither GnRHa nor flutamide induced any of the abnormalities when administered alone, whereas treatment with a high dose of DES (10 μg) induced major abnormalities coincident with loss of immunoexpression of the AR in affected tissues. Reduced immunoexpression of AR was also induced by combined treatment with 0.1 μg DES and GnRHa or flutamide, whereas treatment with any of the compounds alone had no or only minor effects on AR immunoexpression. These results together with our previous demonstration that induction of reproductive abnormalities by neonatal treatment with 10 μg DES can be blocked by cotreatment with testosterone (24) provide support for the suggestion that these abnormalities result from a disturbance of the normal androgen-estrogen balance rather than from a lowering of androgen action or an elevation of estrogen action per se. A slightly alternative view is that the level of androgen exposure determines the sensitivity of the developing male reproductive tract to estrogens, such that low androgen levels increase sensitivity to estrogens and vice versa. Either interpretation implies that normal or abnormal development of the male reproductive system may be governed by the relative levels (balance) of androgens and estrogens rather than by the absolute level of either hormone. This has several implications, as discussed below.

The finding of key importance from the present study is the demonstration that combined treatment with a relatively low dose (0.1 μg) of DES plus treatments to either lower androgen production (GnRHa) or block androgen action (flutamide) was able to induce significantly greater distension of the rete testis or efferent ducts, as measured by lumenal area, than any of the treatments administered alone; of the latter, only 0.1 μg DES had any (minor) effect on its own. Although these contrasting effects were clear-cut, the use of another end point, epithelial cell height in the efferent ducts or proximal vas deferens, resulted in a more complex picture, as all single treatments other than bisphenol-A exerted significant adverse effects. In the efferent ducts it was still clear that combined treatment with 0.1 μg DES plus either GnRHa or flutamide was able to reduce epithelial cell height to a significantly greater extent than any of these treatments individually; indeed, the combined treatments caused an effect of similar magnitude to that induced by treatment with 10 μg DES alone. In contrast, several of the individual treatments (10 or 0.1 μg DES plus GnRHa) induced very similar effects on epithelial cell height in the proximal vas deferens, and combined treatment with 0.1 μg DES and either GnRHa or flutamide was unable to exacerbate this effect compared with administration of 0.1 μg DES or GnRHa alone. This suggests that more posterior parts of the reproductive tract, such as the vas deferens, may be more sensitive to androgens and estrogens than the more anterior parts (rete and efferent ducts) such that all single treatments, other than flutamide and bisphenol-A, induced maximal effects. This makes it fundamentally difficult to test whether the androgen-estrogen balance is as important in the vas as it appears to be in the more anterior regions of the tract.

Although the different responses of epithelial cells from the efferent ducts and vas deferens to altered androgens and estrogens remain to be explained, the fact that normal development of the rete and efferent ducts appear particularly dependent on a normal androgen-estrogen balance may have relevance to findings in ERα knockout (ERKO) mice. The latter exhibit distension of both the rete and efferent ducts in the face of supranormal testosterone levels and the absence of normal expression of ERα in the epithelium of both the rete and efferent ducts. This raises the possibility that the abnormalities reported in ERKO males do not result only from the loss of ERα-mediated estrogen action, but might also be affected by disturbance of the androgen-estrogen balance, although in the opposite direction (supranormal androgen plus subnormal estrogen action) to that induced in the present studies. However, this would fail to explain why aromatase knockout mice, which also have elevated testosterone levels, do not show the same structural abnormalities as ERKO mice. Nevertheless, the present findings caution that whenever androgen and/or estrogen levels are altered substantially from normal in the developing male, changes resulting from disruption of the androgen-estrogen balance should be kept in mind.

There are examples in the literature indicating a role for the androgen-estrogen balance. For example, gynecomastia in men can be induced either by raising estrogen levels or by lowering androgen levels, such that in either situation the androgen-estrogen balance is altered in favor of estrogens. Another example is clover disease, in which castrated rams that fed on Mediterranean clover containing weakly estrogenic phytoestrogens died from urinary retention due to overgrowth of the bulbo-urethral glands, which are both an estrogen and an androgen target. Intact rams or castrated rams treated with androgens and fed on the same clover showed no overgrowth or ill effects. Thus, in castrated rams with low androgen levels, phtyoestrogens induced a catastrophic effect, whereas in intact rams with high androgen levels or in castrated rams supplemented with androgens, no effect occurred despite exposure to the same “estrogen” level. In many respects this example arises from a situation in which hormonal status would be comparable to that induced in the present studies by combined treatment with 0.1 μg DES plus GnRHa. There may be other examples in which a role for altered androgen-estrogen balance could be important. For example, abnormal prostatic structure and growth induced by neonatal estrogen treatment are known to involve both altered androgen and estrogen action, and this may apply also to reproductive tissues in the female.

If the relative, rather than absolute, levels of androgens and estrogens are important for normal development and/or function of the testis and reproductive tract, as our findings suggest, how would this work at the cellular level, given that the present understanding is that androgens and estrogens act via separate, if related, signaling systems? There are various possibilities based on published data, although none has been shown to operate physiologically. For example, estrogens can trans-activate the AR/ARA70 complex at high concentrations and thus activate the transcription of androgen-dependent genes, although DES could not exert this effect. Interaction between the C-terminal domain of ERα and the AR has been demonstrated using two-hybrid systems, and cotransfection of the two receptors into CV-1 cells has demonstrated a mutual ability of each receptor to antagonize trans-activation mediated by ligand binding to the other receptor. An alternative explanation might be activation of the Src-Raf1/Shc-Erk2 pathway, in which androgens and estrogens may induce assembly of a novel ternary complex comprising the AR, ER (either ERα or ERβ), and Src. This complex triggers activation of the protein kinase domain of Src and downstream effects, such as cell proliferation or inhibition of apoptosis. The androgen-AR and estrogen-ER complexes bind to separate domains on the Src protein, and antagonists of either the AR or ER can block activation of this pathway by either androgens or estrogens. Our recent findings that expression of classical androgen-regulated genes in the prostate can also be regulated by estrogens and that antiestrogens can block androgen activation of these genes in vivo are consistent with the activation of such a pathway.

Regardless of the pathway involved, the present findings have implications for issues such as endocrine disruptors, in which considerations of risk are focused largely on the absolute dose/level of exposure as opposed to the relative levels of androgen and estrogens. The present study has shown that combined treatment with a weak environmental estrogen, bisphenol-A, plus a GnRHa was unable to induce any of the abnormalities induced by 0.1 μg DES plus GnRHa, suggesting that in this situation the estrogenicity of the bisphenol-A, when injected in moderately high amounts (100 μg/injection), was still insufficient to perturb the androgen-estrogen balance. Whether this balance can be disturbed by higher doses of this or other environmental estrogens or in combination with environmental antiandrogens are obvious questions that need to be addressed.

In summary, the present findings add to the growing evidence of a close interrelationship between the actions of androgens and estrogens in regulating normal and abnormal development of the male reproductive system. Our findings suggest that the balance in action between androgens and estrogens, rather than the absolute levels of either hormone, may be of fundamental importance at least for some regions of the reproductive tract. From a physiological perspective, local regulation of relative levels of androgens and estrogens, for example by differential expression of aromatase or 5α-reductase, may be critical factors that ensure an appropriate steroid milieu for specific regions of the reproductive system

References

  • Full study (free access) : Induction of reproductive tract developmental abnormalities in the male rat by lowering androgen production or action in combination with a low dose of diethylstilbestrol: evidence for importance of the androgen-estrogen balance, Endocrinology, Volume 143, Issue 12, Pages 4797–4808, doi.org/10.1210/en.2002-220531, 01 December 2002.
  • Featured image credit forum.phish.net.
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Testicular cancer in prenatally DES-exposed men

Environmental Signaling: What Embryos and Evolution Teach Us About Endocrine Disrupting Chemicals, 2001

Abstracts

DES as a model for developmental estrogenization

Studies in our laboratory and others have helped to define a phenotype typical of male mice exposed in utero to DES and other estrogens. The structural or functional changes associated with the phenotype include undescended testes, cysts of the epididymis, prostatic lesions, distended seminal vesicles, retained Müllerian ducts, reduced fertility, and abnormal spermatogenesis (even in a scrotal testis).

In a smaller number of cases, the occurrence of testicular cancers was noted (see 1979 study, 1985 study, 1986 study). The severity of these changes was dose-dependent as were the appearance of all the lesions in the suite. It was subsequently shown that the epididymal cysts were of Müllerian duct origin; it was apparent that the enlarged prostatic utricle was also the Müllerian contribution to the prostate gland.

Features in the human male

Genital tract defects similar to those seen in DES-treated mice were also observed in men whose mothers had taken DES (study).

A group at the University of Chicago reported that DES-exposed men had a higher incidence of undescended (cryptorchid) testes and epididymal cysts than comparable unexposed men. Gill and colleagues (study) went on to confirm and extend these studies and showed, in addition, a higher incidence of hypoplastic testes and abnormal sperm.

In one study reporting testicular cancer in one DES-exposed man, the possibility of cancer of the testis as a result of prenatal exposure to DES was raised by Gill et al. (study). A few other case reports of testicular cancer (seminoma) and epididymal cysts in prenatally DES-exposed men have been reported (study).

References

  • Environmental Signaling: What Embryos and Evolution Teach Us About Endocrine Disrupting Chemicals, Endocrine Reviews, Volume 22, Issue 3, Pages 319–341 doi.org/10.1210/edrv.22.3.0432, 01 June 2001.
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Adenocarcinoma of the rete testis

Diethylstilbestrol-induced lesions of the mouse rete testis, 1986

Abstract

The induction of a lesion resembling carcinoma in the rete testis of male mice provides a useful model for study of the pathogenesis of hormonally induced lesions of the testis and possibly other developmental neoplasms.

The model should be of further use in alerting the clinician to the possibility of rete testis changes in the DES-exposed patient. Also, the extreme rarity of this lesion in both experimental animals and humans has made study of the general cytologic features of this neoplasm difficult; studies of the pathogenesis of the lesion are unknown.

The relatively large number of hyperplasias and adenocarcinomas of the rete testes in DES-treated mice provides new possibilities for such investigations.

While no reports of rete hyperplasia or adenocarcinoma in humans have been attributed to prenatal exposure to DES, three cases of seminoma have been described in prenatally DES-exposed men, suggesting an association of prenatal DES treatment with subsequent development of testicular tumors (1979 study and 1983 study).

A recent report states that rete adenocarcinoma can be misdiagnosed as seminoma, and seminoma must be ruled out before a diagnosis of rete adenocarcinoma can be made. Thus, caution should be taken in diagnosing any testicular lesions associated with prenatal DES exposure.

References

  • Adenocarcinoma of the rete testis. Diethylstilbestrol-induced lesions of the mouse rete testis, The American journal of pathology, NCBI PubMed PMC1888460, 1986 Dec.
  • Featured image apcf.infosite.ust.hk.
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Testicular cancer case in a DES Son

Seminoma and Epididymal Cysts in a Young Man With Known Diethylstilbestrol Exposure In Utero, 1983

Abstract

Exposure of women to diethylstilbestrol in utero has been linked to the development of adenosis and clear cell adenocarcinoma of the vagina.

A variety of male genital tract abnormalities, including epididymal cysts, maldescended testes, hypoplastic testes, varicoceles, and spermatozoal defects, occur with increased incidence in men exposed to diethylstilbestrol in utero.

Testicular tumors occur in adult mice given diethylstilbestrol, and preneoplastic testicular changes have been described in mice exposed prenatally to diethylstilbestrol. The possibility of carcinogenesis has been suggested in diethylstilbestrol-exposed males, but, to our knowledge, until now no case of testicular cancer has been documented in a person exposed in utero to diethylstilbestrol.

We report a seminoma and ipsilateral epididymal cysts in a 28-year-old man with known diethylstilbestrol exposure.

References

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Reproductive tract lesions in male mice exposed prenatally to DES

DES Sons should be further evaluated for latent alterations of the genital tract, 1975

Abstracts

Sixty percent of the male offspring from pregnant mice treated with diethylstilbestrol during gestation were sterile. The affected animals had gonadal changes which included intra-abdominal or fibrotic testes, or both. Additionally, nodular masses in the ampullary region of the reproductive tract were observed in 6 of 24 animals; one of these appeared to be preneoplastic.

… “Eight animals had epididymal cysts; six of these also had testicular lesions.” …

… “In light of these results in rodents, the incidence of cryptorchidism in young boys whose mothers had been treated with DES during gestation may be of clinical importance. Obviously, these offspring should be further evaluated for latent alterations of the genital tract, since changes in the adult male human reproductive tract similar to those we observed in the mouse might be dismissed as secondary to inflammation. Some of these lesions could be important causes of infertility even when viable sperm are produced.” …

References

  • Reproductive tract lesions in male mice exposed prenatally to diethylstilbestrol, Science, NCBI PubMed, PMID: 242076, 1975 Dec 5.
  • Featured image credit quantamagazine.
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Prenatal DES treatment and subsequent development of testicular tumors

Lesions of the rete testis in mice exposed prenatally to diethylstilbestrol, 1985

Abstract

Adenocarcinoma of the rete testis is an exceptionally rare and malignant testicular neoplasm.

Although treatment of pregnant women with diethylstilbestrol (DES) results in reproductive tract abnormalities in their male offspring, increased incidence of testicular tumors has not been verified. However, recently three cases of seminoma have been described in men prenatally exposed to DES, suggesting an association of prenatal DES treatment and the subsequent development of testicular tumors.

This report describes the treatment of outbred pregnant CD-1 mice with DES (100 micrograms/kg) on Days 9 through 16 of gestation and its effects on their male offspring.

In addition to nonmalignant abnormalities such as retained testes which have been reported in men exposed prenatally to DES, lesions resembling adenocarcinoma of the rete testis were seen in prenatally DES-treated mice at 10 to 18 mo of age (11 of 233; 5%). No comparable lesions were seen in 96 age-matched control male mice.

These results suggest an association of prenatal DES exposure and the subsequent development of testicular lesions in the rete testis of mice.

References

  • Lesions of the rete testis in mice exposed prenatally to diethylstilbestrol, Cancer research, NCBI PubMed PMID: 4027990, 1985 Oct.
  • Featured image credit the guardian.
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