Neonatal Exposure to Di(n-Butyl) Phthalate (Dbp) Alters Male Reproductive-Tract Development

Kim, Hyung Sik; Kim, Tae Sung; Shin, Jae‐Ho; Moon, Hyun Ju; Kang, Il Hyun; Kim, In Young; Oh, Ji Young; Han, Soon Young

doi:10.1080/15287390490514859

Cited by 76 publications

(47 citation statements)

References 39 publications

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“…A lot of studies were dedicated to the influence of xenoestrogens on the male reproductive system during fetal period of life [9,16] and only few dealt with the postnatal development [17][18][19]. An objective of our study was to assess the influence of different doses of xenoestrogens: DES and ZEA on testicular development and quantitative aspects of spermatogenesis in pubertal rats and to compare results with the effect of natural estrogen -17β-estradiol (E).…”

Section: Introductionmentioning

confidence: 99%

Xenoestrogens diethylstilbestrol and zearalenone negatively influence pubertal rat's testis.

Filipiak

Walczak-Jędrzejowska²,

Oszukowska³

et al. 2010

Folia Histochem Cytobiol.

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Abstract:The aim of this study was to assess the impact of xenoestrogens: diethylstilbestrol (DES) and zearalenone (ZEA) on rat's pubertal testis and to compare it with the effect of natural estrogen -17β-estradiol (E). Male Wistar rats were daily, subcutaneously injected at 5 th -15 th postnatal days (p.d.) with E (1.25 or 12.5 μg) or DES (1.25 or 12.5 μg) or ZEA (4 or 40 μg) or vehicle. At 16 th p.d. testes were dissected, weighted, and paraffin embedded. Following parameters were assessed: diameter and length of seminiferous tubule, numbers of spermatogonia A+intermediate+B (A/In/B), preleptotene spermatocytes (PL), leptotene+zygotene+pachytene spermatocytes (L/Z/PA) and Sertoli cells per testis. Testes weight, seminiferous tubule diameter and length were decreased by both doses of E, DES and ZEA. DES effect was the strongest, but its influence on testis weight and seminiferous tubule length, on the contrary to E and ZEA, was not dose-dependent. Similarly, DES in both doses had the most severe negative impact on the number of germ and Sertoli cells. The negative influence of E on germ cells was less pronounced. The negative effect of ZEA was seen only after administration of the higher dose on spermatogonia number, while DES and E decreased A/In/B number more evidently. Sertoli cell number were decreased after both doses of E. ZEA40 decreased Sertoli cell number while ZEA4 had no effect. Conclusion: exposure of prepubertal male rat to DES has the strongest detrimental effect on the developing testis in comparison to E and ZEA. Both, E and DES, decreased number of germ and Sertoli cells, diminished seminiferous tubule diameter, length and testis weight. ZEA had much more weaker effect than the potent estrogens.

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Section: Introductionmentioning

confidence: 99%

Xenoestrogens diethylstilbestrol and zearalenone negatively influence pubertal rat's testis.

Filipiak

Walczak-Jędrzejowska²,

Oszukowska³

et al. 2010

Folia Histochem Cytobiol.

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“…The doses of DBP which have been proved by other authors [3,6,22,23] to have negative effects on reproductive parameters were extremely high, and exceeded the DBP estimated environmental exposure. The estimated daily exposure of an average person to DBP varies widely according to different studies; it approximates to 0.007-7 μg/kg/b.w.…”

Section: Discussionmentioning

confidence: 90%

“…The majority of reports on DBP's influence on the male reproductive tract describe treatment with doses of around 500 mg/kg b.w. on pregnant females [3,22,23] or about 1 g/kg b.w (20 mg/animal) on neonatal rats [6] to cause adverse effects. To the best of our knowledge, there have been no studies examining the influence of DBP in doses of 1 and 10 mg/kg b.w.…”

Section: Discussionmentioning

confidence: 99%

“…(reflecting the dose of 20 and 200 μg/animal used in the presented study) on testicular development. Based on the previous studies where a DBP dose of 5 mg/animal did not exert any biological effect on analyzed parameters (testis weight, serum testosterone level, AR and ERb concentrations) [6], no negative impact of such low doses should be expected. However, a study by Ge et al [7] suggested that besides the negative impact of high doses, the stimulatory effect of low phthalate doses on the onset of puberty can also be observed, as when rats have been treated with a dose of 10 mg/kg b.w.…”

Section: Discussionmentioning

confidence: 99%

“…The only study to have examined DBP's influence on the prepubertal rat testis, performed by Kim et al [6], showed that a daily dose of 20 mg/animal administered from the 5 th to the 14 th day of life caused reduction of testis weight and the disruption of androgen receptor (AR) and estrogen receptor (ER) concentration in the testes of rats aged 31 days and 42 days. The authors attributed the antiandrogenic activity to the negative influence of DBP rather than to the positive influence of estrogen.…”

Section: Introductionmentioning

confidence: 99%

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Di(n-butyl) phthalate has no effect on the rat prepubertal testis despite its estrogenic activity in vitro

Filipiak¹,

Walczak-Jędrzejowska²,

Krupiński³

et al. 2012

Folia Histochem Cytobiol.

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Abstract:The aim of this study was to assess the impact of di(n-butyl) phthalate (DBP) on the rat's prepubertal testis. Male Wistar rats were given daily subcutaneous injections with DBP (20 or 200 μg) or a vehicle from the 5 th to the 15 th postnatal day (pd). On the 16 th pd, the rats were euthanized, and the testes were dissected, weighed, and paraffin embedded. The blood was collected to determine the serum levels of testosterone (T), estradiol (E) and FSH. The following parameters were assessed in the testis sections: diameter and length of seminiferous tubules (st), numbers of spermatogonia A + intermediate + B (A/In/B), preleptotene spermatocytes (PL), leptotene + zygotene + pachytene spermatocytes (L/Z/PA) and Sertoli cells per testis, percentage of st containing gonocytes or pachytene spermatocytes or lumen. An estrogenicity in vitro test was performed by means of a transgenic yeast strain expressing human estrogen receptor alpha. At both doses, DBP had no influence on testis and seminal vesicle weight, st diameter and length, number of germ and Sertoli cells per testis, percentage of st containing gonocytes or pachytene spermatocytes or lumen. DBP did not change E, T or FSH serum levels. The in vitro yeast screen showed that DBP was a weak estrogenic compound, approximately six to seven orders of magnitude less potent than 17b-estradiol. In conclusion, exposure of a rat to DBP in doses 100 or 1,000-fold higher than a Tolerable Daily Intake for humans had no effect on its testicular development. (Folia Histochemica

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Endocrine Disruptors

Kougias,

Kundu

2023

Patty's Toxicology

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Endocrine disruption is a relatively new field of study, as endocrine disruptors were not formally acknowledged by regulatory agencies until 1996. Over the years, many federal and international regulatory agencies and professional associations have provided varying terminology and classifications; however, in general, exposure to endocrine disruptors, or endocrine‐disrupting chemicals (EDCs), at environmentally relevant doses results in adverse effects consequent to interfering with endocrine function. Apart from minor nomenclature disagreements, there are challenges and limitations to this field, as EDC classification criteria can vary substantially in considering evidence for a biologically plausible causal relationship between the endocrine activity and the induced adverse effect. Accordingly, international consensus for unambiguous designation of EDCs is lacking. Therefore, this chapter will not attempt to resoundingly identify all known or suspected EDCs; rather, the objective of this chapter is to first provide historical context to chemical regulation, including on endocrine disruption and its development as a field, and then follow with a review of the health implications, which highlights some fundamental concepts of endocrine disruption and incorporates a tale of the infamous public health disaster resulting from prescribing pregnant women diethylstilbestrol (DES), a potent synthetic estrogen. The current testing guidelines and standards for EDCs are also reviewed, demonstrating the restricted focus on canonical endocrine disruption that is characterized by nuclear hormone receptor‐based activity and the estrogenic, androgenic, thyroidal, and steroidogenic (EATS) modalities. To end, some of the more recently regulated EDCs, particularly bisphenol A and phthalates, as well as other ubiquitous EDCs, like phytoestrogens and flame retardants, are reviewed.

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Neonatal Exposure to Di(n-Butyl) Phthalate (Dbp) Alters Male Reproductive-Tract Development

Cited by 76 publications

References 39 publications

Xenoestrogens diethylstilbestrol and zearalenone negatively influence pubertal rat's testis.

Xenoestrogens diethylstilbestrol and zearalenone negatively influence pubertal rat's testis.

Di(n-butyl) phthalate has no effect on the rat prepubertal testis despite its estrogenic activity in vitro

Endocrine Disruptors

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