Prenatal di‐n‐butyl phthalate exposure alters reproductive functions at adulthood in male rats

Giribabu, Nelli; Sainath, S.B.; Reddy, P. Sreenivasula

doi:10.1002/tox.21779

Cited by 36 publications

(38 citation statements)

References 61 publications

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“…These abnormalities are consistent with inhibiting fetal testosterone production (Scott et al, 2009). Moreover, decreases in testicular or serum testosterone levels in juvenile male rats (≤ postnatal days 35) (Shultz et al, 2001;Mylchreest et al, 2002;Fisher et al, 2003;Fisher, 2004) and in adult male rats Wakui et al, 2013Wakui et al, , 2014Giribabu et al, 2014) were described after in utero DBP exposure. Leydig cells (LC) are the cells that synthesize testosterone.…”

Section: Introductionsupporting

confidence: 51%

Retraction: In utero-exposed di(n-butyl) phthalate induce dose dependent, age-related changes of morphology and testosterone-biosynthesis enzymes/associated proteins of Leydig cell mitochondria in rats

Motohashi

Wempe

Mutou³

et al. 2016

J. Toxicol. Sci.

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-Female pregnant Sprague-Dawley rats were intragastrically (ig) administered di(n-butyl) phthalate (DBP) at four doses (0, 10, 50 and 100 mg/kg) during gestation days (GD) 12-21 (n = 5 per group). The age-related morphological changes of Leydig cell mitochondrion (LC-Mt) and testosterone biosynthesis enzymes/associated genes/proteins expression levels were investigated. As compared to the control (no DBP), the 10 mg, and 50 mg DBP dose groups, the 100 mg DBP dose group at weeks 5 and 7 showed a significant amount of small LC-Mt. Thereafter, from weeks 9 to 17, the LC-Mt size and quantity in the100 mg DBP dose group increased and became statistically similar to the other dose groups; hence, dose and time-dependent LC-Mt changes were observed. Throughout the study, the 100 mg DBP dose group had significantly lower testosterone levels. In addition, the 100 mg DBP dose group displayed lower StAR (StAR, steroidogenic acute regulatory protein) and P450scc (CYP11a1, cholesterol side-chain cleavage enzyme) levels at weeks 5 and 7, but they became statistically similar to all other dose groups at weeks 9 to 17; in contrast, the SR-B1 (Sarb1, scavenger receptor class B member 1) levels were similar for all DBP dose groups. The rats in utero 100 mg DBP /kg/day (GD 12-21) exposure results from this study indicate a dose-dependent, age-related morphological change in LC-Mt which are linked to reductions in testosterone biosynthesis genes / proteins expression, specifically StAR and P450scc.

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Section: Introductionsupporting

confidence: 51%

Retraction: In utero-exposed di(n-butyl) phthalate induce dose dependent, age-related changes of morphology and testosterone-biosynthesis enzymes/associated proteins of Leydig cell mitochondria in rats

Motohashi

Wempe

Mutou³

et al. 2016

J. Toxicol. Sci.

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“…Reduction of testosterone level is probably due to the reduction of number of Sertoli cells, since the function and survival of Leydig cells in adulthood is dependent on persistent presence of Sertoli cells [22,23]. Furthermore it has been shown that prenatal exposure of male rat to Di-n-Butyl Phthalate (DBP) (anti-androgen, which reduces androgen level) decreases the activity level of testicular steroidogenic enzymes, as well as testosterone level in adults [16]. Another study demonstrated that prenatal exposure of male rat to testosterone propionate, during days 17-19 of gestation, will lead to reduction of plasma testosterone level during adulthood [10].…”

Section: Discussionmentioning

confidence: 99%

“…Sperm solution preparation were carried out according to the method described by Giribau, N et al [16] with some modification. In brief, animals were anesthetized by intraperitoneal injection (i.p) of pentobarbital sodium (P3761, 5mg, Sigma, USA) dissolved in normal saline 0.9% (60 mg/kg body weight), immediately after anesthesia; the right epididymis was removed, weighed and then transferred to petri dish containing 2 ml of normal saline, caudal portion of epididymis isolated, split with needle then 20 µl semen removed from caudal portion of epididymis.…”

Section: Methodsmentioning

confidence: 99%

“…Evaluation of the sperm motility, was carried out according to the method described by Giribau, N et al and Toledo, F.C et al [16,17] with some modification. In brief, immediately after preparation of sperm solution, one drop of sperm solution was placed on Neubauer Chamber slide and 10 fields were examined, under a light microscope (100 x magnification).…”

Section: Methodsmentioning

confidence: 99%

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Prenatal Testosterone Exposure Worsen the Reproductive Performance of Male Rat at Adulthood

et al. 2013

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The reproductive system is extremely susceptible to environmental insults, for example exogenous steroids during gestational development and differentiation. Experimental induction of androgen excess during prenatal life in female animal models reprograms their reproductive physiology, however the fetal programming of the male reproductive system by androgen excess has not been well studied. We aimed to determine the effect of prenatal exposure of two different doses of testosterone on different gestational days, on the male reproductive system using a rat model. Sixteen pregnant rats were randomly divided into two experimental groups and two control groups. Experimental group І were subcutaneously injected with 3 mg free testosterone on gestational days 16-19 and its controls received solvent for that time; experimental group П were subcutaneously injected with 20 mg free testosterone on day 20 of gestational period and its controls received solvent at the same time. The reproductive system morphology and function of 32 male offspring of these study groups were compared at days 6-30-60 of age and after puberty. The anogenital distance of the male offspring of both experimental groups had no significant differences on the different days of measurement, compared with controls. In the offspring of experimental group І, the testes weight, number of Sertoli, Spermatocyte and Spermatid cells, sperm count and motility and the serum concentration of testosterone after puberty were significantly decreased; except for reduction of sperm motility (p< 0.01), the other effects were not observed in the offspring of experimental group ІІ. In summary, our data show that prenatal exposure of male rat fetuses to excess testosterone disrupted reproductive function, an effect highly dependent on the time, duration and level of exposure. It seems that the reproductive system in individuals exposed to high levels of androgens during fetal life should be evaluated at puberty and likely to be treated.

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“…This “phthalate syndrome” is characterized by malformations in the male reproductive organs, retention of nipples, and reduced anogenital distance (AGD) [11, 12]. Moreover, gestational exposures to different phthalates have been shown to reduce fertility in male rodents by decreasing steroidogenic capacity, sperm quality and quantity, and sexual behaviors [13–16]. However, the effects of prenatal phthalate exposure on female reproduction in the offspring are less extensively studied.…”

Section: Introductionmentioning

confidence: 99%

Prenatal exposure to an environmentally relevant phthalate mixture disrupts reproduction in F1 female mice

Zhou

Gao

Flaws

2017

Toxicology and Applied Pharmacology

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Phthalates are used in a large variety of products, such as building materials, medical devices, and personal care products. Most previous studies on the toxicity of phthalates have focused on single phthalates, but it is also important to study the effects of phthalate mixtures because humans are exposed to phthalate mixtures. Thus, we tested the hypothesis that prenatal exposure to an environmentally relevant phthalate mixture adversely affects female reproduction in mice. To test this hypothesis, pregnant CD-1 dams were orally dosed with vehicle (tocopherol-stripped corn oil) or a phthalate mixture (20 and 200 μg/kg/day, 200 and 500 mg/kg/day) daily from gestational day 10 to birth. The mixture was based on the composition of phthalates detected in urine samples from pregnant women in Illinois. The mixture included 35% diethyl phthalate, 21% di(2-ethylhexyl) phthalate, 15% dibutyl phthalate, 15% diisononyl phthalate, 8% diisobutyl phthalate, and 5% benzylbutyl phthalate. Female mice born to the exposed dams were subjected to tissue collections and fertility tests at different ages. Our results indicate that prenatal exposure to the phthalate mixture significantly increased uterine weight and decreased anogenital distance on postnatal days 8 and 60, induced cystic ovaries at 13 months, disrupted estrous cyclicity, reduced fertility-related indices, and caused some breeding complications at 3, 6, and 9 months of age. Collectively, our data suggest that prenatal exposure to an environmentally relevant phthalate mixture disrupts aspects of female reproduction in mice.

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Prenatal di‐n‐butyl phthalate exposure alters reproductive functions at adulthood in male rats

Cited by 36 publications

References 61 publications

Retraction: <i>In utero</i>-exposed di(<i>n</i>-butyl) phthalate induce dose dependent, age-related changes of morphology and testosterone-biosynthesis enzymes/associated proteins of Leydig cell mitochondria in rats

Retraction: <i>In utero</i>-exposed di(<i>n</i>-butyl) phthalate induce dose dependent, age-related changes of morphology and testosterone-biosynthesis enzymes/associated proteins of Leydig cell mitochondria in rats

Prenatal Testosterone Exposure Worsen the Reproductive Performance of Male Rat at Adulthood

Prenatal exposure to an environmentally relevant phthalate mixture disrupts reproduction in F1 female mice

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