Diethylhexyl phthalate exposure impairs follicular development and affects oocyte maturation in the mouse

Zhang, Xifeng; Zhang, Lianjun; Li, Lan; Feng, Yanni; Chen, Bo; Ma, Jin-Mei; Huynh, Evanna; Shi, Qinghua; Felici, Massimo De; Shen, Wei

doi:10.1002/em.21776

Cited by 112 publications

(94 citation statements)

References 59 publications

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“…The hypothalamic-pituitaryovarian axis is involved in the processes of reproductive aging in females, and reprograming of the hypothalamic-pituitary-ovarian axis may also be involved in premature reproductive senescence (Gore et al 2011). All chemicals included in the mixture have been shown to affect either estrogen or androgen actions, and some are capable of interfering with folliculogenesis or follicle health in the ovary (Crellin et al 2001, Adewale et al 2009, Rodríguez et al 2010, Ahn et al 2012, Wang et al 2012, Zhang et al 2013). Thus, direct or indirect mixture effects on the ovaries resulting in early reproductive aging are plausible.…”

Section: Reproductive Aging In Females and Pituitary Gland Changesmentioning

confidence: 99%

Late-life effects on rat reproductive system after developmental exposure to mixtures of endocrine disrupters

et al. 2014

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This study examined late-life effects of perinatal exposure of rats to a mixture of endocrine-disrupting contaminants. Four groups of 14 time-mated Wistar rats were exposed by gavage from gestation day 7 to pup day 22 to a mixture of 13 anti-androgenic and estrogenic chemicals including phthalates, pesticides, u.v.-filters, bisphenol A, parabens, and the drug paracetamol. The groups received vehicle (control), a mixture of all 13 chemicals at 150-times (TotalMix150) or 450-times (TotalMix450) high-end human exposure, or 450-times a mixture of nine predominantly anti-androgenic chemicals (AAMix450). Onset of puberty and estrous cyclicity at 9 and 12 months of age were assessed. Few female offspring showed significantly regular estrus cyclicity at 12 months of age in the TotalMix450 and AAMix450 groups compared with controls. In 19-month-old male offspring, epididymal sperm counts were lower than controls, and in ventral prostate an overrepresentation of findings related to hyperplasia was observed in exposed groups compared with controls, particularly in the group dosed with anti-androgens. A higher incidence of pituitary adenoma at 19 months of age was found in males and females in the AAMix450 group. Developmental exposure of rats to the highest dose of a human-relevant mixture of endocrine disrupters induced adverse effects late in life, manifested as earlier female reproductive senescence, reduced sperm counts, higher score for prostate atypical hyperplasia, and higher incidence of pituitary tumors. These delayed effects highlight the need for further studies on the role of endocrine disrupters in hormone-related disorders in aging humans.

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Section: Reproductive Aging In Females and Pituitary Gland Changesmentioning

confidence: 99%

Late-life effects on rat reproductive system after developmental exposure to mixtures of endocrine disrupters

et al. 2014

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“…Higher concentrations of cadmium inhibited activity of the P450scc gene (Smida, Valderrama, Agostini, Furlan & Chedrese, 2004), inhibited progesterone synthesis (Massanyi, Uhrin, Toman, Kovacik & Biro, 1999;Zhang & Jia, 2007), and facilitated changes in cell morphology and cell death (Smida,et al 2004;Kondoh, Araragi, Sato, Higashimoto, Takiguchi & Sato, 2002). Thus, polluting substances, classified as endocrine disruptors, interfere with the endogenous hormone signaling system, leading to impairment of reproductive health (Caserta et al, 2011;Gupta et al, 2010;Zhang et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

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Gautam¹,

Chaube²

2018

Turk. J. Fish. Aquat. Sci.

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The aim of the present study was to examine comparative effects of different concentrations of heavy metals such as cadmium (Cd), cobalt (Co), lead (Pb) and mercury (Hg) on catfish oocyte maturation and ovulation. Post-vitellogenic oocytes of the catfish H. fossilis were incubated with heavy metals at concentrations of 0.1, 1.0, 10 and 50ng/ml. Translucent follicles without germinal vesicle and opaque follicles with GV were scored after 4, 8, 16, and 24 hr of incubation. Percentage GV breakdown (GVBD) was calculated as an index of oocyte maturation. The results of present investigation suggested that the effect of heavy metals on oocyte maturation and ovulation was in the order of Pb > Hg >Cd>Co. Pb and Hg showed significant increases (P<0.05) in GVBD and ovulation at all concentrations during 4 and 8hr of the incubation. However, there was a dose -dependent decrease at 16 and 24hr. Cd and Co showed decline in GVBD and ovulation at 16 and 24 hr of the incubation. However, mercury and lead showed a stimulatory effect on ovulation at 16 and 24 hr compared to control (P<0.05). Thus, these results suggest that catfish oocytes are differentially influenced by heavy metals and are resistant to them at certain levels.

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“…The sex ratio was not affected. The number of primordial follicles was found to be considerably depleted in the F1 offspring (Zhang et al 2013). …”

Section: Micementioning

confidence: 96%

Di(2‐ethylhexyl) phthalate (DEHP) [MAK Value Documentation, 2016]

Hartwig

Arand²

2017

The MAK‐Collection for Occupational Health and Safety

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The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the developmental toxicity of di(2‐ethylhexyl) phthalate (DEHP) [117‐81‐7]. In 2014, the maximum concentration at the work place (MAK value) of DEHP has been set to 2 mgm for the inhalable fraction. In some studies, a correlation between prenatal DEHP exposure and effects on anogenital distance of male newborns, birth weight and pregnancy duration in humans are found, however, the results are not consistent. Teratogenicity is observed in rats only at maternally toxic doses of 1000 mg/kg bw and day and above, in mice at 91 mg/kg bw and day. NOAELs for teratogenicity are 200 mg/kg bw and day for rats and 44 mg/kg body weight and day for mice, the latter corresponding to 29 mg/m 3 after scaling to a concentration at the work place. In contrast to mouse and marmoset the rat is very sensitive to DEHP effects on the male reproductive organs. From a three generation study the Commission deduces a NOAEL for pre‐ and postnatal developmental toxicity to the male reproductive organs and for fetotoxicity of 46 mg/kg bw and day for rats, corresponding to 54 mg/m 3 after scaling to a concentration at the work place. The reported effects, small testes, reduced absolute weights of testis and epididymis, are considered by the Commission as not being adverse because they do not show correlating consequences for the next generation or dose‐response relationship and changes in relative organ weights and histopathological correlates are not observed. After in utero exposure, germ cell organization, mRNA expression and protein level of StAR („steroidogenic acute regulatory protein“) in testes are affected at 100 mg/kg bw and day and above. These effects resulted in a NOAEL for prenatal developmental effects of the male reproductive organs of 30 mg/kg bw and day for rats, corresponding to 35 mg/m 3 . For mice in prenatal developmental studies a NOAEL for fetotoxicity as well as prenatal developmental toxicity of 48 mg/kg bw and day is derived, corresponding to 32 mg/m 3 . Damage to the embryo or foetus is unlikely when the MAK value is observed and DEHP is classified in Pregnancy Risk Group C.

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Diethylhexyl phthalate exposure impairs follicular development and affects oocyte maturation in the mouse

Cited by 112 publications

References 59 publications

Late-life effects on rat reproductive system after developmental exposure to mixtures of endocrine disrupters

Late-life effects on rat reproductive system after developmental exposure to mixtures of endocrine disrupters

Untitled

Di(2‐ethylhexyl) phthalate (DEHP) [MAK Value Documentation, 2016]

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