Impact of dietary exposure to methoxychlor, genistein, or diisononyl phthalate during the perinatal period on the development of the rat endocrine/reproductive systems in later life

Masutomi, Naoya; Shibutani, Makoto; Takagi, Hironori; Uneyama, Chikako; Takahashi, Noriyuki; Hirose, Masao

doi:10.1016/s0300-483x(03)00269-5

Cited by 120 publications

(81 citation statements)

References 37 publications

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“…On the other hand, the reason why the effects of the chemicals were not dose-dependent is currently unclear, but similar non-dose-dependent effect of DBP has been reported by others (Masutomi et al, 2003). DBP at 200 and 2,000 ppm decreased ejaculation frequency, while that at 10,000 ppm increased ejaculation frequency and shortened PEI, without affecting mount and intromission frequency.…”

Section: Effects Of Perinatal Exposure On Female Reproductive Functionsupporting

confidence: 66%

“…This was also demonstrated in the --659 present study. Mylchreest et al (1998) and Masutomi et al (2003) observed that perinatal exposure to DBP or DINP did not affect estrous cyclicity after maturation. Similarly, in the present study, irregular estrous cycles were not observed in rats perinatally exposed to DBP and DINP as well as DEHA.…”

Section: Effects Of Perinatal Exposure On Female Reproductive Functionmentioning

confidence: 98%

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Effects of Phthalate/Adipate Esters Exposure during Perinatal Period on Reproductive Function after Maturation in Rats

Yamanouchi

Nishihara

2006

Journal of Animal Science and Technology

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Section: Effects Of Perinatal Exposure On Female Reproductive Functionsupporting

confidence: 66%

Section: Effects Of Perinatal Exposure On Female Reproductive Functionmentioning

confidence: 98%

Effects of Phthalate/Adipate Esters Exposure during Perinatal Period on Reproductive Function after Maturation in Rats

Yamanouchi

Nishihara

2006

Journal of Animal Science and Technology

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“…Injection of MXC (8-64 mg/kg per day) in adult mice for 20 days did not change the serum FSH levels or levels of the FSH receptor in the ovary (Borgeest et al 2004). In addition, feeding MXC (24-1200 ppm) to pregnant rats between embryonic day 15 (E15) and P10 does not affect the size of the sexually dimorphic nucleus of the pre-optic area of the hypothalamus in the female offspring (Masutomi et al 2003). On the other hand, perinatal (E15-P10) exposure to MXC has been reported to inhibit serum LH levels in adult female rats (Suzuki et al 2004).…”

Section: Discussionmentioning

confidence: 94%

Early postnatal methoxychlor exposure inhibits folliculogenesis and stimulates anti-Mullerian hormone production in the rat ovary

Uzumcu¹,

Kühn²,

Marano³

et al. 2006

Journal of Endocrinology

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Methoxychlor [1,1,1-trichloro-2,2-bis(4-methoxyphenyl) ethane; MXC] is a chlorinated hydrocarbon pesticide commonly used in the United States as a replacement for DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane]. While MXC is a weak estrogenic compound, its more active, major metabolite [2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane; HPTE] shows estrogenic, anti-estrogenic, or anti-androgenic properties depending on the receptor subtype with which it interacts. Anti-Mullerian hormone (AMH) is a paracrine factor that suppresses initial follicle recruitment in the ovary. Studies have shown the effects of exposure to MXC on adult ovarian morphology and function. However, the effect of exposure to MXC at an early postnatal stage on pre-pubertal follicular development and ovarian AMH production has not been studied. Around postnatal day (P) 4, most of the primordial follicular assembly in rats is complete, and a large number of primordial follicles transition into the primary follicle stage, a process that is inhibited by estrogen. The objective of this study was to examine the effect of early postnatal (P3-P10) MXC exposure on ovarian morphology and size, follicle number, and AMH production in the pre-pubertal (P20) rat ovary and to investigate the effect of HPTE on AMH production in immature rat granulosa cells in vitro. Female rats were injected (s.c.) daily with vehicle (control) or 1, 10, 50, 100, or 500 mg MXC/kg per day (referred to here as 1MXC, 10MXC, and so forth.) between P3 and P10. On P20, uterine and ovarian weights were determined, ovarian histology was examined, and follicles were counted and classified into primordial, primary, secondary, pre-antral, or antral stages using the two largest serial sections at the center of the ovary. Ovarian AMH production was examined using immunohistochemistry and western blot analysis. The effect of HPTE (0 . 5-25 mM) on AMH production in cultured immature rat granulosa cells was determined by western blot analysis. Ovarian weight was reduced by 50, 100, and 500MXC (P!0 . 01). MXC treatment inhibited folliculogenesis. Both 100 and 500MXC had a reduced number of antral follicles (P!0 . 05) with a concomitant increase in pre-antral follicles (P!0 . 05). Follicle numbers were not significantly affected by 1, 10, or 50MXC. Total follicle number and the number of primordial, primary, or secondary stage follicles were not significantly different in all treatment groups. Immunohistochemistry showed that MXC-treated ovaries had more AMH-positive follicles with stronger AMH immunostaining.Western blot analysis showed that AMH production was 1 . 6G 0 . 2, 1 . 85G0 . 6, and 2 . 2G0 . 5 times higher in the 50, 100, and 500MXC ovaries as compared with the control ovaries respectively (P!0 . 05). Granulosa cells treated with 1 or 5 mM HPTE had significantly greater AMH production (P!0 . 05).These results demonstrate that MXC inhibits early ovarian development and stimulates AMH production directly in the rat ovary. In addition, HPTE was shown to stimulate AMH producti...

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“…Presumably these effects are due to the actions of phytoestrogens on estrogen receptors, possibly as anti-estrogens [87]. It should be noted that Masutomi et al did not report any effects of neontal genistein and xenoestrogens (methoxychlor, phthalates) on SDN-POA volume in early adulthood [95]; differences in results may be attributable to the age of analyses, and doses and modes of administration of the EDCs.…”

Section: Effects Of Perinatal Edcs On the Avpv And Sdn-poa Morphologymentioning

confidence: 97%

Developmental programming and endocrine disruptor effects on reproductive neuroendocrine systems

Gore¹

2008

Frontiers in Neuroendocrinology

230

122

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The ability of a species to reproduce successfully requires the careful orchestration of developmental processes during critical time points, particularly the late embryonic and early postnatal periods. This article begins with a brief presentation of the evidence for how gonadal steroid hormones exert these imprinting effects upon the morphology of sexually differentiated hypothalamic brain regions, the mechanisms underlying these effects, and their implications in adulthood. Then, I review the evidence that aberrant exposure to hormonally-active substances such as exogenous endocrine-disrupting chemicals (EDCs), may result in improper hypothalamic programming, thereby decreasing reproductive success in adulthood. The field of endocrine disruption has shed new light on the discipline of basic reproductive neuroendocrinology through studies on how early life exposures to EDCs may alter gene expression via non-genomic, epigenetic mechanisms, including DNA methylation and histone acetylation. Importantly, these effects may be transmitted to future generations if the germline is affected via transgenerational, epigenetic actions. By understanding the mechanisms by which natural hormones and xenobiotics affect reproductive neuroendocrine systems, we will gain a better understanding of normal developmental processes, as well as to develop the potential ability to intervene when development is disrupted.

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Impact of dietary exposure to methoxychlor, genistein, or diisononyl phthalate during the perinatal period on the development of the rat endocrine/reproductive systems in later life

Cited by 120 publications

References 37 publications

Effects of Phthalate/Adipate Esters Exposure during Perinatal Period on Reproductive Function after Maturation in Rats

Effects of Phthalate/Adipate Esters Exposure during Perinatal Period on Reproductive Function after Maturation in Rats

Early postnatal methoxychlor exposure inhibits folliculogenesis and stimulates anti-Mullerian hormone production in the rat ovary

Developmental programming and endocrine disruptor effects on reproductive neuroendocrine systems

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