Experimental Model to Study Reproductive Toxicity of Chemicals using Induced Ovulation in Immature F344 Rats.

Sekiguchi, Soichiro; Ito, Shin; Honma, Takeshi

doi:10.2486/indhealth.41.287

Cited by 11 publications

(13 citation statements)

References 11 publications

(22 reference statements)

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“…It has long been known that follicles of 4-to 8-week-old lambs are particularly sensitive to gonadotropin administration using protocols developed for adult animals (Worthington & Kennedy 1979, Armstrong et al 1994, Ptak et al 1999. On the other hand, ovarian stimulation has proved to be a simple and useful tool to detect alterations in rodent reproductive organs and to study likely changes in the mechanisms of hormonal action induced by certain substances (Sekiguchi et al 2003). In this study, we applied a protocol of oFSH-ovarian stimulation in prepubertal lambs and demonstrated that early postnatal exposure of BPA or DES impaired the ovarian functional response to oFSH treatment.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the use of this procedure to investigate female reproductive toxicity certainly simplifies and reduces the time-consuming properties of routine experiments (such as evaluation of the estrous cycle, spontaneously ovulated ova, etc.) and allows the development of toxicological procedures to elucidate the mechanisms of toxicants, which impair the female reproductive system (Sekiguchi et al 2003). Based on these reasons, we selected the ovarian response to an exogenous gonadotropin treatment as a tool to study ovarian functionality in immature lambs neonatally exposed to xenoestrogens.…”

Section: Introductionmentioning

confidence: 99%

“…One of the most widely used ovarian endocrine-disruption models is the immature animal primed with exogenous hormones (Petroff et al 2000, Sekiguchi et al 2003). This animal model allows detecting dysfunctions in the development of growing follicles that will reach the pre-ovulatory stage, the number of corpora lutea and ova shed, and the levels of ovarian hormones.…”

Section: Introductionmentioning

confidence: 99%

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Neonatal exposure to xenoestrogens impairs the ovarian response to gonadotropin treatment in lambs

Rivera¹,

Varayoud²,

Rodríguez³

et al. 2015

Reproduction

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Bisphenol A (BPA) and diethylstilbestrol (DES) are xenoestrogens, which have been associated with altered effects on reproduction. We hypothesized that neonatal xenoestrogen exposure affects the ovarian functionality in lambs. Thus, we evaluated the ovarian response to exogenous ovine FSH (oFSH) administered from postnatal day 30 (PND30) to PND32 in female lambs previously exposed to low doses of DES or BPA (BPA50: 50 mg/kg per day, BPA0.5: 0.5 mg/kg per day) from PND1 to PND14. We determined: i) follicular growth, ii) circulating levels of 17b-estradiol (E 2 ), iii) steroid receptors (estrogen receptor alpha, estrogen receptor beta, and androgen receptor (AR)) and atresia, and iv) mRNA expression levels of the ovarian bone morphogenetic protein (BMPs) system (BMP6, BMP15, BMPR1B, and GDF9) and FSH receptor (FSHR). Lambs neonatally exposed to DES or BPA showed an impaired ovarian response to oFSH with a lower number of follicles R2 mm in diameter together with a lower number of atretic follicles and no increase in E 2 serum levels in response to oFSH treatment. In addition, AR induction by oFSH was disrupted in granulosa and theca cells of lambs exposed to DES or BPA. An increase in GDF9 mRNA expression levels was observed in oFSH-primed lambs previously treated with DES or BPA50. In contrast, a decrease in BMPR1B was observed in BPA0.5-postnatally exposed lambs. The modifications in AR, GDF9, and BMPR1B may be associated with the altered ovarian function due to neonatal xenoestrogen exposure in response to an exogenous gonadotropin stimulus. These alterations may be the pathophysiological basis of subfertility syndrome in adulthood.Reproduction (2015) 149 645-655

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Neonatal exposure to xenoestrogens impairs the ovarian response to gonadotropin treatment in lambs

Rivera¹,

Varayoud²,

Rodríguez³

et al. 2015

Reproduction

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“…Co., Ltd., Japan) at a dose of 15 iu in 0.15 ml saline injected intramuscularly (im) at 25 d of age to intact females and at 28 d of age to hypox females followed by 15 iu hCG (Teikoku Hormone) in 0.15 ml saline injected intraperitoneally (ip) at 27 or 30 d of age, 56 or 72 h after the eCG injection. All rats were sacrificed by decapitation at 28 or 31 d of age, at 72 h after the eCG injection 16) , and the ovaries and uteri were weighed after removing the fat and connective tissue. Ova shed into oviducts were collected and counted 16) .…”

Section: Animals and Experimental Designsmentioning

confidence: 99%

“…In our previous study, subcutaneous injections of 500 mg/kg of DEHP administered to immature F344 rats tended to suppress superovulation induced by a single injection of eCG 16) . In the present study, in order to determine the exact effects of DEHP on reproductive function, the ability of eCG and hCG to induce superovulation in DEHP-treated rats was estimated, and we also investigated whether thyroid hormone is involved in the ovarian toxicity of DEHP.…”

Section: Introductionmentioning

confidence: 99%

Involvement of Thyroxine in Ovarian Toxicity of Di-(2-ethylhexyl) Phthalate

Sekiguchi¹,

Ito²,

Suda³

et al. 2006

Ind Health

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The compound 2-bromopropane possesses reproductive toxicity in male and female humans 1,2) . We showed that an injection of 2-bromopropane or exposure to 1,2-dichloropropane significantly decreased the number of spontaneously ovulated ova and delayed estrous cycle in female F344 rats 3,4) . The number of ovulated ova during superovulation induced by equine chorionic gonadotropin (eCG) and human chorionic gonadotropin (hCG) in mice is significantly reduced by 2-bromopropane 5) . Thus, ovulation is a significant marker that can be used to detect reproductive toxicity in female animals. Some studies have examined the influence of chemicals on the murine ovary in vivo and in vitro by using ovulation induced by eCG and hCG in immature female rats [6][7][8][9] .Di-(2-ethylhexyl) phthalate (DEHP) is generally used as plasticizer of vinyl products, and it exhibits ovarian toxicity after short-term administration in rats. A study in vivo by Davis et al. 10) showed that consecutive daily doses of 2,000 mg/kg of DEHP suppressed or delayed ovulation with a concomitant significant decrease in serum estradiol-17 β (E 2 ). A study in vitro found that mono-(2-ethylhexyl) phthalate (MEHP), an active metabolite of DEHP, decreases the levels of E 2 converted from testosterone (T) in incubation medium 11) , and also those of mRNA for aromatase that synthesizes E 2 from T 12) . These finding suggest that the inhibiting effect on ovulation is caused by suppression of E 2 synthesis. In Abstract: Forced ovulation induced by the administration of exogenous gonadotropin is a useful marker for studying the ovarian toxicity of chemicals in experimental animals. We examined the toxicity of di-(2-ethylhexyl) phthalate (DEHP) in the ovaries of immature F344 female rats. Superovulation was induced by injections of equine chorionic gonadotropin (eCG) and human chorionic gonadotropin (hCG) in rats dosed with 125, 250, 500, 1,000 or 2,000 mg/kg body weight of DEHP for 4 consecutive days. The number of ova shed during superovulation significantly decreased in rats treated with DEHP at 500 mg/kg as compared with control, but no changes were observed in the number of ova in groups given other doses of DEHP. In control rats treated with olive oil, hypophysectomy reduced significantly the number of ovulated ova. When 2,000 mg DEHP was given to hypophysectomized (hypox) rats, the number of ova in the hypox group was significantly smaller than that in the intact group administered with the same doses of DEHP. In contrast, the numbers of ova of the intact and hypox groups did not significantly differ in rats given 500 mg DEHP. The levels of circulating thyroxine (T 4 ) were significantly decreased by 2,000 mg DEHP in intact rats, and a tendency for T 4 to decrease in T 4 was also observed in hypox rats given 2,000 mg DEHP. These results suggest that daily administration of 500 mg DEHP suppressed superovulation in immature F344 rats by disrupting the hypothalamic-pituitary-ovarian axis in a manner similar to that of hypophysectomy. Decreased circulating ...

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The effects of endocrine‐disrupting chemicals on ovarian‐ and ovulation‐related fertility outcomes

Land

Miller

Fugate

et al. 2022

Molecular Reproduction Devel

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Exposure to endocrine‐disrupting chemicals (EDCs) is unavoidable, which represents a public health concern given the ability of EDCs to target the ovary. However, there is a large gap in the knowledge about the impact of EDCs on ovarian function, including the process of ovulation. Defects in ovulation are the leading cause of infertility in women, and EDC exposures are contributing to the prevalence of infertility. Thus, investigating the effects of EDCs on the ovary and ovulation is an emerging area for research and is the focus of this review. The effects of EDCs on gametogenesis, uterine function, embryonic development, and other aspects of fertility are not addressed to focus on ovarian‐ and ovulation‐related fertility issues. Herein, findings from epidemiological and basic science studies are summarized for several EDCs, including phthalates, bisphenols, per‐ and poly‐fluoroalkyl substances, flame retardants, parabens, and triclosan. Epidemiological literature suggests that exposure is associated with impaired fecundity and in vitro fertilization outcomes (decreased egg yield, pregnancies, and births), while basic science literature reports altered ovarian follicle and corpora lutea numbers, altered hormone levels, and impaired ovulatory processes. Future directions include identification of the mechanisms by which EDCs disrupt ovulation leading to infertility, especially in women.

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Experimental Model to Study Reproductive Toxicity of Chemicals using Induced Ovulation in Immature F344 Rats.

Cited by 11 publications

References 11 publications

Neonatal exposure to xenoestrogens impairs the ovarian response to gonadotropin treatment in lambs

Neonatal exposure to xenoestrogens impairs the ovarian response to gonadotropin treatment in lambs

Involvement of Thyroxine in Ovarian Toxicity of Di-(2-ethylhexyl) Phthalate

The effects of endocrine‐disrupting chemicals on ovarian‐ and ovulation‐related fertility outcomes

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