Collaborative work on evaluation of ovarian toxicity 12) Effects of 2- or 4-week repeated dose studies and fertility study of indomethacin in female rats

Tsubota, Kenjiro; Kushima, Kiyoshi; Yamauchi, Kenji; Matsuo, Seiki; Saegusa, Tadashi; Ito, Shin; Fujiwara, Michio; Matsumoto, Masahiro; Nakatsuji, Shunji; Seki, Jiro; Oishi, Yuji

doi:10.2131/jts.34.s129

Cited by 14 publications

(7 citation statements)

References 12 publications

(11 reference statements)

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“…Nardo and other scholars [20][21][22][23][24] examined the expression of integrin ανβ3, α4β1 in the endometrium of the fertile women 6 day and 8 days after ovulation, ανβ3, α4β1 was found to be transiently expressed during the implantation window. Meanwhile, the expression of integrin ανβ3 in pregnant women in the implantation window was much higher than that in their non-pregnant counterparts.…”

Section: Discussionmentioning

confidence: 99%

Impact of luteinized unruptured follicles on endometrial receptivity

Yang

Jiang

et al. 2011

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

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This study examined the impact of luteinized unruptured follicle (LUF) on endometrial receptivity. The menstrual cycle of 17 LUF patients (LUF group) and 13 ovulatory women (control group) was monitored by measuring LH level in urine and by ultrasonic examination. An endometrial biopsy at the sixth to tenth day after LH surge was taken in all the patients. The expressions of endometrial ER, PR and integrin ανβ3 were immunohistochemically determined. At the same time, the serum levels of E(2) and P were detected by chemiluminescence. The results exhibited that (1) The mean serum P level in LUF group (7.32±2.56 ng/mL) was significantly lower than that in control group (11.17±3.17 ng/mL) (P<0.01). But there was no significant difference in the mean serum E2 levels between LUF group (179.35±81.60 pg/mL) and the control group (198.58±75.23 pg/mL) (P>0.05); (2) The mean expression intensities of ER, PR in endometrium of LUF group (183.86±2.43, 167.94±3.04) were significantly higher than those in control group (109.35±6.31, 105.98±4.07) (P<0.01); (3) The mean expression intensities of integrin ανβ3 in endomtrium of LUF patients (114.90±11.38) were significantly lower than those in control group (191.34±1.82) (P<0.01); (4) The change profile of integrin ανβ3 expression in the endometrium of LUF patients was in positive relation with serum P level (r=0.77, P<0.01), but bore no significant relationship with serum E(2) level (r=0.01, P>0.05). It was concluded that the depression of serum P levels in LUF patients was closely related to the failure of the down-regulation of ER and PR, and the low expressions of integrin ανβ3 also suggested that the delayed implantation and the impaired endometrial receptivity had impact on embryonic implantation.

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Section: Discussionmentioning

confidence: 99%

Impact of luteinized unruptured follicles on endometrial receptivity

Yang

Jiang

et al. 2011

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

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“…31 Davis et al (1999), 53 Gaytan et al (2006), 66 Greaves (2012), 125 Mattheij and Swarts (1995), 129 Mirsky et al (2011), 172 Sato et al (2009b), 194 Tsubota et al (2009)…”

Section: Morphologymentioning

confidence: 99%

Nonproliferative and Proliferative Lesions of the Rat and Mouse Female Reproductive System

Alison²,

et al. 2014

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The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) Project (www.toxpath.org/inhand.asp) is a joint initiative of the Societies of Toxicological Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP) and North America (STP) to develop an internationally accepted nomenclature for proliferative and nonproliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature for classifying microscopic lesions observed in the female reproductive tract of laboratory rats and mice, with color photomicrographs illustrating examples of some lesions. The standardized nomenclature presented in this document is also available electronically on the internet (http://www.goreni.org/). Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous and aging lesions as well as lesions induced by exposure to test materials. There is also a section on normal cyclical changes observed in the ovary, uterus, cervix and vagina to compare normal physiological changes with pathological lesions. A widely accepted and utilized international harmonization of nomenclature for female reproductive tract lesions in laboratory animals will decrease confusion among regulatory and scientific research organizations in different countries and provide a common language to increase and enrich international exchanges of information among toxicologists and pathologists.

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“…If effects on the small follicles are predicted in the qualitative analysis, a further approach including MOA should be performed. Our validation study also provided very informative evidence that the chemicals related to non-ovulated follicles induced common histopathological changes such as unruptured follicles, unruptured luteinized follicles, luteinized/luteal cysts, expansion of the cumulus oophorus, and cystic corpus lutea Tsubota et al, 2009). When the estrous cycle is normal and no degenerated oocytes are found, distinguishing the corpus luteum with a cavity from a cystic corpus luteum or a luteinized cyst after normal ovulation, More information on these lesions is required.…”

Section: Discussionmentioning

confidence: 76%

“…These present studies suggest that a precise histopathological examination may be able to predict the effect of test articles on female reproductive functions. Reference: Tsubota et al (2009) …”

Section: Di-(2-ethylhexyl) Phthalate (Dehp)mentioning

confidence: 99%

Collaborative work on evaluation of ovarian toxicity by repeated-dose and fertility studies in female rats

Sanbuissho

Yoshida²,

Hisada

et al. 2009

J. Toxicol. Sci.

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-The National Institute of Health Sciences (NIHS) and 18 pharmaceutical companies of the Japan Pharmaceutical Manufacturers Association (JPMA) have conducted a validation study intended to evaluate whether a 2-week repeated general toxicity period with histopathological examination is -ing that it is adequate. Evaluation of ovarian toxicity by comprehensive histopathological examination of the female reproductive organs based on the underlying morphology of a normal cycle of the reproductive tract including the ovary and additional immunohistochemical staining with proliferative cell nuclear antigen (PCNA) to identify small follicles may be a good tool to assess female reproductive function. In the collaborative study, 2-or 4-week repeated dose toxicity studies with ovarian histopathological examinations were conducted. A female fertility study was also conducted to compare the results with those of hormone analogues, primordial follicle damaging agents, metabolite imbalance inducers, and endocrine imbalance inducers. Based on the results, ovarian toxicity could be detected by a careful histopatholgi--female fertility parameters (irregular estrous cycle, pre-implantation loss).

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Collaborative work on evaluation of ovarian toxicity 12) Effects of 2- or 4-week repeated dose studies and fertility study of indomethacin in female rats

Cited by 14 publications

References 12 publications

Impact of luteinized unruptured follicles on endometrial receptivity

Impact of luteinized unruptured follicles on endometrial receptivity

Nonproliferative and Proliferative Lesions of the Rat and Mouse Female Reproductive System

Collaborative work on evaluation of ovarian toxicity by repeated-dose and fertility studies in female rats

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