Influence of high‐dose methotrexate therapy on the primordial follicles of the mouse ovary

Göl, Mert; Saygılı, Uğur; Koyuncuoğlu, Meral; Uslu, Turhan

doi:10.1111/j.1447-0756.2008.00945.x

Cited by 23 publications

(13 citation statements)

References 19 publications

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“…In the present study, evaluation of ovaries was carried out to examine as many follicles and corpus luteum as possible. Our results indicate MTX as an ovarian toxicant and correspond well with previous reports of disruption of follicles and ovarian cells by alkylating agents 85, 96, 118…”

Section: Discussionsupporting

confidence: 92%

“…Our results unambiguously substantiate the hypothesis that the fast proliferating cells in the female reproductive tissues are altered by MTX. The ability of alkylating agents to disrupt morphogenesis of ovary has previously been reported 20, 85. However, to the best of our knowledge this is the first report to mention the use of LCN and withdrawal of MTX treatment as mitigating factors.…”

Section: Discussionmentioning

confidence: 66%

“…The few reports that exist either suggest the ability of LCN to rescue MTX in tumour86 or withdrawal treatment in juvenile arthritis models 87. Recently, the effects of MTX treatment toxicity and intervention of folinic acid have been reported 12, 18, 20, 85. Interestingly, there exists various degrees of discrepancies between recent reports on effects of MTX in the reproductive endocrine system 88, 89.…”

Section: Discussionmentioning

confidence: 99%

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Effect of methotrexate and leucovorin on female reproductive tract of albino rats

Karri

Vanithakumari

2010

Cell Biochem. Funct.

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Methotrexate (MTX) an antifolate drug and leucovorin its antidote, are used in the treatment of both neoplastic and non-neoplastic diseases in young women. We hypothesize that MTX treatment might comprise a deleterious effect on fast proliferating reproductive cells, an unavoidable and unwanted side effect. MTX given dose dependently to rats for 20 days prevented vaginal cyclicity and caused a reduction in serum progesterone and estradiol. External morphology of reproductive tract displayed thinning of organs and reduction in their weights. To reveal mechanism of MTX action, we examined the histology of ovary, oviduct, uterus, cervix and vagina. Results suggested that in a dose-dependent fashion MTX restrained preantral and antral follicular growth in ovary. Epithelium and stroma of oviduct, uterus, cervix and vagina were disrupted and lost their normal structures. Such alterations in ovarian function raised serum follicle stimulating hormone, luteinizing hormonal profiles. Expression of steroidogenic acute regulatory protein and P450 cholesterol side chain cleavage gene, which are both essential for steroidogenesis, markedly decreased in ovary upon MTX treatment. Total RNA, DNA and protein concentrations, glucose 6 phosphate dehydrogenase, lactate dehydrogenase and alkaline phosphatase enzyme activities in ovary were distinctly altered. Leucovorin supplementation and withdrawal of the treatment, improved MTX caused effects partially. These results for the first time indicate that the malfunction of female reproductive organs by MTX treatment in young women is not only correlated to the disrupted circulating levels of hormones and histoarchitecture of tissues but also discrepancies in steroidogenic genes and hormone regulated enzyme activities in ovary.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 99%

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Effect of methotrexate and leucovorin on female reproductive tract of albino rats

Karri

Vanithakumari

2010

Cell Biochem. Funct.

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“…There is a profound lack of human studies looking into the relationship between cumulative MTX dose and ovarian reserve. Murine studies have identified damage to the primordial follicles following MTX therapy [4,18]. The underlying mechanism of MTX-related ovarian damage is poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Effects of Methotrexate Therapy on the Levels of Gonadotropic Hormones in Rheumatoid Arthritis Patients of Reproductive Age

Kyaw¹,

Sakthiswary²,

Amelia³

et al. 2020

Cureus

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“…Wolff, Bern oder auch die moderneren Biologikatherapien haben eher keinen negativen Einfluss, wie sich v. a. im Tiermodell gezeigt hat [5,6,7].…”

Section: Cyclophosphamidtherapieunclassified

Fertilitätsprotektion bei rheumatologischen Erkrankungen

Henes

Schmalzing

et al. 2012

Gynäkologische Endokrinologie

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In Deutschland leiden etwa 2% der Erwachsenen an einer Autoimmunerkrankung (AID; [1]). Fast alle AID betreffen deutlich häufiger Frauen alsMänner. In einigen Fällen ist bei diesen Erkrankungen eine immunsuppressive Therapie mit dem ovarschä-digenden Medikament Cyclophosphamid (CYC) notwendig. Auch diese Patientinnen sollten daher über die Möglichkeit fertilitätserhaltender Maßnahmen informiert werden.

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Influence of high‐dose methotrexate therapy on the primordial follicles of the mouse ovary

Abstract: Our study shows that high-dose MTX causes damage to the primordial follicles of the ovaries of mice. This result may be important because young women taking high-dose MTX may suffer diminished reproductive performance and premature cessation of menses in the years following therapy.

Cited by 23 publications

References 19 publications

Effect of methotrexate and leucovorin on female reproductive tract of albino rats

Effect of methotrexate and leucovorin on female reproductive tract of albino rats

Effects of Methotrexate Therapy on the Levels of Gonadotropic Hormones in Rheumatoid Arthritis Patients of Reproductive Age

Fertilitätsprotektion bei rheumatologischen Erkrankungen

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