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Idiopathic Premature Ovarian Failure and its association to the abnormal longitudinal changes of telomere length in a population of Iranian Infertile Women: A pilot study

 

Abstract

  • Bachground

The premature ovarian failure (POF) is a reason of infertility that affects about 1–4% of women before age 40. The importance of telomeres' length in different diseases has been explored before. This study examines the association between the relative telomere length and idiopathic POF in a group of Iranian women.

  • Methods

The blood genomic DNA was extracted from 40 idiopathic POF patients (case group) and 40 fertile women (control group). The relative telomere length (RTL) was evaluated by quantitative Real-Time PCR using specific telomeric primers. RTL was calculated as T (telomere)/S (single copy gene) ratio and compared between infertile and fertile groups.

  • Results

A strong association was considered between telomere size and idiopathic premature ovarian failure. In patients the relative telomere length showed to be significantly longer than those of control group (P?

  • Conclusion

Our findings demonstrate a possible relationship between telomere lengthening and idiopathic POF. The reason of the observed elevated telomeres' genetic material could be explained by numerous probable mechanisms like reduced ovarian cell division rate, a sudden increase in the estrogen level before menopause and after egg depletion, and/or an autoimmune condition which could change the composition of blood cells and their consequent conversion to the cells with longer telomeres in patients. More experiments with larger population are necessary to confirm the results of present study.

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Immunomodulatory effects of hydroxychloroquine on Th1/Th2 balance in women with repeated implantation failure

Highlights

Elevated Th1/Th2 ratio increases cytotoxicity against embryo and leads to implantation failure.

Hydroxychloroquine significantly reduces TNF-α/IL-10 ratio.

Th1/Th2 balance is affected by hydroxychloroquine in elevated Th1/Th2 ratio.

Hydroxychloroquine shifts the responses toward Th2 and decreases the Th1/Th2 ratio.

Hydroxychloroquine can be an effective treatment for repeated implantation failure in women with immune cell abnormalities.

Abstract

  • Background

Cellular immune abnormalities such as the imbalance between T-helper (Th) 1 and Th2 cytokines have been implicated as potentially modifiable causes of idiopathic repeated implantation failures (RIF). The purpose of this study was to investigate the effects of hydroxychloroquine on IL-10 and TNF-α secretion, expression of T-bet and GATA-3 transcription factors and cellular localization of TNF-α, IFN-γ, IL-10 and IL-4 in endometrial cells in women with RIF.

  • Materials and methods

A total of 17 women with a history of RIF and elevated TNFα/IL-10 ratio (TNFα/IL-10> = 30.6) were included in the study. The serum levels of TNFα and IL-10, the expression of transcription factors related to Th1 and Th2 cells and the immune-reactivity of TNFα, IFN-γ as Th1 related cytokines and IL-10, IL-4 as Th2 related cytokines in endometrial tissues were evaluated by ELISA, real-time PCR, and fluorescent immunohistochemistry respectively. All, evaluations were done both before and after treatment with hydroxychloroquine (400 mg/orally per day).

  • Results

Hydroxychloroquine treatment significantly decreased (p < 0.0001) serum level of TNF-α and significantly increased serum level of IL-10 (p < 0.0001). T-bet, the Th1 transcription factor, expression was down-regulated and GATA-3, the Th2 transcription factor, expression was up-regulated. IL-10 and IL-4 fluorescent immunoreactivities significantly increased (p < 0.05 and p < 0.001 respectively) and TNFα and IFN-γ fluorescent immunoreactivities significantly decreased (p < 0.05) in endometrial tissue in women with RIF after treatment in comparison with before treatment.

  • Conclusion

Hydroxychloroquine administration in women with RIF With a high TNF-α/IL-10 ratio during the implantation window can decrease this ratio and seems to be an effective therapeutic strategy in RIF caused by cellular immune abnormalities through a shift in Th2 responses.

Graphical abstract

 

 

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Affiliation :

Infertility and Reproductive Health 

Research Center , Shahid Beheshti 

University of Medical Sciences, Tehran, Iran

، مرکز تحقیقات بهداشت باروری و ناباروری

، دانشگاه علوم پزشکی شهید بهشتی 

تهران، ایران

پیوندهای مهم

پایگاه اطلاع رسانی مقام معظم رهبری

پایگاه اطلاع رسانی ریاست جمهوری

پایگاه اطلاع رسانی دولت

نهاد نمایندگی مقام معظم رهبری
 
 
مرکز تحقیقات بهداشت باروری و ناباروری دانشگاه علوم پزشکی شهید بهشتی

آدرس : تهران - تجریش - میدان قدس بیمارستان            شهدای تجریش

تلفن : 22712234-021

          021-22701223

تلفکس : 22716383-021

پست الکترونیک : irhrc@sbmu.ac.ir

                           irhrc@yahoo.com

 

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