Premature ovarian insufficiency – hormone replacement therapy and management of long-term consequences

Machura, Paulina; Grymowicz, Monika; Rudnicka, Ewa; Piȩta, Wojciech; Calik-Ksepka, Anna; Skórska, Jolanta; Smolarczyk, Roman

doi:10.5114/pm.2018.78559

“…POI is one of the causes of infertility, and the great challenge is that it is difficult to cure or reverse. In addition, patients with POI can often exhibit serious mental and physical problems [35,36]. And it was confirmed that imatinib could provide selective protection against CDDP induced ovarian injury [37].…”

Section: Discussionmentioning

confidence: 86%

Elevated levels of miR-483-5p in oocytes aggravates premature ovarian insufficiency induced by CDDP by targeting the FKBP4

Zhao

¹

,

Gu

²

,

Ouyang³

et al. 2020

Preprint

1

0

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Background: Premature ovarian insufficiency (POI) is characterized by a loss of ovarian function before 40 years-of-age and represents an existing challenge cause of female infertility. POI is one of the dominant causes of cis-diaminedichloroplatinum (cisplatin, CDDP)-induced reproductive impairment. However, the detailed mechanisms underlying POI induced by CDDP remain unclear.Methods: The POI C57B6/J mouse model was created by administering CDDP. The effects of FKBP4 were investigated using isobaric tags for relative and absolute quantification analysis (iTRAQ), real-time quantitative PCR (qRT-PCR) and western blotting. Target prediction was predicted using TargetScan software. Levels of sex hormones were tested using Enzyme-linked immunosorbent assays (ELISA).Results: We found that the FKBP4 protein was down-regulated in the ovaries of CDDP model. Target prediction identified FKBP4 as a potential target for miR-483-5p, which was expressed at high levels in both the ovaries and serum of CDDP-POI mice, and in the serum from POI patients. In vitro experiments further confirmed that FKBP4 was the target for miR-483-5p in human cervical cancer cells (HeLa). The overexpression of FKBP4 in human granulosa cells (KGN) alleviated the apoptosis caused by CDDP and the overexpression of miR-483-5p. Furthermore, the overexpression of miR-483-5p in oocytes caused injury to the ovaries, and disrupted the levels of sex hormones in CDDP-POI mice (AMH: P < 0.01; E2: P < 0.01; FSH: P < 0.01).Conclusions: Analyses showed that miR-483-5p targets the FKBP4 protein in a mouse model of POI induced by CDDP. Elevated levels of miR-483-5p in oocytes could aggravate POI induced by CDDP by targeting FKBP4. Overall, our data demonstrate that miR-483-5p was responsible for the underlying pathophysiology of POI induced by chemotherapeutic treatments, such as CDDP.

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“…POI is one of the causes of infertility, and the great challenge is that it is di cult to cure or reverse. In addition, patients with POI can often exhibit serious mental and physical problems [35,36]. One of the major causes is that chemotherapy drugs were applied to the treatment of childhood cancer.…”

Section: Discussionmentioning

confidence: 99%

Elevated levels of miR-483-5p in oocytes aggravates premature ovarian insufficiency induced by CDDP by targeting the FKBP4

Zhao

¹

,

Gu

²

,

Ouyang³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Premature ovarian insufficiency (POI) is characterized by a loss of ovarian function before 40 years-of-age and represents an existing challenge cause of female infertility. POI is one of the dominant causes of cis-diaminedichloroplatinum (cisplatin, CDDP)-induced reproductive impairment. However, the detailed mechanisms underlying POI induced by CDDP remain unclear.Methods: The POI C57B6/J mouse model was created by administering CDDP. The effects of FKBP4 were investigated using isobaric tags for relative and absolute quantification analysis (iTRAQ), real-time quantitative PCR (qRT-PCR) and western blotting. Target prediction was predicted using TargetScan software. Levels of sex hormones were tested using Enzyme-linked immunosorbent assays (ELISA).Results: We found that the FKBP4 protein was down-regulated in the ovaries of CDDP model. Target prediction identified FKBP4 as a potential target for miR-483-5p, which was expressed at high levels in both the ovaries and serum of CDDP-POI mice, and in the serum from POI patients. In vitro experiments further confirmed that FKBP4 was the target for miR-483-5p in human cervical cancer cells (HeLa). The overexpression of FKBP4 in human granulosa cells (KGN) alleviated the apoptosis caused by CDDP and the overexpression of miR-483-5p. Furthermore, the overexpression of miR-483-5p in oocytes caused injury to the ovaries, and disrupted the levels of sex hormones in CDDP-POI mice (AMH: P < 0.01; E2: P < 0.01; FSH: P < 0.01).Conclusions: Analyses showed that miR-483-5p targets the FKBP4 protein in a mouse model of POI induced by CDDP. Elevated levels of miR-483-5p in oocytes could aggravate POI induced by CDDP by targeting FKBP4. Overall, our data demonstrate that miR-483-5p was responsible for the underlying pathophysiology of POI induced by chemotherapeutic treatments, such as CDDP.

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“…In addition, patients with POI can often exhibit serious mental and physical problems. [29,30] Consequently, there is an urgent need to identify preventive diagnostic markers and effective treatments for POI patients. There is a growing body of evidence to suggest that microRNAs (miRNAs) are important regulators in the pathogenesis of POI.…”

Section: Discussionmentioning

confidence: 99%

Elevated levels of miR-483-5p in oocytes aggravates premature ovarian insufficiency induced by CDDP by targeting the FKBP4

Zhao¹,

Gu²,

Ouyang³

et al. 2020

Preprint

0

View full text Add to dashboard Cite

Background Premature ovarian insufficiency (POI) is characterized by a loss of ovarian function before 40 years-of-age and represents a major cause of female infertility. POI is one of the dominant causes of cis-diaminedichloroplatinum (cisplatin, CDDP)-induced reproductive impairment. However, the detailed mechanisms underlying POI induced by CDDP remain unclear. Methods The POI C57B6/J mouse model was created by administering CDDP. The effects of FKBP4 were investigated using isobaric tags for relative and absolute quantification analysis (iTRAQ), real-time quantitative PCR (qRT-PCR) and western blotting. Target prediction was predicted using TargetScan software. Levels of sex hormones were tested using Enzyme-linked immunosorbent assays (ELISA). Results We found that the FKBP4 protein was down-regulated in the ovaries of CDDP model. Target prediction identified FKBP4 as a potential target for miR-483-5p , which was expressed at high levels in both the ovaries and serum of CDDP-POI mice, and in the serum from POI patients. In vitro experiments further confirmed that FKBP4 was the target for miR-483-5p in human cervical cancer cells (HeLa). The overexpression of FKBP4 in human granulosa cells (KGN) alleviated the apoptosis caused by CDDP and the overexpression of miR-483-5p . Furthermore, the overexpression of miR-483-5p in oocytes caused injury to the ovaries, and disrupted the levels of sex hormones in CDDP-POI mice (AMH: P <0.01; E 2 : P <0.01; FSH: P <0.01). Conclusions Analyses showed that miR-483-5p targets the FKBP4 protein in a mouse model of POI induced by CDDP. Elevated levels of miR-483-5p in oocytes aggravated POI induced by CDDP by targeting FKBP4. Overall, our data demonstrate that miR-483-5p was responsible for the underlying pathophysiology of POI induced by chemotherapeutic treatments, such as CDDP.

show abstract

Premature ovarian insufficiency – hormone replacement therapy and management of long-term consequences

Cited by 27 publications

References 26 publications

Elevated levels of miR-483-5p in oocytes aggravates premature ovarian insufficiency induced by CDDP by targeting the FKBP4

Elevated levels of miR-483-5p in oocytes aggravates premature ovarian insufficiency induced by CDDP by targeting the FKBP4

Elevated levels of miR-483-5p in oocytes aggravates premature ovarian insufficiency induced by CDDP by targeting the FKBP4

Elevated levels of miR-483-5p in oocytes aggravates premature ovarian insufficiency induced by CDDP by targeting the FKBP4

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