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Cervical fluid pH, electrolytes and osmolarity changes and expression of ion transporters (ENaC, CFTR and AQP) in cervix of women with primary unexplained infertility

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Abstract

Background

Unexplained infertility could arise from a defect in the cervix. However, the contribution of abnormal cervical fluid microenvironment to this problem still needs to be identified. Therefore, this study identifies the changes in the cervical fluid microenvironment, i.e., pH, electrolytes and osmolarity as well as expression of ion transporters in the cervix including ENaC, CFTR and AQP in fertile women and in women suffering from primary unexplained infertility.

Methods

Fertile women and women with unexplained infertility but having regular 28-day menstrual cycles were chosen in this study, Day-22 serum progesterone levels were determined. In the meantime, serum FSH and LH levels were determined on day 2 while, cervical flushing was performed at day 14 to analyse changes in the cervical fluid pH, osmolarity, Na+ and Cl− levels. Meanwhile, cells retrieved from cervical fluid were subjected to mRNA expression and protein distribution analysis for CFTR, AQP and ENaC by qPCR and immunofluorescence, respectively.

Results

No significant changes in serum progesterone, FSH and LH levels were observed between the two groups. However, cervical fluid pH, osmolarity, Na+ and Cl− levels were significantly lower in primary unexplained infertile group when compared to fertile group. Expression of CFTR and AQP (AQP 1, AQP 2, AQP 5 and AQP 7) in endocervical cells was lower and expression of β-ENaC was higher in primary unexplained infertile women (p < 0.05 when compared to fertile group).

Conclusions

Alterations in the cervical fluid microenvironment linked to the defective ion transporter expression in the cervix might contribute towards the unfavourable condition that accounts for unexplained infertility in women.

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Funding

This work is supported by a PPP grant, PG304-2016 A, University of Malaya, Kuala Lumpur, Malaysia.

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Authors and Affiliations

  1. Department of Physiology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, 50603, Malaysia

    Nurain Ismail, Kyaimon Myint, Nelli Giribabu & Naguib Salleh

  2. Department of Obstetrics & Gynaecology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, 50603, Malaysia

    Si Lay Khaing

  3. Medical Education Department, University of Medicine, Yangon, Myanmar

    Si Lay Khaing

Authors
  1. Nurain Ismail
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  2. Kyaimon Myint
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  3. Si Lay Khaing
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Contributions

NI: Formal analysis, Data curation, Investigation, Software, Validation, Writing – original draft and KY: Investigation, Methodology, Writing – review & editing. SLK: Investigation, Data curation, Formal analysis, and NG: Investigation, Data curation, Formal analysis, Methodology, and NS: Conceptualization, Funding acquisition, Project administration, Supervision Conceptualization, Methodology, Writing – review & editing.

Corresponding author

Correspondence to Naguib Salleh.

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The authors have no relevant financial or non-financial interests to disclose.

Ethics approval

This study involved humans and ethics approved by the University of Malaya Medical Centre, with ethics number 201410-676.

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Written informed consent was obtained from the parents.

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Ismail, N., Myint, K., Khaing, S.L. et al. Cervical fluid pH, electrolytes and osmolarity changes and expression of ion transporters (ENaC, CFTR and AQP) in cervix of women with primary unexplained infertility. Mol Biol Rep 50, 6729–6737 (2023). https://doi.org/10.1007/s11033-023-08555-6

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