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High Salt Diet Impairs Male Fertility in Mice via Modulating the Skeletal Homeostasis

  • Reproductive Biology: Original Article
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Abstract

Male reproductive functions and bone health are both adversely affected by the high salt diet (HSD). Nevertheless, the underlying mechanism via which it alters the sperm function remains largely unknown. This study examines the mechanism by which HSD affects male fertility by impairing bone health. For investigating the same, male BALB/c mice were categorized into three groups—HSD group (fed with 4% NaCl), a low salt diet (LSD) group (fed with 0.4% NaCl), and a control group (fed with a normal diet) for 6 weeks and thereafter assessed for various sperm parameters, bone turnover markers, and testosterone levels. Furthermore, the quantitative assessment of testosterone biosynthesis enzymes was performed. Interestingly, we observed that mice fed with HSD showed significant alterations in sperm parameters—motility, count, and vitality, including morphological changes compared to both the LSD and the control groups. In addition, serum analysis showed an increase in bone resorption markers and a decrease in bone formation markers in the HSD group (p < 0.05). Further, HSD caused a decrease in the testosterone level and mRNA expression of testosterone biosynthesis enzymes. Importantly, a significant decrease in bone formation marker osteocalcin (OC) was observed to coincide with the dip in testosterone level in the HSD group. Given that OC plays a key role in maintaining male fertility, the above findings suggest that a decrease in OC levels may affect the testosterone biosynthesis pathway, reducing testosterone hormone secretion and thereby resulting in decreased spermatogenesis. The study for the first time delineates and bridges the mechanism of HSD-mediated bone loss (results in a deficiency of OC) with decreased testosterone biosynthesis and thus impaired male fertility.

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Data Availability

The data and material that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors wish to thank Dr. Sushil Saini at National Dairy Research Institute for assistance in RNA isolation and qPCR, Dr. Kriti for ELISA analysis, and Miss Kajal Sihag for sperm microscopy.

Funding

This study was supported by the AIIMS intramural project A-619 sanctioned to Dr. Shrabani Saugandhika.

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  1. Department of Biotechnology, All India Institute of Medical Sciences, New Delhi, 110029, India

    Shrabani Saugandhika, Leena Sapra, Kiran Kumari & Rupesh K. Srivastava

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Correspondence to Shrabani Saugandhika or Rupesh K. Srivastava.

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The study protocol was reviewed and approved by the Animal Ethics Committee of All Institute of Medical Sciences, New Delhi, India (Approval number- 64/1AEC-1/2018).

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Supplementary Materials

Fig 1 Correlation analysis of Testosterone with OC and other bone turnover markers: (Pearson correlation) a) OC, Testosterone correlation; *p < 0.05, r2=0.972 b) OPG, Testosterone correlation; *p < 0.05, r2=0.97 c) CTX-II, Testosterone correlation; *p < 0.05, r2=0.904, d) RANKL, Testosterone correlation; *p < 0.05, r2=0.905, e) ALP, Testosterone correlation; *p < 0.05, r2=0.974. (DOCX 90 kb)

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Saugandhika, S., Sapra, L., Kumari, K. et al. High Salt Diet Impairs Male Fertility in Mice via Modulating the Skeletal Homeostasis. Reprod. Sci. 30, 3339–3352 (2023). https://doi.org/10.1007/s43032-023-01278-w

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