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Obesity-Associated Discordance Between Sperm PLCζ mRNA Expression and Protein Localization in Men: A Preliminary Evaluation

Reprod Sci. 2025 Oct 16. doi: 10.1007/s43032-025-01986-5. Online ahead of print.

ABSTRACT

Obesity is associated with low fertility potential. Ca2 + oscillations are known to be triggered after sperm oocyte membrane fusion, which allows entry of a sperm-specific phospholipase C-zeta (PLCζ), into the oocyte cytoplasm. We aimed to examine sperm PLCζ expression changes in obese and non-obese men along with sperm parameters. The demographic characteristics of the patients were analysed. The patients included in the study were divided into two groups:Non-obese patients (BMI < 30)(Control)(n:49) and the Obese Patient Group (BMI ≥ 30)n = 18). Semen analysis of the groups was evaluated. Rt-PCR analysis and histopathologic evaluation by immunohistochemistry for PLCζ expression were performed. Testosterone levels in the control group were statistically higher than in the obese group (4.8 ± 1.28 μg/L;3.6 ± 1.61 μg/L, respectively) (p < 0.05). Prolactin levels were 12.6 ± 7.2 μg/L in the control group and 17.15 ± 9.28 μg/L in the obese group, which was statistically significant (p = 0.03). No significant difference was detected between the groups in sperm concentration, motility, morphology, or viability, although semen pH was significantly higher in obese patients (p = 0.024).. Although no statistically significant was observed, PCR analysis revealed that PLCζ expression was elevated by a factor of 1.69 in obese patients. Immunohistochemical staining results showed that PLCζ expression was decreased in obese patients compared to the control group. Although PLCζ mRNA expression was higher in the obese group compared to the control group, immunohistochemical staining results demonstrated weak staining of sperm cells in the obese group. These results indicated that PLCζ protein synthesis pauses at some point in obese patients. The discrepancy between mRNA expression and protein localization may indicate translational or post-translational regulation, though this was not directly assessed in our study. This study highlights the complex relationship between obesity and male fertility, suggesting that obesity may disrupt the translation of PLCζ protein, which is crucial for successful fertilization.

PMID:41099980 | DOI:10.1007/s43032-025-01986-5

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