Identification and Structure Prediction of Human Septin-4 as a Biomarker for Diagnosis of Asthenozoospermic Infertile Patients—Critical Finding Toward Personalized Medicine

Abstract

Semen parameters are been found as a key factor to evaluate the count and morphology in the given semen sample. The deep knowledge of male infertility will unravel with semen parameters correlated with molecular and biochemical parameters. The current research study is to identify the motility associated protein and its structure through the in-silico approach. Semen samples were collected and initial analysis including semen parameters was analyzed by using the World Health Organization protocol. Semen biochemical parameters, namely, seminal plasma protein concentration, fructose content, and glucosidase content were calculated and evaluated for correlation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) were carried out for identification of Septin-4 presence in the semen sample. Mascot search was done for protein conformation and in-silico characterization of Septin-4 by structural modeling in Iterative Threading Assembly Refinement (I-TASSER). Twenty-five nanoseconds molecular dynamics (MD) simulations results showed the stable nature of Septin-4 in the dynamic system. Overall, our results showed the presence of motility-associated protein in normospermia and control samples and not in the case of asthenospermia and oligoasthenospermia. Molecular techniques characterized the presence of Septin-4 and as a novel biomarker for infertility diagnosis.

Biallelic loss‐of‐function mutations in SEPTIN4 ( C17ORF47 ), encoding a conserved annulus protein, cause thin midpiece spermatozoa and male infertility in humans

“…Recently, a research study tried to use an in silico approach to identify motility‐associated proteins in human semen samples. Combined with molecular techniques, they found that SEPT4 was lost in AZS samples but present in control samples (Vickram et al, 2021). Collectively, current evidence suggests that SEPT4 is a novel biomarker for diagnosing asthenoteratozoospermia.…”

The correlation of Septin4 gene expression with sperm quality, DNA damage, and oxidative stress level in infertile patients

“…Septin provides far more energy, and the ring structure provides the circulatory force that propels sperm forward in the female reproductive system rather than remaining immotile [ 6 , 13 ]. SEPTIN-4 is found in the annulus, a ring-like structure between the midpiece and the tail region of mature spermatozoa, along with other SEPTs [ 14 ]. Septin4 is required for the maintenance of normal mitochondrial architecture and the formation of the annulus during spermiogenesis [ 15 ].…”