Oligoasthenoteratozoospermic (OAT) men display altered phospholipase C ζ (PLCζ) localization and a lower percentage of sperm cells expressing PLCζ and post-acrosomal sheath WW domain-binding protein (PAWP)

Abstract

Oligoasthenoteratozoospermia (OAT) is demonstrated to be one of the most common causes of male subfertility. Phospholipase C ζ (PLCζ), a sperm-specific protein, is considered to be one of the sperm-borne oocyte activating factors (SOAFs), which play a vital role in fertilization. The post-acrosomal sheath WW domain-binding protein (PAWP) is another candidate for SOAF. The aim of this study was to compare the PLCζ localization patterns and percentage of PLCζ- and PAWP-positive sperm cells in patients with OAT and fertile men with normozoospermia. A total of 40 men included in this study were classified into two groups: OAT (n = 25) and control group (n = 15). Semen samples were collected and analyzed using conventional semen analysis according to the World Health Organization guidelines. The percentage of PLCζ- and PAWP-positive sperm cells and localization patterns of PLCζ were evaluated using immunofluorescence staining. The mean percentage of sperm cells expressing PAWP and PLCζ was significantly lower in OAT compared to control group (52.8 ± 4.2 vs. 76.8 ± 5 and 63.4 ± 3.5 vs. 86.7 ± 2.1, respectively). In addition, statistically significant differences were found with regard to the PLCζ localization patterns, including equatorial, acrosomal + equatorial, and equatorial + post-acrosomal pattern, between the two groups (p < 0.01). The present study showed a lower percentage of sperm cells expressing PLCζ and PAWP, as well as altered localization patterns of PLCζ in men with OAT. Given the role of PLCζ and PAWP in fertilization, as two major candidates for SOAFs, our findings indicate that PLCζ and PAWP impairments may be one of the possible etiologies of decreased fertility in OAT.

Antigen Unmasking Is Required to Clinically Assess Levels and Localisation Patterns of Phospholipase C Zeta in Human Sperm

“…Sperm from infertile men consistently failed to activate oocytes and could either not elicit a Ca 2+ release in mouse oocytes or did so abnormally [ 13 , 16 ]. Such sperm exhibit abrogated PLCζ [ 1 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 22 , 23 , 25 , 26 , 27 , 28 , 36 , 37 , 38 , 39 , 40 ], suggesting that PLCζ defects underlie, or at least contribute to, such cases of fertilisation failure. Clinically, complete fertilisation failure is attributed to sperm-specific defective oocyte activation, rather than any other cause [ 1 , 31 ].…”

“…Clinically, complete fertilisation failure is attributed to sperm-specific defective oocyte activation, rather than any other cause [ 1 , 31 ]. The most rapidly applicable approach is the immunocytological analysis of sperm PLCζ [ 1 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 22 , 23 , 25 , 26 , 27 , 28 , 36 , 37 , 38 , 39 , 40 ]. However, varying protocol efficiencies have yielded conflicting outcomes between studies examining human sperm PLCζ [ 15 , 18 , 29 , 32 ].…”

“…The PLCζ mutations identified from such patients were predicted to modify the enzyme fold, abrogating sperm PLCζ [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. Reduced/absent PLCζ is indicative of OAD sperm [ 1 , 13 , 16 , 18 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ], with PLCζ deficiencies increasingly associated with multiple male-specific conditions [ 1 , 16 , 18 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. Recently, using two antibodies with demonstrable specificity for PLCζ, Kashir et al [ 30 ] demonstrated that higher levels and specific localisation patterns of PLCζ in human sperm correlated to the optimal ranges of sperm fertility parameters, and higher proportions of successful fertilisation in a general population of males undergoing fertility treatment.…”

The alteration of PLCζ protein expression in unexplained infertile and asthenoteratozoospermic patients: A potential effect on sperm fertilization ability

“…Previous studies have shown that failed fertilization after ICSI in some cases of infertile men (i.e., globozoospermic, oligoasthenoteratozoospermic, normozoospermic patients) is related to reduced expression and abnormal localization of PLCζ protein (Azad et al, ; Chithiwala et al, ; Durban et al, ; Lee et al, ; Tavalaee, Nomikos, Lai, & Nasr‐Esfahani, ). Despite the key role of PLCζ in the fertilization process and its potential as biomarker for the ability of sperm to induce oocyte activation, the status of this protein in unexplained infertile (UI) and asthenoteratozoospermic (AT) men remains unclear.…”

Diagnosis and Treatment of Male Infertility-Related Fertilization Failure

“…Disruption of PLCζ by genetic mutations or reduced protein expression has been reported in patients suffering from FF after ICSI, irrespective of the sperm quality. PLCζ deficiency has been observed in normozoospermic males [39][40][41] but also in patients with abnormal sperm parameters [42,43], with globozoospermia being the most characteristic example [9,44,45]. The current evidence undoubtedly supports the role of PLCζ as a protein indispensable for successful fertilization, but there are still some unknowns that remain to be solved [46,47].…”