College of Medicine, Alfaisal University, Riyadh, Kingdom of Saudi Arabia.
School of Biosciences, Cardiff University, Cardiff, UK.
Andrology. 2020 Sep;8(5):1143-1159. doi: 10.1111/andr.12796. Epub 2020 May 20.
Oocyte activation is driven by intracellular calcium (Ca ) oscillations induced by sperm-specific PLCζ, abrogation of which causes oocyte activation deficiency in humans. Clinical PLCζ investigations have been limited to severe male infertility conditions, while PLCζ levels and localisation patterns have yet to be associated with general sperm viability.
PLCζ profiles were examined within a general population of males attending a fertility clinic (65 patients; aged 29-53), examining PLCζ throughout various fractions of sperm viability. Male recruitment criteria required a minimum sperm count of 5 × 10 spermatozoa/mL, while all female patients included in this study yielded at least five oocytes for treatment. Sperm count, motility and semen volume were recorded according to standard WHO reference guidelines and correlated with PLCζ profiles examined via immunoblotting and immunofluorescence. Appropriate fertility treatments were performed following routine clinical standard operating protocols, and fertilisation success determined by successful observation of second polar body extrusion.
Four distinct PLCζ patterns were observed at the equatorial, acrosomal + equatorial regions of the sperm head, alongside a dispersed pattern, and a population of spermatozoa without any PLCζ. Acrosomal + equatorial PLCζ correlated most to sperm health, while dispersed PLCζ correlated to decreased sperm viability. Total levels of PLCζ exhibited significant correlations with sperm parameters. PLCζ variance corresponded to reduced sperm health, potentially underlying cases of male sub-fertility and increasing male age. Finally, significantly higher levels of PLCζ were exhibited by cases of fertilisation success, alongside higher proportions of Ac + Eq, and lower levels of dispersed PLCζ.
PLCζ potentially represents a biomarker of sperm health, and fertilisation capacity in general cases of patients seeking fertility treatment, and not just cases of repeated fertilisation. Further focused investigations are required with larger cohorts to examine the full clinical potential of PLCζ.
卵母细胞的激活是由精子特异性 PLCζ 诱导的细胞内钙离子(Ca2+)振荡驱动的,其缺失会导致人类卵母细胞激活不足。临床 PLCζ 的研究仅限于严重的男性不育症,而 PLCζ 的水平和定位模式尚未与精子的普遍活力相关联。
在一家生育诊所就诊的男性一般人群中(65 例患者;年龄 29-53 岁)检查了 PLCζ ,研究了 PLCζ 在不同精子活力分数中的分布情况。男性招募标准要求精子计数至少为 5×106 个/毫升,而本研究中包括的所有女性患者均至少产生了 5 个卵母细胞进行治疗。精子计数、活力和精液量根据世界卫生组织(WHO)的参考标准进行记录,并与通过免疫印迹和免疫荧光检查的 PLCζ 图谱相关联。根据常规临床标准操作方案进行适当的生育治疗,并通过观察第二极体的成功排出来确定受精成功。
在精子头部的赤道区、顶体+赤道区以及弥散区观察到四种不同的 PLCζ 模式,还有一群没有任何 PLCζ 的精子。顶体+赤道 PLCζ 与精子健康相关性最大,而弥散 PLCζ 与精子活力降低相关性最大。PLCζ 的总水平与精子参数显著相关。PLCζ 的方差与精子健康状况下降相对应,可能是男性亚生育能力和年龄增加的潜在原因。最后,在受精成功的病例中,PLCζ 的水平显著升高,同时 Ac+Eq 的比例升高,而弥散 PLCζ 的水平降低。
PLCζ 可能代表了寻求生育治疗的患者的精子健康和受精能力的生物标志物,而不仅仅是反复受精的病例。需要进一步进行有更大样本量的重点研究,以检验 PLCζ 的全部临床潜力。