Bozdemir Nazlican, Biyikli Efe, Akdoganozu Utku Kagan, Uysal Fatma
Department of Histology and Embryology, Ankara Medipol University School of Medicine, Altindag, Ankara, 06050, Turkey.
Mol Biol Rep. 2025 Jun 12;52(1):587. doi: 10.1007/s11033-025-10680-3.
Infertility is a significant global reproductive health issue, impacting 9% of couples, with male factors contributing to approximately 50% of cases. Infertility in men can be caused by genetics, lifestyle, obesity, or several diseases, like oligozoospermia. In oligozoospermia, one of the most common diseases in male infertility, sperm concentration is less than 15 million/ml, and is graded as moderate, mild, and severe according to the decreasing concentration. In males,, following the onset of puberty, a complex process occurs with the contribution of many genes and proteins, resulting in the production of spermatids through mitotic and meiotic divisions from spermatogonia, a process known as spermatogenesis. The well-known p53 family, including p53, p63, and p73 transcription factors, plays an important role during spermatogenesis. It has been shown that while sperm count increased in p53 and p63 knockout mice, abnormality in sperm morphology also increased. The isoform of p73 that contains only the transactivator domain is referred to as TAp73. A significant reduction in germ cell counts and sperm maturation due to deficiencies in the spermatogenesis process was observed in TAp73 knockout mice. Furthermore, a model for oligoasthenozoospermia, characterized by low sperm count and reduced motility, was developed by inhibiting TAp73. While the roles of p53 and p63 in spermatogenesis have been thoroughly explored, the precise function of TAp73 within this context remains unclear. This review aims to shed light on the potential importance of the TAp73 transcription factor in the development of oligozoospermia.
不孕症是一个重大的全球生殖健康问题,影响着9%的夫妇,其中男性因素约占50%的病例。男性不育可能由遗传、生活方式、肥胖或几种疾病引起,如少精子症。在少精子症(男性不育中最常见的疾病之一)中,精子浓度低于1500万/ml,并根据浓度降低程度分为中度、轻度和重度。在男性中,青春期开始后,会发生一个由许多基因和蛋白质参与的复杂过程,通过精原细胞的有丝分裂和减数分裂产生精子细胞,这个过程称为精子发生。著名的p53家族包括p53、p63和p73转录因子,在精子发生过程中起重要作用。研究表明,虽然p53和p63基因敲除小鼠的精子数量增加,但精子形态异常也增加。仅包含反式激活结构域的p73同工型被称为TAp73。在TAp73基因敲除小鼠中,观察到由于精子发生过程中的缺陷,生殖细胞数量和精子成熟度显著降低。此外,通过抑制TAp73建立了一种少弱精子症模型,其特征是精子数量少和活力降低。虽然p53和p63在精子发生中的作用已得到充分研究,但在此背景下TAp73的确切功能仍不清楚。本综述旨在阐明TAp73转录因子在少精子症发生中的潜在重要性。