Function of manchette and intra-manchette transport in spermatogenesis and male fertility
Tingting Gao, Yang Liu, Jinghong Li, Y N Zhang, Bin Wu
Abstract
The manchette is a transient skirt-like structure consisting of microtubules (MTs) and filamentous actin (F-actin) surrounding the elongating sperm head during spermiogenesis. It is pivotal in sperm head shaping controlled by the acrosome-acroplaxome-manchette complex, acrosome formation, and flagellar assembly by microtubular-based protein delivery. Defects in the manchette frequently lead to teratozoospermia concomitant with oligozoospermia and asthenozoospermia, but the pathogenic mechanism underlying manchette function and its role in male infertility remain poorly understood. In this review, we systematically described the assembly and disassembly of the manchette, intra-manchette transport (IMT) and its regulatory model, the function and mechanism of manchette and IMT in regulating sperm head shaping and flagellar assembly during spermatogenesis; summarized the research progress of manchette-related genes related to male infertility; and listed the manchette-related proteins in knockout mouse models and clinical cases, which provide the theoretical basis for an in-depth understanding of the molecular mechanism of manchette involved in spermatogenesis and male fertility for understanding the potentially developing treatments for infertility and reproductive disorders. The manchette regulates sperm head formation by mediating LINC complex-dependent transport during nuclear condensation, facilitating assembly of the AAM structure to stabilize the sperm head skeleton, and driving zipper-like movement to compress and maintain the nucleus after chromatin condensation. The manchette primarily regulates the assembly of flagellar accessory structures by exerting its storage and transportation functions. Intra-manchette transport (IMT) facilitates protein and vesicle transport, essential for nuclear condensation and sperm tail assembly, with defects leading to male infertility. Key proteins like KIF3A, HOOK1, and SPAG6 are involved in manchette function, with mutations causing abnormal sperm morphology and infertility. Mutations in manchette-related genes (e.g., CFAP43, CFAP65) are linked to severe asthenozoospermia and multiple morphological abnormalities of the sperm flagellum (MMAF).