Male infertility caused by spermiogenic defects: lessons from gene knockouts

Abstract

Spermiogenesis refers to the process by which postmeiotic spermatids differentiate into elongated spermatids and eventually spermatozoa. During spermiogenesis, round spermatids undergo dynamic morphologic changes, which include nuclear condensation and elongation, formation of flagella and acrosome, reorganization of organelles and elimination of cytoplasm upon spermiation. This cellular differentiation process is unique to male haploid germ cells, which may explain why approximately half of the testis-specific genes are exclusively expressed in spermiogenesis. The spermiogenesis-specific expression implies that these genes contribute to either structural or functional aspects of future sperm. Many such genes have been inactivated in mice and some of these gene knockout mice display male infertility due to nonfunctional sperm which display no or various degrees of structural abnormalities. Since the majority of these spermiogenesis-specific genes are highly conserved between mice and humans, findings from knockout mouse studies may be applicable to human infertility. Here, I briefly review some of these spermatid-specific gene knockouts. The mouse studies strongly suggest that sperm quality rather than quantity is a better indicator of male fertility and novel assays should be developed to determine sperm functionality.

Fig. 1

Genes essential for each of the multiple steps of spermiogenesis, as revealed by gene knockout studies in mice. Mouse spermiogenesis consists of 16 steps (labeled with 1–16) and specific associations between stages of the seminiferous epithelial cycle (marked with Roman numerals I–XII) and developing steps of spermatids are shown.

Fig. 2

Ultrastructure of the mouse epididymal sperm. (A) Scanning electron microscopic image of a mouse epididymal sperm. (B) Transmission electron microscopic (TEM) image of the longitudinal section of the head and neck regions of a sperm. (C) TEM image of a cross-section from the mid-piece of the sperm tail. (D) TEM image of a cross-section from the junction between the mid-piece and principal piece of the sperm tail where the cytoplasmic droplet is located. (E and F) TEM images of cross-sections from middle and lower portions of the principal piece of the sperm tail, respectively. (G) TEM image of a cross-section from the end piece of the sperm tail.