Intracytoplasmic injection of spermatozoa and spermatogenic cells: its biology and applications in humans and animals

Abstract

Intracytoplasmic sperm injection (ICSI) has become the method of choice to overcome male infertility when all other forms of assisted fertilization have failed. Animals in which ICSI has produced normal offspring include many species. Success rate with normal spermatozoa is well above 50% in the mouse but ICSI success rates in other animals have been low, ranging from 0.3 to 16.5%. Mouse ICSI revealed that spermatozoa that cannot participate in normal fertilization can produce normal offspring by ICSI, provided their nuclei are genomically intact. Human ICSI using infertile spermatozoa has been highly successful perhaps because of the intrinsic instability of human sperm plasma membrane. The health of children born after ICSI and other assisted fertilization techniques is of major concern. Careful analyses suggest that higher incidences of congenital malformations and/or low birth weights after assisted fertilization are largely attributable to parental genetic background and increased incidence of multiple births, rather than to the techniques of assisted fertilization. Since the physiological and nutritional environments of developing embryos may cause persisting alteration in DNA methylation, extreme caution must be exercised in handling gametes and embryos in vitro. In the mouse, round spermatid injection (ROSI) has been routinely successful but its use in humans is controversial. Whether human ROSI and assisted fertilization involving younger spermatogenic cells are medically safe must be the subject of further investigations.

Incorporation of the acrosome into the oocyte during intracytoplasmic sperm injection could be potentially hazardous to embryo development

“…Removal of acrosomes is a key to success of hamster ICSI. Although ICSI has been successful for many other species (24), no systematic study has been conducted to determine whether the presence or absence of the acrosomes in spermatozoa affects the outcome of ICSI. Here, we report that mouse oocytes became deformed and cytolyzed when three or more acrosome-intact mouse spermatozoa were injected into each oocyte.…”

“…Fortune has smiled on human and mouse ICSI because the acrosomes of these species happen to be rather small (24). If human sperm acrosomes were as large as hamster or bull sperm acrosomes and if human oocytes (Ϸ7 ϫ 10 5 m 3 ) were as small as mouse oocytes (Ϸ2.7 ϫ 10 5 m 3 ), human ICSI could have been problematic from its inception.…”

“…The efficiency of ICSI (the proportion of live offspring developed from all ICSI oocytes) in species other than humans and mice is rather low: Ϸ15% at best (24). The removal of acrosomes before ICSI may increase its efficiency.…”

Kinetics of human male pronuclear development in a heterologous ICSI model

“…It has been suggested that they may interfere with sperm chromatin remodeling [19][20][21][22]. Regardless, live offspring have been born using ICSI in a variety of species, including humans and mice [23]. However, existing reports on higher incidence of chromosome aberrations [24] and lower developmental potentials [25,26] in embryos produced by ICSI indicate that further evaluations on the effects of the incorporation of the acrosome into the oocyte are needed.…”

Better intracytoplasmic sperm injection without sperm membranes and acrosome

“…M illions of years of evolution leading to a well orchestrated series of events for sperm transport and selection in the female tract and sperm-egg interaction during fertilization can be bypassed by the direct microinjection of spermatozoa into oocytes to alleviate infertility or for the experimental manipulation of model animals (1). Since its introduction in humans (2), many thousands of children have been born by using intracytoplasmic sperm injection (ICSI).…”