1022-7954/03/3907- $25.00 © 2003
Russian Journal of Genetics, Vol. 39, No. 7, 2003, pp. 811–815. Translated from Genetika, Vol. 39, No. 7, 2003, pp. 969–974.
Original Russian Text Copyright © 2003 by Daev, Dukelskaya.
Effects of various stress factors on genetic processes in
animal target cells were originally studied by M.E. Loba-
shev, Yu.Ya. Kerkis, and D.K. Belyaev (reviewed in ).
There are two main aspects to this problem: the inﬂuence
of stress reaction on the expression of preexisting genetic
variation and the ability of various stressors to initiate
recombination and mutations de novo [2–5].
Volatile compounds released into the air by mice
and other rodents may, in some situations, act as potent
stress factors drastically destabilizing the hormonal
balance in recipient animals . Therefore, these com-
pounds (pheromones) may serve as model stress factors
in studies of the effect of pheromonal stress on various
genetic processes. For example, mouse and rat phero-
mones have been demonstrated to modify the activity
of early response genes in cells of some speciﬁc zones
of olfactory epithelium in male and female recipients
[7–9]. In mice, they increase the rate of cytogenetic
alterations during mitotic and meiotic divisions [4, 10],
which changes the frequency of dominant lethals in the
offspring of males subjected to stress. Thus, phero-
mones affect the regulation of reproduction in mice.
The test for the induction of abnormal sperm heads
(ASHs) or sperm-head test is one of the tools used to
study the effects of mutagenic factors on reproduction
in mammals. This test is widely used for studying the
effects of genotoxic agents on germ cells in humans and
nonhuman animals [11, 12]. It is also used to study the
mechanisms of decreased fertility and infertility [13, 14].
The sperm-head test in inbred laboratory strains of
mice is a well-developed model for various studies on
reproduction control [15, 16]. Earlier, it was shown that
a complex mixture of unidentiﬁed volatile components
of the urine of mature males affected ASH frequency in
young males .
We studied the effect of 2,5-dimethylpyrazine
(2,5-DMP), a pheromone released by female mice kept
at a high population density , on ASH frequency in
mature CBA males. Earlier, several researchers demon-
strated that female pheromones stimulate male repro-
ductive function in mice . However, the ﬁnding and
identiﬁcation of the volatile component that female
rodents release only if kept in overcrowded cages and
that is detrimental for other individuals irrespective of
their sex  provides a concrete example of an adap-
tive response of chemocommunication mechanisms to
changing zoosocial conditions. The genetic compo-
nents of these mechanisms have been studied poorly,
which motivated us to perform this study.
MATERIALS AND METHODS
Three- to four-month-old highly inbred CBA males
1 g were obtained from the Rappolovo
laboratory animal care center of the Russian Academy
of Medical Sciences. All mice were kept singly in stan-
dard polypropylene cages (22
10 cm) in the
vivarium of the Laboratory of Animal Genetics of Bio-
logical Research Institute of St. Petersburg State Uni-
versity. Sawdust was used as a litter. The illumination
(a noninverted day with a photoperiod of 12 h) and ven-
tilation regimens were maintained automatically. The
food and feeding conditions were identical.
After a two-week adaptation, part of CBA males
were subjected to pheromonal stressor in a separate
room. For this purpose, a perforated capsule containing
The Female Pheromone 2,5-Dimethylpyrazine
Induces Sperm-Head Abnormalities in Male CBA Mice
E. V. Daev and A. V. Dukelskaya
Department of Genetics and Breeding, St. Petersburg State University, St. Petersburg, 199034 Russia;
fax: (812)328-05-41; e-mail: email@example.com
Received December 4, 2002
—The effect of the house mouse female pheromone 2,5-dimethylpyrazine (2,5-DMP) on sperm dif-
ferentiation in male CBA mice has been studied. For this purpose, mature males were treated with a 0.01%
aqueous solution of the pheromone for six days. Control mice were similarly treated with physiologic saline.
The mice were sacriﬁced 23 days after the treatment, and material for the analysis of sperm-head abnormalities
was sampled from the caudal portion of the epididymis. Analysis of the frequency of abnormal sperms has dem-
onstrated that the pheromonal treatment signiﬁcantly increases the frequencies of various sperm-head abnor-
malities. Apparently, this results from disturbances in germ cell differentiation caused by the induction of
genetic damage at stages immediately preceding meiosis, as well as during the ﬁrst and second meiotic divi-
sions. The relationship between the effect of 2,5-DMP and the decrease in the fertility of male CBA mice that
was earlier observed after a similar treatment is discussed.