NATURE OF THE SYSTEMIC EFFECT OF LITTER SIZE

ON GESTATION PERIOD IN MICE

ANNE McLAREN and DONALD MICHIE

Agricultural Research Council Unit of Animal Genetics, Institute of Animal Genetics,

Edinburgh 9, and Department of Surgical Science, University of Edinburgh
(Received 9th January 1963)
Summary. In two situations where it was possible to vary total foetal
mass independently of foetal number, the heavier young were associated
with a shorter gestation period. We therefore conclude that the systemic
effect of number in the litter on gestation period in mice reflects the total
mass of foetal or placental tissue, and that the number of implants is only

indirectly relevant.
An inverse relationship between litter size and gestation period is commonly
found in mammals including man. In the preceding paper Biggers, Curnow,
Finn & McLaren (1963) have described an experimental analysis of this
phenomenon in the mouse. They show that the controlling influence emanates
from the foetuses themselves or associated placental tissue, and not from the
corpora lutea formed in the ovary following ovulation. They also show that
the litter-size effect operates systemically rather than locally: it is unaffected
by the distribution of implanted foetuses between the two uterine horns, and
hence is not an expression of intra-uterine crowding in any simple sense.
We are thus left with two clearly defined alternatives. Control over gestation
period is exerted either ( 1 ) by the total number of implants, irrespective of the
quantity of foetal or placental tissue involved, or (2) by the total quantity of
foetal or placental tissue, irrespective of the number of implants contributing
to this quantity.
Experimental discrimination between the two possibilities requires a means
of varying one of these two highly correlated variables independently of the
other. In the work which we shall describe, we tested in mice the effects of two
conditions known to increase the total foetal (and possibly placental) mass for
a given implant number. First, the gestation periods of inbred litters were

compared with those of Fi hybrid litters from females of the same strain. The
strain combination was one in which Fi hybrid young were heavier than inbred
young at birth. Secondly, accelerated prenatal development was achieved by
experimentally transplanting 'precocious' 3|-day embryos into pregnant
females taken 2| days post coitum. In such a situation, Noyes, Gates & Bentley
(1961) and Noyes, Doyle & Bentley (1961) have shown that all the embryos
implant at the same time, but that the precocious ones show a higher growth
rate after implantation. Both variants formed part of an experiment designed
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140 Anne McLaren and Donald Michie

primarily to investigate a maternal effect (see McLaren & Michie, 1958, for
further experimental details).
Text-fig. 1 shows that females of the C57BL inbred strain pregnant with
(C3H x C57BL) Fi foetuses delivered their young nearly half a day earlier on
average than when pregnant with the same number of C57BL inbred young.
The difference is significant at the 1 % probability level. The duration of

.2 19

ili 16
U 6
No. young born
Text-fig. 1.Regression of gestation period on number of young born in 114 inbred
(C57BL female C57BL male) and seventy-nine Fi hybrid (C57BL female x C3H male)
litters.
•-· =
Inbred; - =Fi hybrid.
20

5 7 11
No. young born

Text-fig. 2. Regression of gestation period on number of young born for litters born to
C57BL mothers, which contained at least one young developed from a precocious
transferred embryo. The calculated regression line for control C57BL litters has been
drawn in from Text-fig. 1.
• = Mean values for twelve litters containing at least one inbred (C3H) transferred
embryo.
= Mean values for twenty-six litters containing at least one Fi hybrid (C3H x C57BL)
transferred embryo.

pregnancy was taken as the interval between the finding of a vaginal plug in
the female, and the birth of the litter.
In Text-fig. 2 the calculated regression line for inbred litters is given together
with the mean gestation period values for 'mixed' litters from the egg-transfer
variant of the investigation. Each mixed litter contained a variable number of
young derived from precocious transferred embryos, either Fi hybrid (C3H
C57BL) or inbred (C3H), and in addition a variable number of native C57BL

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 Effect of litter size on gestation period 141
embryos, not precocious, derived from the mother's own mating. Gestation
period is plotted against the total number of young in the fitter, and it will be
seen that the points representing mean values for the mixed litters lie always
below the inbred regression line. In other words the presence of precocious
embryos, whether inbred or Fi, shortens the gestation period.
Both lines of evidence thus support the second of the two alternatives listed
earlier. They do not, however, help to decide whether it is the total amount of
foetal or of placental tissue which is causally involved.

REFERENCES
Biggers, J. D., Curnow, R. N., Finn, C. A. & McLaren, A. (1963) Regulation of the gestation
period in mice. J. Reprod. Fértil. 6, 125.
McLaren, A. & Michie, D. (1958) Factors affecting vertebral variation in mice. 4. Experimental
proof of the uterine basis of a maternal effect. J. Embryol. exp. Morph. 6, 645.
Noyes, R. W., Doyle, L. L. & Bentley, D. L. (1961) Effect of preimplantation development on foetal
weight in the rat. J. Reprod. Fértil. 2, 238.
Noyes, R. W., Gates, . . & Bentley, D. L. (1961) Ovular maturation and fetal development.
Fértil. Steril. 12, 405.

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