What Is The Breeding Process?

In Simple Terms... • In More Detailed Terms...

First, you need a male and a female mouse. Put the female in the male’s cage or the female will fight to protect her territory from the ‘invading’ male. Female mice come into heat every five days or so, so you should leave the male in the cage with the female for around 10 days to ensure pregnancy. Then remove the male and place him in a separate cage. You can construct a nesting box for the female if you want to - it doesn't have to be anything fancy, a cardboard box will do. Take out her wheel for the safety of the babies.

Mum mouse (Eve) sitting on her nest of pinkies, cleaning a self black pup. Mother mice lick the stomachs and genitals of their babies after they have been fed to stimulate them to go to the toilet; without this stimulation they will not defecate or urinate and this will soon become fatal.

Switch her diet to something high fat (add more sunflower seeds, puppy/kitten kibble, eggflake, nuts and grains to her normal diet), or give her home-made fatty foods like hard-boiled egg yolks, peanut butter and cooked beans. Don't give her dairy products unless they are specially meant for pets (i.e. lactose free). The female will have her babies in about three weeks, tending on the longer end of three weeks. She will have anywhere from one to 32 babies.

If you can, find out more about her family. If her mother had litters of 15 to 20 your girl will probably have large litters too. If her mother had litters of two to six your girl will probably have small litters. Mice have eight to 12 nipples and litters larger than that usually fail to thrive. However, if you have a good mothering female everything will be fine, but you should definitely give her a break from breeding for at least three weeks (preferably two months or more) and some nice fatty foods while she is nursing. If the male is still in with her after she gives birth she will immediately go into heat and will be impregnated again within a few hours. It is advisable not to do this as it puts strain on the mother and both litters.

Necessary Facts
Heat cycle of female: every 3 - 5 days
Gestation period: average 21 days
Litter size: 8 -12 average

Four pinkies born to a black banded mum

In More Detailed Terms ...

The Oestrus Cycle
The normal oestrus cycle of a mouse is 4-6 days in length. The cycle has been divided into four phases which are distinguished by changes in physiology, morphology, and behaviour.

(1) The proestrus portion of the cycle begins when a new batch of eggs reach maturity within ovarian follicles that are ripe and large. External examination of the female will usually show a bloated vulva with an open vagina.

(2) Oestrus begins with the ovulation of fully mature oocytes. The vulva remains in an extended state with an open vagina, and females are maximally receptive to male advances. When mice are maintained on a standard light-dark cycle, the oestrus phase will usually begin soon after midnight and last for 6-8 hours.

(3) The metestrus phase follows, when mature eggs move through the oviducts and into the uterus. The vulva is no longer bloated, and the vagina is now closed.
At the end of metestrus, a physiological branch point occurs with the direction to be taken dependent on whether a successful copulation has occurred. The act of successful copulation induces hormonal changes that prepare the uterus for a pregnancy which will ensue under normal circumstances. However, a sterile copulation - one that does not lead to fertilization - can induce a state of pseudopregnancy. A pseudopregnancy can extend the metestrus phase by as long as 10-13 days.

(4) If pregnancy does not occur, the metestrus phase is ultimately followed by the last phase of the oestrus cycle, diestrus. Unfertilised eggs are eliminated, the vagina and vulva are at a minimum size, and new follicles begin to undergo a rapid growth for the next ovulation. (The proestrus and oestrus phases together constitute the follicular phase; the metestrus and diestrus phases together constitute the luteal phase.)

Mating
Once animals have been together for more than a few days, mating will be restricted to the late proestrus/early oestrus portion of the female cycle. It is only during this period that a female will be receptive and that a male will normally be interested. (However, in some instances, when a new couple is first brought together in a cage, the male will rape his partner, irrespective of her oestrus phase). Mating typically occurs over a period of 15-60 minutes with clear strain-specific differences: DBA males are quick (20 minutes) and BALB/c males are slow (one hour) according to Wimer and Fuller (1966). The male first examines the female genitalia and then mounts his mate and withdraws from one to one hundred times until ejaculation occurs during a final mounting. The male is quiet for a short period of time and then resumes normal activity. Although a full sperm count is not built up again for two days, it is possible for a male, especially an outbred one, to mate with up to three females in a single night, causing all to become pregnant. Different inbred strains have very different average times for recovery of libido, defined operationally as the time between attempted matings. DBA/2 mice can mate again within one hour, whereas B6 males usually wait for four days (Wimer and Fuller, 1966).

In some instances, one may want to maximize the rapid output of offspring from a single male. This situation could arise with rare genotypes such as new mutants or first generation transgenic founders. For this purpose, a single male can be rotated among sets of females (two or three per cage) in three or four cages. The factors that play a role in the length of each rotation have just been discussed: the length of the oestrus cycle, the time it takes for a male to recover a full sperm count, and the libido recovery time. Together, these factors suggest an optimal rotation period of four days in each cage. For full optimisation of offspring output, a male should receive two new eight-week-old virgin females in his cage every four days.

Fertilization
Fertilization takes place in the upper reaches of the oviduct (a region referred to as the ampulla). The egg remains viable for 10-15 hours after ovulation, although a gradual aging process slowly reduces the probability that fertilization will occur. Fertilization causes an immediate activation of the egg and induces the completion of the second meiotic division, which leads to the formation of the second polar body within two hours.

The actual process of fertilization can be divided into a series of highly ordered steps that lead ultimately to the joining of a single sperm cell with an ovulated egg (Wassarman, 1993). The first step in this process occurs with the binding of multiple spermatozoa to the zona pellucida, a thick extracellular coat that surrounds the egg. The association between the zona and the sperm surface triggers the acrosome reaction which affects an elongated sperm-specific membrane-bound organelle just below the surface that contains a specialized protease called acrosin. The acrosome reaction is a form of exocytosis that results in the complete loss of the plasma membrane overlying the acrosome in hybrid vesicles along with the outer acrosomal membrane. The acrosomal contents are released, and these allow the resulting "acrosome-reacted" sperm to use protease to digest its way through the zona pellucida to reach the perivitelline space between the zona and the egg plasma membrane. Finally, fusion occurs between the egg plasma membrane and the plasma membrane overlying the equatorial region of a single sperm cell. Fusion leads to the activation of the egg and the initiation of embryonic development.

The ultimate fusion reaction is not species-specific and can occur between heterologous gametes when the zona pellucida is first removed from the egg. Thus, in general, the main biochemical barrier to cross-species fertilization appears to lie within the initial interaction between the sperm plasma membrane and the egg zona pellucida. The specificity of this interaction implicates the existence of specific complementary molecules on egg and sperm, referred to respectively as the "sperm receptor" and the "egg binding protein" or EBP. The sperm receptor has been identified as a specific zona protein called ZP3 (Wassarman, 1990). The identity of the sperm surface EBP is still under investigation with multiple candidates described to date.

Postpartum Oestrus
Amazingly, within 28 hours of giving birth, a nursing mother will normally go into a postpartum oestrus that can allow her to become pregnant again immediately. There is a tendency to ovulate 12-18 hours after the time of birth, but this can be countered by the tendency to ovulate nocturnally (Bronson et al., 1966). The level of postpartum oestrus fertility is reduced somewhat relative to that achieved during a normal oestrus cycle. A postpartum pregnancy can have negative consequences for the litter already born as well as the one on the way. Since the mother is forced to split her resources between two sets of "progeny" her milk production will fall off more quickly than would otherwise be the case. In addition, the duration of the postpartum pregnancy can be extended for up to two weeks. Finally, when the second litter is born, there will be competition between the new pups and the older ones (if they are not yet weaned), and the new ones can suffer malnourishment or death.

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