Definition

Whenever a pup is killed by its parent or an unrelated mouse, it is considered to be a case of infanticide or infanticidal behavior. Infanticide is a complex behavior and many theories exist attempting to explain it.

Description

In the laboratory, infanticide is a maladaptive, abnormal maternal behavior. The mother may perform infanticide shortly after giving birth.

Other mice can also perform infanticide such as the pups’ father or an unrelated male or female mouse.

Infanticide is distinctly different from passive cannibalism. The former refers to the killing of a pup while the latter refers to eating a pup (which could have already been dead from other causes, such as stillbirth).

Factors Influencing Infanticide Incidence

  • Housing conditions: Housing conditions and genetics are known to be involved in the emergence of this behavior. Overly packed conditions are associated with an increased risk of infanticide.
  • Birth asynchrony: When female mice are sharing a communal nest, infanticide rises when there are instances of reproductive asynchrony (deliveries occurring at different times), suggesting a temporal dynamic of infanticide.
  • Castration: When male mice are castrated, they are significantly less likely to perform infanticide on pups.

Behavioral Variants of Infanticide

Parental Infanticide

As the term implies, parental infanticide specifically refers to the moment that a parent mouse kills its own genetically related pup.

Non-Parental Infanticide

Non-parental infanticide, on the other hand, is committed by a male or female mouse which is unrelated to the pup.

Function of the Infanticide Behavior

  • To increase their own pups’ chance for survival: Recent research is making the argument that non-parental infanticide may be an adaptive behavior. Male (or female) mice which perform infanticide on other mice’s pups invariably increase their own chances for reproductive success. By killing others’ pups, there will be more resources available for their own pups, thus increasing the chance of survival.
  • To reduce overcrowding: Infanticide is also exhibited during stressful or overcrowded conditions. By killing their own pups, mothers are ensuring their own survival during tough times when resources are limited, in order to get a chance to reproduce at a later point in time.

Application of Infanticide

  • Overly cold temperatures: Cold temperatures trigger parental infanticide. It is hypothesized that this may occur due to environmental influence altering hypothalamic homeostasis.
  • Presence of foreign odors: Pregnant mothers will kill their pups if the environment they are in contains foreign odors, such as odors from unknown males’ urine or excrement.
  • Overcrowded housing: Parental and non-parental infanticide are more likely to occur in overcrowded housing conditions.
  • In proximity to a pup: Mice may exhibit infanticide when in close proximity to a young pup. Depending on gender and strain, the frequency of the behavior will vary.

Behavioral Tests for Assessing Infanticide

  • Parental behavior test: In the parental behavior test, mice are tested for their parental behavior instincts. One day before the test, a mouse is provided with extra material (such as cotton), in order to make a nest. Then, the next day, a newborn pup is placed in the corner of the cage that is far away from the nest. The experimental mouse is measured by its reaction, whether it retrieves the pups, ignores it, or attacks (and kills) it. Typically, foster pups are used for this test. However, it is also possible to use pups which are genetically related to the test subject.
  • Video recording: Since infanticide can occur at any point, constant video surveillance is necessary, in order to capture the moment. Otherwise, researchers run the risk of misclassifying the behavior. For example, passive cannibalism is often mistaken for infanticide which is a completely different behavior with different motivations. Therefore, video recording is absolutely necessary, in order to observe the situation in which the death occurred, in case it happens while the researchers are absent. Also, video technology makes it possible to distinguish whether it was parental or non-parental infanticide that occurred.

Pharmaceutical Findings

Oxytocin Reduces Infanticide

It is estimated that roughly 60 to 90% of female house mice will kill unrelated pups.  Subcutaneous and intracerebroventricular injections of oxytocin are able to significantly lower infanticidal behavior, possibly by acting directly on the central nervous system.

Mouse Strains Exhibiting Infanticide Behavior

C57BL/6J Mice Exhibit High Levels of Infanticide

C57BL/6J mice are known to be highly prone to killing unknown young pups. The degree with which C57BL/6J male mice perform infanticide varies with age, beginning to be significantly more aggressive than other strains when they are as young as 35 days old. The tendency for infanticide significantly lowers when C57BL/6J males are castrated.

Similar findings exist for female C57BL/6J mice, averaging a 60% chance of exhibiting infanticide.

DBA/2J Mice Exhibit Low Levels of Infanticide

Infanticide is much lower in the DBA/2J male mice than the C57BL/6J male mouse strain. In fact, adult DBA/2J mice, when they are in their prime, kill as many pups as C57BL/6J when they are only 2 months of age.

More comparisons need to occur across mouse strains and genders, such as between female DBA/2J and C57BL/6J mice, in order to establish behavioral parameters.

Abnormalities of Infanticide Behaviors

GPR40/FFAR1 Deletion Increases Infanticide

The free fatty acid receptor 1 (GPR40/FFAR1) is activated by docosahexaenoic acids (DHA) and other polyunsaturated fatty acids (PUFAs) in the central nervous system. Mice which lack this receptor have altered maternal behavior and higher instances of infanticide when compared to wild-type controls.

ERKO Male Mice Exhibit High Infanticide

The α type of estrogen receptor (ERα) is involved in testosterone-related male reproductive behaviors. ER knockout mice (ERKO) are deficient in ERα but still have ERβ intact. Compared to wild-type control mice, ERKO male mice exhibit much higher levels of infanticide (about 30% and 70%, respectively). After a gonadectomy, the ERKO infanticide decreases to the level of normal wild-type controls.

ArKO Males Have High Infanticide Rate

Brain aromatase (P450arom) is an enzyme with an important role in estrogen biosynthesis. It has been established that genetically modified male mice with the aromatase gene disrupted at exons 1 and 2 (ArKO mice) show a high likelihood of infanticide toward pups. ArKO mice also showed deficits in sexual behaviors towards estrous females. Thus, P450arom is somehow related to adaptive parental behavior and successful sexual behaviors.

PRKO Males Display Low Infanticide

Male mice with the progesterone receptor knocked out (PRKO) do not exhibit infanticidal behavior and are minimally aggressive towards pups. PRKO mice, however, still retain levels of aggression towards other adult male PRKO during the Resident-Intruder Test, suggesting the lack of aggression in PRKO mice is specific to pups.

Disease Models Using Infanticide Behavior

Gabrd−/− Mice Model Postpartum Psychosis

The Gabrd−/− mouse strain is commonly used for modeling postpartum psychosis. In this model, high rates of infanticide are said to be indicative of the disease’s phenotype. Current research is geared towards determining whether this mouse strains may also be used to study postpartum depression.

Summary

  • Whenever a pup is killed by a parent or unrelated mouse, it is known as infanticide.
  • Passive cannibalism is often mistaken for infanticide which is a completely different behavior with different motivations.
  • Housing conditions and genetics are known to be involved in the emergence of this behavior, as well as stressors. Also, birth asynchrony increases the likelihood of infanticide.
  • Castration decreases males’ infanticidal behavior.
  • Infanticide can be parental or non-parental.
  • Infanticide may serve the purpose of reducing overcrowding and ensuring a mouse’s own survival during stressed times (i.e. limited resources).
  • The presence of foreign odors, such as from male fecal matter, can also trigger pregnant mothers exposed to the odor to commit infanticide upon giving birth.
  • The parental behavior test is used to assess parental tendencies in mice and compares parental behavior with the frequency of aggression (i.e. infanticide) and/or ignoring.
  • Video recording is used in order to monitor mice and distinguish between infanticide and passive cannibalism.
  • Oxytocin reduces infanticide in female mice.
  • C57BL/6J mice are known to be highly prone towards killing young pups while DBA/2J display low levels of infanticide.
  • Deletion of the GPR40/FFAR1 receptor which is activated by DHA is also associated with higher infanticidal rates.
  • Infanticide is increased in ERKO and ArKO male mice which are genetically modified to lack the estrogen receptor and aromatase enzyme, respectively.
  • PRKO mice display low levels of infanticide while their aggression levels towards adult males remain comparable to healthy controls’.
  • The Gabrd−/− mouse strain displays high levels of infanticide and is commonly used for modeling postpartum psychosis.

References

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  9. McCarthy, Margaret M., Jane E. Bare, and Frederick S. Vom Saal. “Infanticide and parental behavior in wild female house mice: effects of ovariectomy, adrenalectomy and administration of oxytocin and prostaglandin F2 alpha.” Physiol Behav 36.1 (1986): 17-23.
  10. Aizawa, Fuka, et al. “The deletion of GPR40/FFAR1 signaling damages maternal care and emotional function in female mice.” Biological and Pharmaceutical Bulletin 40.8 (2017): 1255-1259.
  11. Ogawa, Sonoko, et al. “Modifications of testosterone-dependent behaviors by estrogen receptor-α gene disruption in male mice.” Endocrinology 139.12 (1998): 5058-5069.
  12. Matsumoto, Takahiro, Shin-ichiro Honda, and Nobuhiro Harada. “Alteration in sex-specific behaviors in male mice lacking the aromatase gene.” Neuroendocrinology 77.6 (2003): 416-424.
  13. Schneider, Johanna S., et al. “Progesterone receptors mediate male aggression toward infants.” Proceedings of the National Academy of Sciences 100.5 (2003): 2951-2956.
  14. Maguire, Jamie, and Istvan Mody. “Behavioral deficits in juveniles mediated by maternal stress hormones in mice.” Neural plasticity 2016 (2016).

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