Early life adoption shows rearing environment supersedes transgenerational effects of paternal stress on aggressive temperament in the offspring

Abstract

Prenatal experience and transgenerational influences are increasingly recognized as critical for defining the socio-emotional system, through the development of social competences and of their underlying neural circuitries. Here, we used an established rat model of social stress resulting from male partner aggression induced by peripubertal (P28-42) exposure to unpredictable fearful experiences. Using this model, we aimed to first, characterize adult emotionality in terms of the breadth of the socio-emotional symptoms and second, to determine the relative impact of prenatal vs postnatal influences. For this purpose, male offspring of pairs comprising a control or a peripubertally stressed male were cross-fostered at birth and tested at adulthood on a series of socio-emotional tests. In the offspring of peripubertally stressed males, the expected antisocial phenotype was observed, as manifested by increased aggression towards a female partner and a threatening intruder, accompanied by lower sociability. This negative outcome was yet accompanied by better social memory as well as enhanced active coping, based on more swimming and longer latency to immobility in the forced swim test, and less immobility in the shock probe test. Furthermore, the cross-fostering manipulation revealed that these adult behaviors were largely influenced by the post- but not the prenatal environment, an observation contrasting with both pre- and postnatal effects on attacks during juvenile play behavior. Adult aggression, other active coping behaviors, and social memory were determined by the predominance at this developmental stage of postnatal over prenatal influences. Together, our data highlight the relative persistence of early life influences.

Fig. 1. Schematic of the experimental procedure and cross-fostering of pups.

A Timeline of experimental procedure on F0 generation males and cross-fostering of pups. Orange arrow, start of behavioral experiments on F1 generation. See Supplementary figure 1 for a detailed description of the behavioral tests performed on F0 males. B Experimental timeline of behavioral tests performed on the F1 males. C For cross-fostering, the pups were divided into four groups—(i) Control–Control - born to and raised by the same dam, paired with a control male, (ii) Control-PPS—born to a dam paired with a PPS male, but fostered with a dam paired with a control male, (iii) PPS-Control—born to a dam paired with a control male, but fostered with a dam paired with a PPS male and (iv) PPS–PPS—born to, and raised by the same dam, paired with a PPS male.

Fig. 2. Postnatal environment explains aggressive tendencies in F1 males.

A Play behavior. In juveniles, aggressive temperament was enhanced during home cage play behavior as a result of both prenatal and postnatal PPS dam influences. Prenatal effects are depicted by letters a, b. B Cohabitation. Only the adults reared by PPS male-paired dams exhibited increased aggressive behavior towards females during cohabitation. C Resident-intruder test. Adults reared by PPS male-paired dams exhibited increased aggressive behavior towards an intruder male as evidenced through increased proportion of offensive behaviors compared to all other behaviors. D Increased aggression in males reared by PPS male-paired dams was also measured in terms of the number of offensive events. The results are the mean ± s.e.m. PPS: Peripubertally stressed rats. * P < 0.05, ** P < 0.01.

Fig. 3. Offspring of PPS males show a lower inclination for social contact.

A Social Preference. The exploration percentage (expressed as the time spent exploring the juvenile over total exploration) was significantly reduced both by being born to or reared by PPS male-paired dams. Prenatal effects are depicted by letters a, b. B The total time spent exploring the juvenile was significantly reduced by both prenatal and postnatal effects, while there was no effect on object exploration time. Prenatal effects are depicted by letters a, b. C Social memory. Social memory was enhanced in pups raised by PPS male-paired dams as evident by greater novel juvenile exploration percentage when compared to total exploration time. D The effect in social memory was driven by decreased exploration of the familiar juvenile by offspring raised by PPS male-paired dams, with no changes in exploration of the novel juvenile. n = 8 per group. The results are the mean ± s.e.m. PPS: Peripubertally stressed rats. * P < 0.05, ** P < 0.01, *** P < 0.001.

Fig. 4. Adults raised by PPS male-paired dams display enhanced coping behaviors.

A Shock probe, passive coping—the pups born to or raised by PPS male-paired dams exhibited less immobility in response to the shock and increased rearing. B Shock probe, active coping—no significant difference was observed in pups reared by PPS male-paired dams in terms of probe burying or probe exploration. C Forced swim test. The pups raised by PPS male-paired dams showed more active coping by a postnatal increase in the time spent swimming. D The increase in swimming duration was accompanied by a postnatal effect on the latency to float. n = 8 per group. The results are the mean ± s.e.m. Ctrl: Control, PPS: Peripubertally stressed rats. * P < 0.05, ** P < 0.01, *** P < 0.001.