Alteration in the time and/or mode of delivery differentially modulates early development in mice

Abstract

Delivery is a complex biological process involving hormonal and mechanical stimuli that together condition the survival and development of the fetus out of the womb. Accordingly, changes in the time or way of being born are associated with an alteration of fundamental biological functions and hypothesized to promote the emergence of neurodevelopmental disorders. Hence, the steadily rise in preterm birth and cesarean section (CS) delivery rates over the past years has become a worldwide health concern. In our previous work, we reported that even though no long-term autistic-like deficits were observed, mice born preterm by CS presented early transient neuronal and communicative defects. However, understanding if these alterations were due to an early birth combined with CS delivery, or if prematurity solely could lead to a similar outcome remained to be evaluated. Using mice born either at term or preterm by vaginal or CS delivery, we assessed early life ultrasonic vocalizations and the onset of eye opening. We report that alterations in communicative behaviors are finely attuned and specifically affected either by preterm birth or by the association between CS delivery and preterm birth in mice, while delayed onset of eye opening is due to prematurity. Moreover, our work further underlies a gender-dependent vulnerability to changes in the time and/or way of being born with distinct outcomes observed in males and females. Thus, our results shed light on the intricacy of birth alterations and might further explain the disparities reported in epidemiological studies.

Lasting consequences on physiology and social behavior following cesarean delivery in prairie voles

“…Previous work in mice has found that CS pups either produce more calls on PND-9 [45][46][47] or produce an equivalent number of calls to VD counterparts [40,48] or USVs with decreased amplitudes [40], however, these studies were all in mice at a later stage of development than the current work. Our prior study of VD vole pups on PNDs 1 and 4 found that exposure to prenatal OXT led to increased USV production [34].…”

“…Previous work in mice has found that CS pups either produce more calls on PND-9 (Chiesa et al, 2020(Chiesa et al, , 2019Morais et al, 2020) or produce an equivalent number of calls (Castillo-Ruiz et al, 2018;Morais et al, 2021) or USVs with decreased amplitudes (Castillo-Ruiz et al, 2018) compared to VD counterparts, however, these studies were all in mice at a later stage of development than the current work. Our prior study of VD vole pups on PNDs 1 and 4 found that exposure to prenatal OXT led to increased USV production (Kenkel et al, 2019b).…”

Birth signalling hormones and the developmental consequences of caesarean delivery

“…However, two other studies failed to find any association between birth mode and infant behaviour or CORT response to heel sticks during this time period 192,193 . In mice, CS results in pups emitting quieter isolation‐induced distress vocalisations 194 ; however, other studies have found CS results in greater vocalisation when tested later in development 195,196 . Further beyond birth, CS‐delivered human newborns show HPA‐axis hypo‐reactivity in the first few months postnatally 45,197 .…”

“…192,193 In mice, CS results in pups emitting quieter isolation-induced distress vocalisations 194 ; however, other studies have found CS results in greater vocalisation when tested later in development. 195,196 Further beyond birth, CS-delivered human newborns show HPA-axis hypo-reactivity in the first few months postnatally. 45,197 We do not yet know the effects of birth mode on the HPA-axis, nor stress reactivity in childhood or further into development.…”

Selective reduction in the expression of type‐1 metabotropic glutamate receptors in the hippocampus of adult rats born by caesarean section

“…To our knowledge, no specific studies on the long term effects of C‐section on hippocampal‐dependent behaviour or hippocampal‐dependent synaptic plasticity have been performed so far. The only changes reported to date refer to early transient underdevelopment of dendritic arbour, associated to very mild variation of ultrasound vocalisation at postnatal day 9 (Chiesa et al., 2019, 2020). The present findings suggest that the long term consequences of mode of delivery require further studies as they might have also potential implications for investigating the etiopathogenesis of other CNS disorders.…”