Placental genotype affects early postpartum maternal behaviour

Abstract

The mammalian placenta is a source of endocrine signals that prime the onset of maternal care at parturition. While consequences of placental dysfunction for offspring growth are well defined, how altered placental signalling might affect maternal behaviour is unstudied in a natural system. In the cross between sympatric mouse species, Mus musculus domesticus and Mus spretus , hybrid placentas are undersized and show misexpression of genes critical to placental endocrine function. Using this cross, we quantified the effects of placental dysregulation on maternal and anxiety-like behaviours in mice that differed only in pregnancy type. Relative to mothers of conspecific litters, females exposed to hybrid placentas did not differ in anxiety-like behaviours but were slower to retrieve 1-day-old pups and spent less time in the nest on the night following parturition. Early deficits in maternal responsiveness were not explained by reduced ultrasonic vocalization production in hybrid pups and there was no effect of pup genotype on measures of maternal behaviour and physiology collected after the first 24 h postpartum. These results suggest that placental dysregulation leads to poor maternal priming, the effect of which is alleviated by continued exposure to pups. This study provides new insight into the placental mediation of mother–offspring interactions.

Placental effects on the maternal brain revealed by disrupted placental gene expression in mouse hybrids

“…However, maternal-placental communication genes co-expressed in maternal brain and placenta show elevated evolutionary rates, consistent with antagonistic coevolutionary processes. The expression of a proportion of transcripts of these genes from a foreign paternal genome in the placenta has the potential to affect the maternal brain and explain postpartum effects on maternal behaviour [33]. In addition to the effects of placental disruption on the maternal brain, expression differences between the parental species in this hybrid system reveal an unanticipated influence of the placenta's paternal genome on the maternal brain.…”

“…Although Peg3 was not misexpressed in the hybrid placenta, the transgressively overexpressed MEG, Phlda2, was recently shown to perturb maternal behaviour and neural gene expression when its dosage was altered in mouse placenta [8]. In particular, overexpression of placental Phlda2 reduced postpartum nurturing behaviour [8], an effect of a single gene manipulation that is strikingly similar to early postpartum deficits in maternal behaviour in Dom mothers of hybrid litters [33]. Since Phlda2 and Ascl2 jointly regulate the development of the endocrine compartment [19], it is likely that transgressive misexpression of both genes in hybrid placenta impacts the maternal brain via effects on placental hormone expression.…”

“…We recently showed that maternal responsiveness to pups is significantly altered in Dom females with newborn hybrid relative to conspecific litters [33]. These effects of litter genotype were only detected during the first 24 h postpartum, suggesting that altered behaviour in mothers of hybrid litters is the residual consequence of abnormal placental signalling rather than a response to phenotypic differences between hybrid and conspecific pups [33]. Here, by comparing MPoA expression between females of the same species that differ only in the type of pregnancy/placenta they experience (hybrid versus conspecific), we specifically isolate the effect of placental gene expression differences on the maternal brain (electronic supplementary material, figure S1).…”

Haldane's rule in the placenta: Sex‐biased misregulation of the Kcnq1 imprinting cluster in hybrid mice

“…1996), and exhibit altered neural gene expression at e17.5 (Arévalo and Campbell 2020) and reduced maternal behavior immediately postpartum (Gardner et al. 2019). These observations suggest that hybrid pregnancy disrupts maternal homeostasis and, in this sense, is a physiological stressor.…”

Haldane’s rule in the placenta: sex-biased misregulation of theKcnq1imprinting cluster in hybrid mice

“…However, 590 the immediate consequences of an adverse intrauterine environment are generally more severe in 591 males, with more pronounced placental pathology and intrauterine growth restriction, and a 592 higher rate of mortality for male fetuses (Cooperstock and Campbell 1996;Walker et al 2012;593 Sandman et al 2013;Davis and Pfaff 2014). Female M. m. domesticus carrying hybrid litters are 594 potentially exposed to altered placental endocrine signaling due to deficits in spongiotrophoblast 595 cells in hybrid placentas (Zechner et al 1996), and exhibit altered neural gene expression at 596 e17.5 (Arévalo and Campbell 2020) and reduced maternal behavior immediately postpartum 597 (Gardner et al 2019). These observations suggest that hybrid pregnancy disrupts maternal 598 homeostasis and, in this sense, is a physiological stressor.…”