Abstract

Oxytocin (OT), a hypothalamic neuropeptide, applied through nasal approach (IAO), could improve maternal health during lactation that is disrupted by mother–baby separation; however, the regulation of IAO effects on maternal behaviors and lactation as well as the underlying mechanisms remain unclear. Using lactating rats, we observed effects of intermittent pup deprivation (PD) with and without IAO on maternal behaviors and lactation as well as the activity of OT neurons in the supraoptic nucleus (SON) and the activity of hypothalamic pituitary-adrenal axis, key factors determining the milk-letdown reflex during lactation and maternal behaviors. The results showed that PD reduced maternal behaviors and lactation efficiency of rat dams as indicated by significantly longer latency to retrieve their pups and low litter’s body weight gains during the observation, respectively. In addition, PD caused early involution of the mammary glands. IAO partially improved these changes in rat dams, which was not as significant as IAO effects on control dams. In the SON, PD decreased c-Fos and increased glial fibrillary acidic protein (GFAP) filaments significantly; IAO made PD-evoked c-Fos reduction insignificant while reduced GFAP filament significantly in PD dams. IAO tended to increase the levels of phosphorylated extracellular signal-regulated kinases (pERK) 1/2 in PD dams. Moreover, PD+IAO significantly increased plasma levels of dam adrenocorticotropic hormone and corticosterone but not OT levels. Lastly, PD+IAO tended to increase the level of corticotropin-releasing hormone in the SON. These results indicate that PD disrupts maternal behaviors and lactation by suppressing the activity of hypothalamic OT-secreting system through expansion of astrocytic processes, which are partially reversed by IAO through removing astrocytic inhibition of OT neuronal activity. However, the improving effect of IAO on the maternal health could be compromised by simultaneous activation of hypothalamic pituitary-adrenocortical axis.

Highlights

  • Lactation is essential for maintaining the species of mammals and an irreplaceable factor for mental and physical health of mothers and the babies

  • We first tested the effect of pup deprivation (PD) and IAO on maternal behaviors and lactation efficiency in 63 dams and assayed plasma hormone levels

  • IAO removed the trend of elongated latency of suckling in the PD group, but there was no statistical significance among the three groups [control: 11.5 (5.8, 24.3), n = 22; PD: 11.5 (8.3, 19.0), n = 16; PD+IAO: 8 (5, 21), n = 19, Kruskal–Wallis test, P > 0.05] (Figure 1Bb)

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Summary

Introduction

Lactation is essential for maintaining the species of mammals and an irreplaceable factor for mental and physical health of mothers and the babies. Lactation is vulnerable to many adverse factors, such as mother–baby separation (Wang and Hatton, 2009b), lacking social supports (Trickey and Newburn, 2014), obesity (Stuebe et al, 2014), babies’ sickness (Lawrence, 2013), poor breast conditions (Tang et al, 2013), cesarean section (Orun et al, 2010), mothers’ using drugs that are toxic to the babies (Varalda et al, 2012), early usages of bottle feeding and milk substitutes (Jiang et al, 2012), working requirements (Oslislo and Kaminski, 2000), and others (Seema et al, 1997; Berde and Yalcin, 2016) These factors often cause postpartum depression (Figueiredo et al, 2013) and insufficient breastfeeding (Stuebe et al, 2014), which are associated with high incidence of premenopausal breast cancer, diabetes, and obesity in the mothers and autism, sudden death, and deficiency in maternal behaviors in their offspring (Ip et al, 2007). Effects of PD and IAO on interactions of the two systems remain unclear, at the early stage of lactation

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