Effects of age, nursing, and oral IGF1 supplementation on neonatal porcine cervical development

Abstract

Nursing supports neonatal porcine uterine and testicular development, however, lactocrine effects on cervical development are undefined. Studies were conducted to determine the effects of i) age and the imposition of the lactocrine-null state from birth (postnatal day 0 (PND0)) by milk replacer feeding on cervical histology; ii) imposition of the lactocrine-null state for 2 days from birth on cervical cell proliferation, as reflected by proliferating cell nuclear antigen immunostaining; and iii) a single feeding of colostrum or milk replacer, administered at birth, with or without oral IGF1, on cervical cell proliferation and phosphorylated AKT (pAKT) and B-cell lymphoma 2 (BCL2) protein levels at 12 h postnatal. Cervical crypt depth and height of luminal epithelium (LE) increased with age by PND14, when both responses were reduced in replacer-fed gilts. Cell proliferation was reduced in LE at PND2, and in crypt epithelium and stroma by PND14 in replacer-fed gilts. Returning replacer-fed gilts to nursing on PND2 did not rescue the cervical phenotype by PND14. A single feeding of colostrum, but not milk replacer, was sufficient to support cervical cell proliferation at 12 h postnatal. IGF1 supplementation induced cell proliferation in replacer-fed gilts, and increased cervical pAKT and BCL2 levels in colostrum-fed gilts and replacer-fed gilts at 12 h postnatal. Results indicate that age and nursing support porcine cervical development, support is initiated at first ingestion of colostrum, IGF1 may be lactocrine-active, and identification of lactocrine-active factors can be accomplished by 12 h postnatal using this bioassay system.

Effects of colostrum, feeding method and oral IGF1 on porcine uterine development

“…See text for detailed descriptions of these relationships. (Camp et al 2014). Data presented here extend these findings by showing that a single feeding of colostrum at birth increased stromal cell nuclear density, as well as endometrial stromal and epithelial cell proliferation at 12 h. These responses were not reflected by associated changes in endometrial thickness or uterine expression of cell cycle or morphoregulatory transcripts.…”

“…Indeed, a single dose of colostrum at birth was sufficient to affect postnatal uterine development at 12 h, regardless of method of feeding colostrum. Further, results complement findings for the cervix (Camp et al 2014), indicating that oral IGF1 is bioactive during this period, as reflected by increased uterine cell proliferation. In fact, supplementation of milk-replacer with IGF1 rescued the lactocrine-null phenotype as reflected by PCNA immunostaining patterns.…”

“…Consistently, when colostrum consumption was delayed 0.5 h from birth or limited to 12 h from birth, markers of female reproductive tract (FRT) development, including uterine matrix metalloproteinase-9 (MMP9) and tissue inhibitor of metalloproteinase-1 (TIMP1), as well as cervical MMP9 expression levels on PND 2 were similar to those observed for nursed gilts that consumed colostrum continuously for 48 h from birth (Ho et al 2017). Further, a single feeding of colostrum at birth was sufficient to support normal levels of cervical cell proliferation at 12 h postnatal (Camp et al 2014). These observations, taken together with data indicating that nursing for as little as one hour from birth is sufficient to establish passive immunity in newborn piglets (Coalson & Lecce 1973), suggest that lactocrine signals supportive of FRT development are likely to be communicated within 12 h of birth (Bartol et al 2017).…”

“…Previous studies in the pig showed that nursing is necessary for normal development of porcine uterine (Miller et al 2013, Rahman et al 2016, cervical (Camp et al 2014), and testicular (Rahman et al 2014) tissues between birth and PND 2. Present results confirm and extend those findings for the uterus by showing that lactocrine effects on aspects of uterine development are detectable as early as 12 h postnatally.…”

“…Further, given that the first 12 h of neonatal life may represent a critical period for lactocrine programming of uterine function (Bagnell et al 2017), establishment of a model system for study of lactocrine-sensitive uterine organizational events specific to this period is important. Data specific to the developing porcine cervix during this neonatal period (Camp et al 2014) provide a framework and rationale for establishment of a similar protocol specific to the uterus. In refining that protocol for this purpose, three studies were conducted linked by a common 12-h bioassay design.…”