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theses

Nursing ensures lactocrine delivery of milk-borne bioactive factors to offspring and the lactocrine hypothesis for maternal programming proposes that disruption of lactocrine communication from birth (postnatal day = PND 0) affects both the program and trajectory of porcine uterine development. Establishment of a model system for study of lactocrine-sensitive uterine organizational events shortly after birth in the neonate and for identification of potentially lactocrine-active factors found in porcine colostrum, such as insulin-like growth factor 1 (IGF1), is important. Studies show that the neonatal porcine uterine transcriptome is age- and lactocrine-sensitive on PND 2. However, whether uterine microRNA (miRNA) expression or the uterine miRNA-mRNA interactome is affected similarly is unknown. Lactocrine deficiency from birth, reflected by low serum immunoglobulin immunocrit, was associated with alterations in aspects of the neonatal uterine developmental program and, long-term, was linked to reduced lifetime fecundity in adult gilts. These observations suggested lactocrine effects on programming of adult uterine function. However, whether lactocrine deficiency and disruption of neonatal uterine development is ultimately reflected by effects on patterns of endometrial gene expression during the periattachment period of early pregnancy in adulthood is unknown. Consequently, research objectives were to: (1) determine acute effects of (a) nursing vs milk replacer feeding, and (b) method of feeding a single dose of colostrum at birth, with or without supplemental IGF1, on porcine uterine development at 12 h postnatally; (2) determine short-term effects of age and nursing on porcine uterine (a) miRNA expression between birth and PND 2 and (b) miRNA-mRNA interactions using integrated target prediction analysis; and (3) determine long-term effects of lactocrine-deficiency from birth on adult endometrial (a) mRNA and miRNA expression during the periattachment period of early pregnancy (pregnancy day 13), including identification of affected miRNA–mRNA interactions. Results showed nursing for 12 h from birth supports rapid establishment of a uterine developmental program, and that a single feeding of colostrum at birth increased endometrial cell proliferation at 12 h, regardless of method of feeding. Further, oral IGF1 was sufficient to support endometrial cell proliferation at 12 h in replacer-fed gilts, and supplementation of colostrum with IGF1 further increased endometrial cell proliferation. Between birth and PND 2, novel age- and lactocrine-sensitive uterine miRNAs and miRNA-mRNA relationships associated with porcine neonatal development were identified. On pregnancy day 13, lactocrine deficiency from birth did not affect corpora lutea number, uterine horn length, uterine wet weight, embryo recovery, or uterine luminal fluid estrogen content. However, next-generation sequencing analyses revealed lactocrine-sensitive endometrial mRNAs and miRNAs associated with aspects of solute transport, endometrial receptivity, and immune response. Collectively, results showed that adequate colostrum consumption within 12-24 hours of birth in pigs is important for establishment of a uterine developmental program required to insure normal patterns of endometrial gene expression during the periattachment period of early pregnancy.

ETD_8747

Ph.D.

Includes bibliographical references

by Ashley George

doi:10.7282/T3BV7M2T

ETD doctoral

The author owns the copyright to this work.