Neonatal lactocrine deficiency affects the adult porcine endometrial transcriptome at pregnancy day 13

Authors: GEORGE, ASHLEY - Rutgers University; HO, TEH-YUAN - Rutgers University; PRASAD, NRIPESH - Hudsonalpha Institute For Biotechnology; Keel, Brittney; Miles, Jeremy; Vallet, Jeff; BARTOL, FRANK - Auburn University; BAGNELL, CAROL - Rutgers University

Submitted to: Biology of Reproduction
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/8/2018
Publication Date: 1/1/2019
Citation: George, A.F., Ho, T., Prasad, N., Keel, B.N., Miles, J.R., Vallet, J.L., Bartol, F.F., Bagnell, C.A. 2019. Neonatal lactocrine deficiency affects the adult porcine endometrial transcriptome at pregnancy day 13. Biology of Reproduction. 100(1):71-85. https://doi.org/10.1093/biolre/ioy180.
DOI: https://doi.org/10.1093/biolre/ioy180

Interpretive Summary: Female pigs enduring lactocrine deficiency (i.e., suboptimal delivery of milk-borne bioactive factors to nursing mammals) have permanently impaired reproductive performance as adults. Although the exact mechanism by which reduced reproductive efficiency of females that have not obtained adequate colostrum following birth are not known, evidence from pre-pubertal females with sub-optimal lactocrine support suggests altered function of the uterine endometrium. Therefore, this study evaluated endometrial gene expression during the critical periattachment period of early pregnancy in littermate females following sub-optimal or optimal lactocrine support during early life, as reflected by low versus high serum immunoglobulin immunocrit (iCrit; indirect measure of colostrum intake). This study identified many (1157) differentially expressed endometrial mRNAs in high vs. low iCrit gilts. The identified genes are involved in many critical biological functions during the periattachment period such as epithelial cell transport mechanisms, prostaglandin synthesis and secretion, immune response, endometrial receptivity, uterine remodeling, and miRNA-mRNA interactions. These results demonstrate that adequate colostrum consumption during early life is necessary for establishment of a normal uterine developmental program and provide biological mechanisms to explain impaired reproductive performance of female pigs that have endured lactocrine deficiency during early life.

Technical Abstract: Reproductive performance of female pigs that do not receive sufficient colostrum from birth is permanently impaired. Whether lactocrine deficiency, reflected by low serum immunoglobulin immunocrit (iCrit), affects patterns of endometrial gene expression during the periattachment period of early pregnancy is unknown. Here, objectives were to determine effects of low iCrit at birth on the adult endometrial transcriptome on pregnancy day (PxD) 13. On the first day of postnatal life, gilts were assigned to high or low iCrit groups. Adult high (n = 8) and low (n = 7) iCrit gilts were bred (PxD 0), humanely slaughtered on PxD 13 when tissues and fluids were collected. The endometrial transcriptome was defined for each group using mRNAseq and microRNAseq. Reads were mapped to the Sus scrofa 11.1 genome build. Mature microRNAs were annotated using miRBase 21. Differential expression was defined based on fold change (= ± 1.5). Lactocrine deficiency did not affect corpora lutea number, uterine horn length, uterine wet weight, conceptus recovery, or uterine luminal fluid estrogen content on PxD 13. However, mRNAseq revealed 1157 differentially expressed endometrial mRNAs in high versus low iCrit gilts. Differentially expressed genes had functions related to solute transport, endometrial receptivity, and immune response. Six differentially expressed endometrial microRNAs included five predicted to target 62 differentially expressed mRNAs, affecting similar biological processes. Thus, lactocrine deficiency on the first day of postnatal life can alter uterine developmental trajectory with lasting effects on endometrial responses to pregnancy as reflected at the level of the transcriptome on PxD 13.