Effects of fertility on gene expression and function of the bovine endometrium

Authors: MINTEN, MEGAN - Washington State University; BILBY, TODD - Texas Agrilife Research; BRUNO, RALPH G - West Texas A & M University; ALLEN, CAROLYN - Washington State University; Madsen, Crystal; WANG, ZEPING - Washington State University; SAWYER, JASON - Texas A&M University; TIBARY, AHMED - Washington State University; NEIBERGS, HOLLY - Washington State University; Geary, Thomas; BAUERSACHS, STEFAN - University Of Munchen; SPENCER, THOMAS - Washington State University

Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/12/2013
Publication Date: 8/5/2013
Publication URL: http://handle.nal.usda.gov/10113/57217
Citation: Minten, M.A., Bilby, T.R., Bruno, R.S., Allen, C.C., Madsen, C.A., Wang, Z., Sawyer, J.E., Tibary, A., Neibergs, H.L., Geary, T.W., Bauersachs, S., Spencer, T.E. 2013. Effects of fertility on gene expression and function of the bovine endometrium. PLoS One. 8(8):1-14 (e69444).

Interpretive Summary: Many domestic farm animals suffer from the same fertility problems as humans. Poor fertility is mainly due to embryonic death. The majority of embryonic loss occurs during the first three weeks of pregnancy in cattle and women. This pregnancy loss is due, in part, to inadequate support of embryo implantation by the female. To identify heifers that differed in fertility, 201 heifers were bred four times each and pregnancy determined. Heifers were then fertility classified based on pregnancy outcome from these matings. Heifers that were classified as highly fertile, subfertile or infertile were selected for further studies. The fertility-classified heifers received treatments for superovulation and were bred. Embryos were recovered on day 7 after estrus, evaluated, and then transferred to recipient cows. The number of embryos recovered and embryo quality did not differ between heifers. Pregnancy rates of recipient cows did not differ by heifer fertility classification. Estrus was again synchronized in heifers and 2 embryos were transferred into each heifer on day 7 after estrus. Pregnancy rates following embryo transfer were greater in high fertility classified heifers. The reproductive tracts of the fertility classified heifers were obtained on day 14 of the estrous cycle. No structural differences were observed in reproductive tracts of heifers. However, expression of genes from the uteri of fertility classified heifers differed greatly. These studies suggest that the uterus holds the key to heifers being inherently fertile.

Technical Abstract: Infertility and subfertility are important and pervasive reproductive problems in both domestic animals and humans. The majority of embryonic loss occurs during the first three weeks of pregnancy in cattle and women due, in part, to inadequate endometrial receptivity for support of embryo implantation. To identify heifers of contrasting fertility, serial rounds of artificial insemination (AI) were conducted in 201 synchronized crossbred beef heifers. The heifers were then fertility classified based on number of pregnancies detected on day 35 in four AI opportunities. Heifers, classified as having high fertility, subfertility or infertility, were selected for further study. The fertility-classified heifers were superovulated and flushed, and the recovered embryos were graded and then transferred to synchronized recipients. Quantity of embryos recovered per flush, embryo quality, and subsequent recipient pregnancy rates did not differ by fertility classification. Two in vivo-produced bovine embryos (stage 4 or 5, grade 1 or 2) were then transferred into each heifer on day 7 post-estrus. Pregnancy rates were greater in high fertility than lower fertility heifers when heifers were used as embryo recipients. The reproductive tracts of the classified heifers were obtained on day 14 of the estrous cycle. No obvious morphological differences in reproductive tract structures and histology of the uterus were observed in the heifers. Microarray analysis revealed differences in the endometrial transcriptome based on fertility classification. A genome-wide association study, based on SNP genotyping, detected 7 moderate associations with fertility across 6 different chromosomes. Collectively, these studies support the idea that innate differences in uterine function underlie fertility and early pregnancy loss in ruminants. Cattle with defined early pregnancy success or loss are useful to elucidate the complex biological and genetic mechanisms governing endometrial receptivity and uterine competency for pregnancy.