Identification of Beef Heifers with Superior Uterine Capacity for Pregnancy

Abstract

Infertility and subfertility represent major problems in domestic animals and humans, and the majority of embryonic loss occurs during the first month of gestation that involves pregnancy recognition and conceptus implantation. The critical genes and physiological pathways in the endometrium that mediate pregnancy establishment and success are not well understood. In study one, predominantly Angus heifers were classified based on fertility using serial embryo transfer to select animals with intrinsic differences in pregnancy loss. In each of the four rounds, a single in vitro-produced, high-quality embryo was transferred into heifers on Day 7 postestrus and pregnancy was determined on Days 28 and 42 by ultrasound and then terminated. Heifers were classified based on pregnancy success as high fertile (HF), subfertile (SF), or infertile (IF). In study two, fertility-classified heifers were resynchronized and bred with semen from a single high-fertility bull. Blood samples were collected every other day from Days 0 to 36 postmating. Pregnancy rate was determined on Day 28 by ultrasound and was higher in HF (70.4%) than in heifers with low fertility (36.8%; SF and IF). Progesterone concentrations in serum during the first 20 days postestrus were not different in nonpregnant heifers and also not different in pregnant heifers among fertility groups. In study three, a single in vivo-produced embryo was transferred into fertility-classified heifers on Day 7 postestrus. The uteri were flushed on Day 14 to recover embryos, and endometrial biopsies were obtained from the ipsilateral uterine horn. Embryo recovery rate and conceptus length and area were not different among the heifer groups. RNA was sequenced from the Day 14 endometrial biopsies of pregnant HF, SF, and IF heifers (n = 5 per group) and analyzed by edgeR-robust analysis. There were 26 differentially expressed genes (DEGs) in the HF compared to SF endometrium, 12 DEGs for SF compared to IF endometrium, and three DEGs between the HF and IF endometrium. Several of the DEG-encoded proteins are involved in immune responses and are expressed in B cells. Results indicate that preimplantation conceptus survival and growth to Day 14 is not compromised in SF and IF heifers. Thus, the observed difference in capacity for pregnancy success in these fertility-classified heifers is manifest between Days 14 and 28 when pregnancy recognition signaling and conceptus elongation and implantation must occur for the establishment of pregnancy.

Aspects of embryo-maternal communication in establishment of pregnancy in cattle

“…While the differences in conceptus length are due, at least in part, to intrinsic differences in the embryo/conceptus, likely related to oocyte quality, it would be wrong to completely discount a role for the uterus in contributing to variation in conceptus length and pregnancy establishment. Using a model of repeated embryo transfer originally described by McMillan et al (1999), Geary et al (2016) classified heifers based on pregnancy success following serial embryo transfer as high fertile (HF), subfertile (SF), or infertile (IF). Conceptus survival and growth to Day 14 was not compromised in SF and IF heifers.…”

A comparison of the uterine proteome of mares in oestrus and dioestrus

“…Of the proteins more abundant in oestrus, two may have immune functions: IGLL1 and A1BG. The protein IGLL1 is an immunoglobulin chain expressed by plasma cells in various tissues including the uterus (Geary et al, 2016;Moran, Butler, Moore, MacHugh, & Creevey, 2017), but its role in the equine endometrium has not been characterized. However, it has been detected in the cervical mucus plug of pregnant mares (Loux, Scoggin, Troedsson, Squires, & Ball, 2017).…”

“…In humans, the IGLL1 gene is expressed only in pre-B cells and positively impacts B-cell development (Bauer, McDermid, Budarf, Keuren, & Blomberg, 1993). Greater endometrial expression of the IGLL1 gene was reported in dairy cows with strong genetic merit for fertility compared to those with poor genetic merit (Geary et al, 2016;Moran et al, 2017). Future studies are required to determine whether there is any association of IGLL1 with fertility in mares.…”

Genomic Analysis of Spontaneous Abortion in Holstein Heifers and Primiparous Cows

“…Consequently, in Holstein cattle, conception rate has improved approximately 6 percentage points in heifers and 11 percentage points in cows since its inclusion in selection indexes in 2010 [13,14]. Although more recent studies have focused on the more prevalent early embryonic loss [15][16][17][18], additional research investigating fetal loss is needed, as very little is known about the genomic structure and physiological mechanisms responsible. In order to improve upon that knowledge, it is necessary to understand which genomic regions, genes, gene-sets, and pathways are associated with SA.…”