The pre-hatching bovine embryo transforms the uterine luminal metabolite composition in vivo

Abstract

In cattle, conceptus development after elongation relies on well-characterized, paracrine interactions with the hosting maternal reproductive tract. However, it was unrecognized previously that the pre-hatching, pre-implantation bovine embryo also engages in biochemical signalling with the maternal uterus. Our recent work showed that the embryo modified the endometrial transcriptome in vivo . Here, we hypothesized that the embryo modulates the biochemical composition of the uterine luminal fluid (ULF) in the most cranial portion of the uterine horn ipsilateral to the corpus luteum. Endometrial samples and ULF were collected post-mortem from sham-inseminated cows and from cows inseminated and detected pregnant 7 days after oestrus. We used quantitative mass spectrometry to demonstrate that the pre-hatching embryo changes ULF composition in vivo . Embryo-induced modulation included an increase in concentrations of lipoxygenase-derived metabolites [12(S)-HETE, 15(S)-HETE] and a decrease in the concentrations of amino acids (glycine), biogenic amines (sarcosine), acylcarnitines and phospholipids. The changed composition of the ULF could be due to secretion or depletion of specific molecules, executed by either the embryo or the endometrium, but initiated by signals coming from the embryo. This study provides the basis for further understanding embryo-initiated modulation of the uterine milieu. Early embryonic signalling may be necessary to guarantee optimal development and successful establishment of pregnancy in cattle.

Evaluation of the factors that affect the pregnancy rates during embryo transfer in beef heifers

“…Normally the embryo reaches from the oviduct into the uterus approximately 6–8 days after fertilization (Bilodeau‐Goeseels & Kastelic, ). Therefore, in uterine flushings on day 7, embryos are mostly collected from the cranial part of the uterine horn (Gordon, ; Niemann & Wrenzycki, ; Sponchiado et al, ). Therefore, it is recommended to transfer the embryos to the cranial part of the uterine horn.…”

The incompletely fulfilled promise of embryo transfer in cattle—why aren’t pregnancy rates greater and what can we do about it?

“…The bovine embryo, too, can signal the mother and as early as day 7 of gestation. The local presence of the embryo causes changes in abundance of specific endometrial transcripts ( Sponchiado et al, 2017 ) and in the metabolome of the uterine lumen ( Sponchiado et al, 2019 ). An example of embryo-induced changes in the uterine fluid metabolome and associated changes in uterotubal gene expression is illustrated in Figure 5 .…”

“…Consequences of local actions of the blastocyst on the endometrium for long-term function of the blastocyst remain to be determined. The figure is reproduced from Sponchiado et al (2019) and is reproduced from Scientific Reports through a Creative Commons Attribution 4.0 International License.…”

Effect of Exposure to Seminal Plasma Through Natural Mating in Cattle on Conceptus Length and Gene Expression

“…Despite the molecular complexity underlying the critical processes that take place in the periconception and early preimplantation period, the success of in vitro reproductive techniques suggests that the requirements of the embryo can be met by a relative simple set of media, and that embryonic development, at least to the blastocyst stage, occurs independently of interaction with the female reproductive tract. While blastocyst stage embryos can induce changes in the endometrium (Sponchiado et al, 2017;Passaro et al, 2018Passaro et al, , 2019 as well as the uterine lumen metabolite composition (Sponchiado et al, 2019), mainly through embryo-derived interferon-tau (Passaro et al, 2019), whether this interaction plays an important role in embryo survival is questionable given the fact that embryos can be transferred to a virgin uterus as late as Day 16 and still establish a pregnancy (Betteridge et al, 1980). Nonetheless, it is becoming apparent that offspring health can be affected by the environmental conditions experienced during gamete maturation, embryo development and fetal growth (Hanson and Gluckman, 2014).…”