Lethal variants of equine pregnancy: is it the placenta or foetus leading the conceptus in the wrong direction?

Abstract

Embryonic and foetal loss remain one of the greatest challenges in equine reproductive health with 5-10% of established day 15 pregnancies and a further 5-10% of day 70 pregnancies failing to produce a viable foal. The underlying reason for these losses is variable but ultimately most cases will be attributed to pathologies of the environment of the developing embryo and later foetus, or a defect intrinsic to the embryo itself that leads to lethality at any stage of gestation right up to birth. Historically, much research has focused on the maternal endometrium, endocrine and immune responses in pregnancy and pregnancy loss, as well as infectious agents such as pathogens, and until recently very little was known about the both small and large genetic variants associated with reduced foetal viability in the horse. In this review, we first introduce key aspects of equine placental and foetal development. We then discuss incidence, risk factors and causes of pregnancy loss, with the latter focusing on genetic variants described to date that can impact equine foetal viability.

Simultaneous genome-wide haplotyping and copy number detection enables universal equine preimplantation genetic testing

“…The analysis of the TE biopsy could predict the euploid or aneuploid state of all embryos, highlighting its potential for PGT-A. Monosomies on small chromosomes, here detected in two embryos on chromosome 28 and 31, are associated with fetal demise by 65 days of gestation 11 . Therefore, clinical application and selection against such embryos could increase success rates per embryo transfer as well as the live-birth rates, as was shown for in vitro-produced cow embryos 30 .…”

“…Here, we demonstrate the presence of meiotic monosomies of larger chromosomes (e.g., chromosome 9 in Mare01_Embryo01 and chromosome 11 in Mare02_Embryo03) in arrested embryos but not in blastocysts. Together, these data suggest that monosomies of the larger chromosomes affecting all embryonic cells likely cause gene-dosage imbalances resulting in embryo arrest before embryonic genome activation and thus, pregnancy loss before clinical pregnancy detection 11 . We further provide the rst solid evidence of the occurrence of genome-wide errors in equine embryos.…”

“…These ndings corroborate the human observation that especially genomic aberrations that affect a large part of the genome in a large proportion of the embryo, such as (complex) aneuploidy resulting from mitotic errors at the earliest embryonic divisions, combinations of meiotic and mitotic aneuploidies, or ploidy aberrations seem detrimental to embryonic development while meiotic errors or low-grade mosaicism do not necessarily prohibit embryo development to the blastocyst stage 24,28,32,33,66,67 . In horses, meiotic monosomies of smaller autosomal chromosomes have been reported in aborted equine specimens (e.g., chromosome 26, 27 and 31), but never in live born horses 11,20 . Here, we demonstrate the presence of meiotic monosomies of larger chromosomes (e.g., chromosome 9 in Mare01_Embryo01 and chromosome 11 in Mare02_Embryo03) in arrested embryos but not in blastocysts.…”

“…Moreover, only 76-83% of the arti cial inseminations with fresh semen 6,7 and ~ 85% of fresh in vivo and ~ 70% of frozen-thawed day 6-9 in vitro-produced embryo transfers 3,[8][9][10] generate a clinical pregnancy. When a pregnancy is clinically detected after in vivo fertilization, 5-10% of day 14-and 5 to 10% of day 70-pregnancies additionally fail to produce a viable foal ( (reviewed elsewhere 11 ). Following IVEP, a doubled incidence of early pregnancy losses 9 , of which a higher rate seems to present as anembryonic vesicles 12,13 has been reported.…”

Overview of the causes of abortion in horses, their follow‐up and management

“…Recently, specific genetic variants have been linked to lethal congenital abnormalities. (Shilton et al, 2022).…”