Defining the male contribution to embryo quality and offspring health in assisted reproduction in farm animals

Abstract

Assisted reproductive technologies such as artificial insemination have delivered significant benefits for farm animal reproduction. However, as with humans, assisted reproduction in livestock requires the manipulation of the gametes and preimplantation embryo. The significance of this 'periconception' period is that it represents the transition from parental genome regulation to that of the newly formed embryo. Environmental perturbations during these early developmental stages can result in persistent changes in embryonic gene expression, fetal organ development and ultimately the long-term health of the offspring. While associations between maternal health and offspring wellbeing are well-defined, the significance of paternal health for the quality of his semen and the post-conception development of his offspring have largely been overlooked. Human and animal model studies have identified sperm epigenetic status (DNA methylation levels, histone modifications and RNA profiles) and seminal plasma-mediated maternal uterine immunological, inflammatory and vascular responses as the two central mechanisms capable of linking paternal health and post-fertilisation development. However, there is a significant knowledge gap about the father's contribution to the long-term health of his offspring, especially with regard to farm animals. Such insights are essential to ensure the safety of widely used assisted reproductive practices and to gain better understanding of the role of paternal health for the well-being of his offspring. In this article, we will outline the impact of male health on semen quality (both sperm and seminal plasma), reproductive fitness and post-fertilisation offspring development and explore the mechanisms underlying the paternal programming of offspring health in farm animals.

Seminal Plasma: Relevant for Fertility?

“…One could state that this is what has been proven when IVF was established, putting most weight on spermatozoa, which included the removal of the native SP. IVF and intracytoplasmic sperm injection (ICSI) of ejaculated or epididymal spermatozoa, or even elongated spermatids that have never gone through sperm maturation, has resulted in fertilization, embryo development, pregnancies and births in humans [ 202 ] and animals [ 203 ], implying that the SP is not a mandatory component. However, human fertility (as baby births) after embryo transfer of IVF/ICSI “fertilized” oocytes has been steady around 30% since 1994, in general terms [ 204 ].…”

Programming of Embryonic Development

“…Authors reviewing 45 publications reporting data from rodent models presented overwhelming evidence that developmental programming extends to the F2 generation and beyond, with several of the papers reviewed presenting evidence of a paternal contribution to developmental programming [98]. Paternal diet has been shown to affect growth, metabolism, and reproductive traits in the offspring of rodents and sheep, potentially across multiple generations [12,14,[17][18][19][20][21]. Messages carried in a father's semen after exposure to alcohol, drugs, or an obese state result in altered development of their children [99,100].…”

“…Both assisted reproductive techniques (ART; e.g., embryo transfer [ET], in vitro fertilization [IVF], in vitro production of embryos [IVP], and cloning), and maternal nutritional 2 of 15 status (e.g., over-or underfeeding or feeding specific nutrients) have profound effects on embryonic development during the periconceptual period (i.e., around the time of fertilization/conception) and continuing into early pregnancy, which is the period of embryonic/fetal organogenesis and placentation [1,5,6,[9][10][11]. As discussed in several recent reviews [12][13][14], paternal nutritional status, via effects on sperm gene expression and epigenetic landscape, extracellular vesicles, and seminal plasma content, has been shown to contribute to embryo quality and affect embryonic/fetal and placental development in cattle [15,16], rodents [17][18][19][20], and sheep [21,22] models.…”

“…Some of the programming effects of ART and periconceptual parental nutrition likely depend on the epigenetic profile the oocyte or the sperm. The oocyte [10] and sperm [14,15,17,22,[45][46][47][48][49][50][51] both contribute mRNAs, small non-coding RNAs, and proteins to the embryo, and these have profound influences on embryonic development before activation of the embryonic genome [10,[52][53][54]. In addition, both the maternal (oocyte) and paternal (sperm) genomes can "transfer" their DNA methylation status to the embryo, and this is influenced by ART and nutritional status [10,15].…”

Significance and Relevance of Spermatozoal RNAs to Male Fertility in Livestock

“…Seminal plasma components have no role in assisted reproductive technologies (ART) and, therefore, are excluded from IVF and intracytoplasmic injection (ICSI) of ejaculated sperm. The ARTs have resulted in successful fertilization, pregnancy, and live birth of offspring in humans ( Marzano et al, 2020 ) and animals ( Morgan et al, 2020 ) without the use of seminal plasma. However, recent studies have found that the spRNA population may be contributed by seminal plasma via exosome.…”