Placental development during early pregnancy in sheep: effects of embryo origin on vascularization

Abstract

Utero-placental growth and vascular development are critical for pregnancy establishment that may be altered by various factors including assisted reproductive technologies (ART), nutrition, or others, leading to compromised pregnancy. We hypothesized that placental vascularization and expression of angiogenic factors are altered early in pregnancies after transfer of embryos created using selected ART methods. Pregnancies were achieved through natural mating (NAT), or transfer of embryos from natural mating (NAT-ET), or in vitro fertilization (IVF) or activation (IVA). Placental tissues were collected on day 22 of pregnancy. In maternal caruncles (CAR), vascular cell proliferation was less (P<0.05) for IVA than other groups. Compared to NAT, density of blood vessels was less (P<0.05) for IVF and IVA in fetal membranes (FM), and for NAT-ET, IVF and IVA in CAR. In FM, mRNA expression was decreased (P<0.01–0.08) in NAT-ET, IVF and IVA compared to NAT for vascular endothelial growth factor (VEGF) and its receptor FLT-1, placental growth factor (PGF), neuropilin (NP) 1 and 2, angiopoietin (ANGPT) 1 and 2, endothelial nitric oxide synthase (NOS3), hypoxia inducible factor-1A (HIF1A), fibroblast growth factor (FGF) 2 and its receptor FGFR2. In CAR, mRNA expression was decreased (P<0.01–0.05) in NAT-ET, IVF and IVA compared to NAT for VEGF, FLT-1, PGF, ANGPT1 and TEK. Decreased mRNA expression for 12 of 14 angiogenic factors across FM and CAR in NAT-ET, IVF and IVA pregnancies was associated with reduced placental vascular development, which would lead to poor placental function and compromised fetal and placental growth and development.

Progesterone promotes fetal growth in a restricted interspecies gestation (Ovis canadensis x Ovis aries)

“…65 Higher levels of progesterone during all of gestation allow the mobilization of larger quantities of fatty acids and glucose from reserves into the maternal circulation, and similarly, greater development of the placenta produces greater placental lactogen and other hormones with mitogenic activity favouring the intrauterine growth of the foetus. 51,66 When comparing placental development in the second experiment of this work, it becomes noticeable that placentas from O. c. mexicana × O. aries interspecies gestations treated with progesterone have greater lengths, similar to that of intraspecies O. aries × O. aries gestations from the first experiment. This result could explain why the birth weight of hybrid offspring from the group treated with progesterone was also higher in relation to the hybrid offspring weight of the non treated control group.…”

Blastocyst transfer in mice alters the placental transcriptome and growth

“…These transcriptional changes might promote branching of additional villi and/or increased vascular density of existing villi (Wu et al 2003) to improve the surface area for exchange. In support of this hypothesis, increased placental vascular density is apparent after IVF (together with embryo transfer) in bovine and ovine conceptuses (Miles et al 2005, Grazul-Bilska et al 2014. IVF followed by blastocyst transfer in mice might lead to increased branching morphogenesis since an initially small placenta at E12.5 develops into a large placenta by late gestation (Delle Piane et al 2010, Bloise et al 2012.…”

Long term effects of ART: What do animals tell us?

“…In the early stages of gestation, at the time of implantation, both reduced and increased fetal growth have been reported in association with ART (Bertolini et al, ; Farin, Piedrahita, & Farin, ). Since the uterus responds and adapts to the origin of the embryo in ruminants (Grazul‐Bilska et al, ; Mansouri‐Attia et al, ), endometrial response to the IVP embryo has been studied together with placental response.…”