Yolk sac development, function and role in rodent pregnancy

Abstract

During the early phases of embryonic development, the yolk sac serves as an initial placenta in many animal species. While in some, this role subsides around the end of active organogenesis, it continues to have important functions in rodents, alongside the chorio‐allantoic placenta. The yolk sac is the initial site of hematopoiesis in many animal species including primates. Cells of epiblastic origin form blood islands that are the forerunners of hematopoietic cells and of the primitive endothelial cells that form the vitelline circulation. The yolk sac is also a major route of embryonic and fetal nutrition apparently as long as it functions. In mammals and especially rodents, macro and micronutrients are absorbed by active pinocytosis into the visceral yolk sac, degraded and the degradation products (i.e., amino acids) are then transferred to the embryo. Interference with the yolk sac function may directly reflect on embryonic growth and development, inducing congenital malformations or in extreme damage, causing embryonic and fetal death. In rodents, many agents were found to damage the yolk sac (i.e., anti–yolk sac antibodies or toxic substances interfering with yolk sac pinocytosis) subsequently affecting the embryo/fetus. Often, the damage to the yolk sac is transient while embryonic damage persists. In humans, decreased yolk sac diameter was associated with diabetic pregnancies and increased diameter was associated with pregnancy loss. In addition, culture of rat yolk sacs in serum obtained from pregnant diabetic women or from women with autoimmune diseases induced severe damage to the visceral yolk sac epithelium and embryonic malformations. It can be concluded that as a result of the crucial role of the yolk sac in the well‐being of the early embryo, any damage to its normal function may severely and irreversibly affect further development of the embryo/fetus.

Impaired yolk sac NAD metabolism disrupts murine embryogenesis with relevance to human birth defects

“…The yolk sac has a nutritional role in mammals as it uptakes and processes maternally derived macro- and micronutrients and transfers these to the embryo via their interconnected and expanding vasculature (Burton et al, 2016, Ornoy and Miller, 2023). In mice, histotrophic nutrition via the yolk sac is solely responsible for supporting the nutritional requirements of the developing embryo until the gradual transition to haemotrophic nutrition across the chorioallantoic placenta between E10 and 12 (Elmore et al, 2022).…”

“…Furthermore, the yolk sac metabolises teratogenic substances (Terlouw and Bechter, 1992). Disruption of yolk sac function causes embryonic malformation phenotypes that overlap with CNDD (Brent and Fawcett, 1998, Brent et al, 1971, Ornoy and Miller, 2023, Perez-Garcia et al, 2018), underscoring the yolk sac’s crucial role for normal embryo development.…”

Role of microglia in brain development after viral infection

“…Microglia solely originate from erythro-myeloid progenitors located in the embryonic YS, an extra-embryonic membrane tissue that serves as the first site of hematopoiesis in both rodents and humans ( Palis and Yoder, 2001 ; Colonna and Butovsky, 2017 ; Ornoy and Miller, 2023 ). In mice, the YS-derived microglial progenitors appear at embryonic day 7 (E7) to E8 and migrate to the brain as early as E9.5, following the establishment of blood vessels from the YS to the embryonic brain ( McGrath et al, 2003 ; Ginhoux et al, 2010 ; Ginhoux and Prinz, 2015 ).…”

The Yolk Sac’s Essential Role in Embryonic Development

“…There are excellent original papers and reviews on the development and structure of the mammalian yolk sac [4,25,26,27,28,29,30]. We summarize critical points based on these papers below.…”

“…2). In these animals, the yolk sac parallels the chorioallantoic placenta, absorbing nutrients from the mothers' uterus during pregnancy, digesting them, and transporting them to the fetus [29,30]. Another essential function is the transport of immunoglobulins to the fetus [28,29].…”