Human development - the first 13 days

Human embryo Carnegie Stage 5c (Carnegie Embryo #7700)
Photomicrograph courtesy of Dr. Allen C. Enders

A system created for cultivating mouse blastocysts has been applied successfully to describe the development of the human embryo for 13 days after in vitro fertilization. This is a step towards opening the black box in our understanding of human embryology (reviewed here). Hitherto we have been confined to interpreting the histological sections of embryos in the Carnegie Collection.

Papers by two groups were just published: Shahbazi et al. in Nature Cell Biology and Deglincerti et al. in Nature. They used appropriate molecular markers to identify epiblast, primitive endoderm (hypoblast) and trophectoderm. In addition they used cytokeratin 7 and human chorionic gonadotrophin as markers for cyto- and syncytiotrophoblast.


Day 13 embryo of the rhesus macaque (Macaca mulatta)
Courtesy of Dr. Allen C. Enders

Both groups showed the appearance of cavities corresponding to the amnion and primary yolk sac as known from studies in the rhesus macaque by Enders, Schlafke and Hendrickx. In the macaque, the yolk sac (at bottom in the figure) is outlined by visceral endoderm (beneath the epiblast) and the more squamous parietal endoderm. These tissues were identified by Shahbazi et al. in human embryos and shown to express the endoderm marker GATA6.  Deglincerti et al. found the GATA6 signal was low in the parietal cells and that they expressed the trophectoderm marker CDX2. This is an interesting observation but hardly justifies them calling these cells "yolk sac trophectoderm." The term was criticized by Janet Rossant in the accompanying News and Views (here)  and it must be hoped it does not gain currency.

As in the macaque, amnion formation was by cavitation. This is nicely described by Shahbazi et al. Unfortunately they use the term pro-amnion, which is appropriate in the mouse but not in primates (contrasted here).

Differentiation of trophectoderm into cytotrophoblast and multinucleated syncytiotrophoblast was confirmed with appearance of lacunae in the latter as appropriate for Carnegie Stage 5c.

Placentation in the Tasmanian bettong

Tasmanian bettong (Bettongia gaimardi cuniculus)
By JJ Harrison (CC BY-SA 3.0) via Wikimedia Commons
 

Now regarded as a subspecies of Eastern bettong (the mainland subspecies is extinct), the fetal membranes of this small kangaroo were described in 1930 by Theodore Thomson Flynn.

Trilaminar omphalopleure (vascular yolk sac) of Tasmanian bettong
From Flynn Proc Linn Soc NSW 1930; 55: 506-531

The yolk sac comprises a vascular portion (trilaminar omphalopleure) and a non-vascular portion (bilaminar omphalopleure). The sketch above shows trophoblast of the vascular yolk sac (troph) absorbing secretions from a uterine gland (gl ep). It is unclear whether there is exchange between the capillaries on the maternal (m cap) and fetal (foet cap) sides.

Bilaminar omphalopleure (non-vascular yolk sac) of Tasmanian bettongFrom Flynn Proc Linn Soc NSW 1930; 55: 506-531

Trophoblast of the non-vascular yolk sac (bilaminar omphalopleure) was implicated in the uptake of cellular material (cm) and red blood cells (haem). In current terminology (here) it is heterophagous.

Theodore Thomson Flynn (right) with his son the actor Errol Flynn

Theodore Thomson Flynn was a marine biologist and professor at the University of Tasmania. He named a fish Gibbonsia erroli after his son Errol Flynn the film actor.

Placentation in opossums

Embryo of Virginia Opossum (Didelphys virginiana) at 6 days
of gestation. Opened to show the vessels of the trilaminar yolk sac
and free-floating allantoic sac. From Selenka 1886.

Emil Selenka did not confine himself to rodents and primates (previous post and recent review). He also gave the first detailed description of embryonic development in a marsupial, the Virginia opossum. He bred them in the laboratory and thus had dated pregnancies.

All marsupials have a yolk sac placenta with both two-layered and three-layered areas (bilaminar and trilaminar omphalopleure); the latter has blood vessels that radiate from a sinus terminalis as can be seen in Selenka's illustration.



Neonate of Virginia Opossum. From Selenka 1886.

The Virginia opossum has a pretty short gestation even for a marsupial. The neonate above was born after 13 days. Development is supported largely by histotrophic nutrition, i.e. uptake of uterine gland secretions. The vascular part of the yolk sac is thought to be more important for gaseous exchange.

Note that the allantois makes no contact with the trophoblast. Unlike in the koala, wombat and bandicoots, there is nothing approaching chorioallantoic placentation. The allantois serves mainly as a receptacle for urine excreted by the mesonephros (here). 

Virginia Opossum (D. virginiana) by Cody Pope CC BY-SA 2.5
(Wikipedia Commons)
 

There are 87 species of didelphids in Central and South America, but the Virginia opossum is alone in extending its range to the USA and Canada.

Despite the species richness, placentation has been described for only five opossums; three from the same genus (D. virginiana, D. aurita and D. marsupialis) plus the gray short-tailed opossum (Monodelphis domestica) and gray four-eyed opossum (Philander opossum). I will save them for a later post.

The mouse yolk sac

Placenta Volume 36 Issue 10 October 2015

Great to see yolk sacs on the front cover of Placenta. Too often the mouse yolk sac is discarded or ignored in the laboratory - either through ignorance or because it has no obvious equivalent in human pregnancy. This particular study showed how mouse deficient in the OGA gene have defective blood vessel formation (vasculogenesis). This affected branching of the blood vessels in the yolk sac.

Ignorance of the yolk sac is evidenced by a high impact journal publishing a schematic where mouse yolk sac is shown to be only residual as occurs in humans (here).

I believe the mouse model of placentation is incomplete unless the yolk sac is studied along with the chorioallantoic placenta (argued here).