Research Article: In vivo Multiphoton Microscopy Technique to Reveal the Physiology of the Mouse Placenta

Date Published: September 24, 2012

Publisher: Blackwell Publishing Ltd

Author(s): Ana C Zenclussen, David N Olivieri, Michael L Dustin, Carlos E Tadokoro.


Pregnancy is a challenge to the maternal immune system as it must defend the body against pathogens while at the same time develop immune tolerance against the fetus growing inside the uterus. Despite ex vivo techniques being used to understand these processes, in vivo techniques are missing.

To directly study these phenomena, we have developed a new microscope stage and surgical procedures for use in two-photon microscopy, for in vivo observation of the mouse placenta.

These tools and surgical procedures demonstrate fetal and maternal blood flow inside the labyrinth zone of the placenta, as well as its three dimensional structure. It was also useful to identify Plasmodium chabaudi-infected red blood cells inside this labyrinth zone.

We believe this technique will represent an important contribution for expanding the available knowledge concerning cell dynamics and interactions at the fetal-maternal interface.

Partial Text

The immune system evolved to maintain the integrity and function of host tissues. It is composed of different types of cells, each exerting specialized functions at different levels and operating under tight regulation.1 When this regulation breaks down, the function of targeted organs can fail leading to system-wide collapse.2 As an example, an imbalanced immune response that targets the reproductive system could lead to a miscarriage or impaired fetal development.3 Such events, if widespread, could obviously compromise the future of the entire species.

Mammalian evolution may have been greatly influenced by the uterus’ viviparous capacity and the existence of an intrauterine structure for embryo nurturing during development. This may be particularly true as both uterine and placental Metatheria (marsupials) and Eutheria (other mammals) animals outnumber the species of Prototheria animals, represented today only by platypus and echidnas. Moreover, many maternal physiologic systems and structures, as well as the immune system, have adapted to pregnancy. The immune system evolved to allow the growth of a semi-allogeneic tissue represented by the embryo through the active generation of tolerogenic processes; these mechanisms include the development of cells with the specific capacity to suppress the immune system such as regulatory T cells (Tregs). This is particularly fascinating, considering that the maternal immune system tolerates and fosters the growth and well-being of the growing fetus, while at the same time protecting the mother from infections. Nonetheless, this finely regulated balance can be compromised in the case of acute infections, leading possibly to premature pregnancy termination or fetal loss.




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