human pregnancy: placental studies (Introduction)

by David Turell , Tuesday, January 23, 2024, 18:45 (99 days ago) @ David Turell

Still not a well understood organ:

https://www.the-scientist.com/features/the-ephemeral-life-of-the-placenta-71516?utm_cam...

"Following fertilization, one cell becomes two, and those become four and so on, until the zygote transforms into a blastocyst around six days post fertilization (dpf).4 The blastocyst, or the preimplantation embryo, comprises of an inner cell mass (ICM) swaddled by an outer layer of cells that make up the trophectoderm. The trophectoderm, which is home to nearly 90 percent of the blastocyst cells, develops into the placenta while the ICM gives rise to the fetus.

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"Around six to seven dpf, the blastocyst implants into the surface of the uterine wall and begins its expansion.4 This area of the endometrium is transformed early on in pregnancy and acts as a fluffy bed in which the embryo grows. As the blastocyst burrows, the trophectoderm begins to differentiate into subtypes of trophoblast cells, starting with cytotrophoblasts, which are progenitor stem cells in the placenta that give rise to other trophoblasts.

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"As the invasion into the uterine wall wages on, cytotrophoblasts differentiate into syncytiotrophoblasts (SCT), which carve out villi, or frond-like structures that soon house the fetal capillary system.7 As SCT build larger and larger villi, cytotrophoblasts march forward to conquer a new frontier in search of nutrients to fuel the continued expansion. These rogue cytotrophoblasts go deeper into the uterine wall and differentiate into incredibly invasive extravillous trophoblasts (EVT). Once there, EVT hunt down uterine arteries, enlarge them, and hook them up to the placenta. Finally, around 10 weeks into the pregnancy, the parental circulation reaches the intervillous space.9 By 12 weeks, the placental blueprint is in place.

"The uterine wall is home to glands, vessels, stromal cells, and immune cells that interact with the invading fetal cells to create a boundary between the parent and fetus.4 The relationship between the parent and the growing fetus is often portrayed as parasitic or antagonistic, a 9-month war waged from within. This is due in part to the highly invasive nature of EVT leaching nutrients, but also the presence of the fetus’ foreign DNA. But Ashley Moffett, a reproductive immunologist at the University of Cambridge, said that the relationship between the parent and the placenta isn’t simply friend or foe. “It’s a compromise, actually.”

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"Uterine NK [natural killer] cells, which differ substantially from blood NK cells, dominate the immune cell landscape of the uterine wall bordering first trimester placentas. Moffett and others went on to characterize this unique immune cell and demonstrate its importance as a mediator between the needs of the mother to retain resources and the needs of the baby to grow.

"To explore the boundary between the parent and fetus, Moffett and her team used single-cell RNA sequencing on placental and endometrial samples donated by patients who underwent elective pregnancy termination in the first trimester.11 They identified transcription factors that orchestrate cytotrophoblast differentiation into SCT or EVT but also uncovered three subtypes of NK cells with distinct immune regulation and cell-cell communication profiles. Their findings further highlighted the compromise between parent and fetus, suggesting that NK cells keep a check on EVT expansion while these cells protect the fetus from parental immune responses.

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"As the pregnancy progresses, cytotrophoblast cells keep dividing, and the placenta keeps getting bigger and bigger to keep up with the needs of the growing fetus.

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"Following the birth of the baby comes the birth of the placenta as it sheds away from the lining of the uterus. By the end of gestation, the SCT region is incredibly invaginated and convoluted to provide a large surface area for diffusion to the baby. “If you were to spread it out it would be 13 square meters in size,” said Fogarty. That’s about the size of a parking space.

"Just like that, this transient organ that helped the fetus survive in the womb for the last nine months is gone. Scientists are increasingly appreciating the link between the in utero environment, including placental health, and susceptibility to chronic diseases later in life.

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“'Just over half of all pregnancies are uncomplicated, normal pregnancies,” said Fogarty. The other half are affected by miscarriage, intrauterine growth restriction, fetal growth restriction, and preeclampsia. “If we can make these insights, there’s going to be massive numbers of patients who can potentially be helped in the future. There’s potential to make a big impact.'”

Comment: This did not develop by chance.