human pregnancy strange progesterone activity (Introduction)
by David Turell 
, Tuesday, April 21, 2020, 21:58 (1675 days ago)
Our upright posture requires a different flatter broader shape to the pelvis than found in other primates. Our babies have bigger heads requiring larger pelvic openings, and the birth canal is tortuous, requiring a 90 degree turn and a 180 degree spin. In all other primates it is a direct shot. Squeeze hard and spit it out. Now it is found our progesterone levels and activities are very different:
https://medicalxpress.com/news/2020-04-human-pregnancy-weirdnew-mystery.html
"From an evolutionary perspective, human pregnancy is quite strange, says University at Buffalo biologist Vincent Lynch.
"'or example, we don't know why human women go into labor," Lynch says. "Human pregnancy tends to last longer than pregnancy in other mammals if you adjust for factors like body size. The actual process of labor tends to last longer than in other animals. And human pregnancy and labor are also much more dangerous."
"Past research has shown that the progesterone receptor gene underwent rapid evolution in humans, and some scientists have suggested that these swift changes occurred because they improved the function of the gene. This is called positive selection.
"But Lynch and Marinic's study—published online on April 17 in the journal PLOS Genetics—draws a different conclusion.
"Their research finds that while the progesterone receptor gene evolved rapidly in humans, there's no evidence to support the idea that this happened because those changes were advantageous. In fact, the evolutionary force of selection was so weak that the gene accumulated many harmful mutations as it evolved in humans, Lynch says. (my bold)
"The results come from an analysis of the DNA of 115 mammalian species. These included a variety of primates, ranging from modern humans and extinct Neanderthals to monkeys, lemurs and lorises, along with non-primate mammalian species such as elephants, pandas, leopards, hippos, aardvarks, manatees and walruses.
T"he findings were a surprise, Lynch says.
"'I thought that the progesterone receptor gene would have evolved to respond better to progesterone, to be better at suppressing inflammation or contractions to keep us pregnant for longer. It looks like it's the reverse: In human pregnancy, there's just an incredible amount of progesterone around, and yet the gene is less good at doing its job. I wonder if this might predispose us to things like preterm birth, which is not that common in other animals."
***
"During human pregnancy, these receptors detect the presence of progesterone, an anti-inflammatory hormone that pregnant women and the placenta produce at various points in time. When progesterone is present, the receptors jump into action, triggering processes that help keep women pregnant in part by preventing the uterus from contracting, reducing uterine inflammation, and suppressing the maternal immune response to the fetus, Lynch says.
"In addition to exploring the evolutionary history of the progesterone receptor gene, Lynch and Marinic conducted experiments to test whether mutations in the human version of the gene altered its function. The answer is yes.
"As the scientists wrote in their paper, "We resurrected ancestral forms of the progesterone receptor and tested their ability to regulate a target gene. We found that the human progesterone receptor forms have changed in function, suggesting the actions regulated by progesterone may also be different in humans. Our results suggest caution in attempting to apply findings from animal models to progesterone biology of humans.'"
Comment: Note my bold. We are very different. These Darwinists should accept that and accept the differences.
human pregnancy: placental processes
by David Turell , Thursday, July 06, 2023, 18:36 (504 days ago) @ David Turell
First trimester specimens examined:
https://www.nature.com/articles/s41586-023-05869-0
"Abstract:
The relationship between the human placenta—the extraembryonic organ made by the fetus, and the decidua—the mucosal layer of the uterus, is essential to nurture and protect the fetus during pregnancy. Extravillous trophoblast cells (EVTs) derived from placental villi infiltrate the decidua, transforming the maternal arteries into high-conductance vessels1. Defects in trophoblast invasion and arterial transformation established during early pregnancy underlie common pregnancy disorders such as pre-eclampsia2. Here we have generated a spatially resolved multiomics single-cell atlas of the entire human maternal–fetal interface including the myometrium, which enables us to resolve the full trajectory of trophoblast differentiation. We have used this cellular map to infer the possible transcription factors mediating EVT invasion and show that they are preserved in in vitro models of EVT differentiation from primary trophoblast organoids3,4 and trophoblast stem cells5. We define the transcriptomes of the final cell states of trophoblast invasion: placental bed giant cells (fused multinucleated EVTs) and endovascular EVTs (which form plugs inside the maternal arteries). We predict the cell–cell communication events contributing to trophoblast invasion and placental bed giant cell formation, and model the dual role of interstitial EVTs and endovascular EVTs in mediating arterial transformation during early pregnancy. Together, our data provide a comprehensive analysis of postimplantation trophoblast differentiation that can be used to inform the design of experimental models of the human placenta in early pregnancy.
***
"Discussion:
Our systems biology approach has enabled us to explore potential interactions between EVTs and maternal decidual cells. First, we predict the ligand–receptor interactions between the maternal macrophages and EVT, in keeping with the importance of decidual innate immune cells for placentation32. We further explore the poorly described macrophage–EVT signalling axis in vitro and describe upregulation of motility genes in the EVT subsets. Second, we pinpoint the potential molecular and cellular mediators of arterial transformation during early pregnancy. Interactions between PV1-AOC3 and iEVT could drive iEVT tropism towards the arterial wall and mediate the destruction of arterial smooth muscle media. eEVTs have a specific ECM that could allow them to form the plug. There are also specific interactions with endothelial cells that enable eEVTs to adhere to them. These novel interactions add to our understanding of the communication between endothelial and eEVT cells. The effect of defective arterial transformation in the later stages of pregnancy is well-described and underpins the great obstetric syndromes9. Our study increases the understanding of these major pregnancy disorders, all of which have their origins in the first trimester. In addition, our roadmap of trophoblast differentiation can be used as a blueprint to design improved in vitro models that fully recapitulate the early stages of implantation."
Comment: the content of this very advanced study is too complex to include here. Cell to cell automatic interactions control the implantation and its subsequent functions. Obviously designed.
human pregnancy: placental studies
by David Turell , Tuesday, January 23, 2024, 18:45 (303 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.
***
"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.
***
"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.”
***
"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.
***
"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.
***
"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.
***
“'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.
human pregnancy: retroviral role
by David Turell , Wednesday, January 24, 2024, 19:36 (302 days ago) @ David Turell
Ancient retroviral infections set up the current controls of embryo development:
https://phys.org/news/2024-01-virus-infected-animals-hundreds-millions.html
"All animals have evolved thanks to the fact that certain viruses infected primitive organisms hundreds of millions of years ago. Viral genetic material was integrated into the genome of the first multi-cellular beings and is still in our DNA today.
***
"...the role played by these viruses in a process that is absolutely vital for our development, and which occurs a few hours after fertilization: the transition to pluripotency, when the oocyte goes from having two to four cells.
"Before this step, each of the two cells of the embryo is totipotent, i.e. it may develop inside an independent organism; the four cells of the next stage are not totipotent but are pluripotent, because they can differentiate into cells of any specialized tissue of the body.
***
"Genetic material from the now so-called 'endogenous retroviruses' was integrated into the genomes of organisms that may have been drivers of the Cambrian explosion, a period more than 500 million years ago when the world's seas underwent a biodiversity 'boom.' Over the past decade, genetic sequences from these viruses have been found to make up at least 8–10% of the human genome.
"'Until recently, these viral remnants were considered to be 'junk DNA,' genetic material that was unusable or even harmful," explains De la Rosa. "Intuitively, it was thought that having viruses in the genome could not be good. However, in recent years we are starting to realize that these retroviruses, which have co-evolved with us over millions of years, have important functions, such as regulating other genes. It's an extremely active field of research."
"The research shows that the MERVL endogenous retrovirus sets the pace in embryo development, especially during the specific step of the transition from totipotency to pluripotency, and explains the mechanism that makes this happen.
"'It is a totally new role for endogenous retroviruses," says Djouder. "We discovered a new mechanism that explains how an endogenous retrovirus directly controls pluripotency factors."
"This new action mechanism involves URI, a gene that Djouder's group is researching in depth. Years ago, it was discovered that if URI is deleted in laboratory animals, embryos do not even get to develop. De la Rosa wanted to find out why, and which is how its link to the MERVL retrovirus was discovered.
"The findings show that one of the functions of URI is to enable the action of molecules essential for acquiring pluripotency; if URI does not act, neither do the pluripotency factors, and the cell remains in a state of totipotency. It turns out to be an endogenous retrovirus protein, MERVL-gag, which modulates the action of URI.
"The researchers found that during the totipotency phase, when there are only two cells in the oocyte, expression of the MERVL-gag viral protein is high; this protein binds to URI and prevents it from acting. However, the levels gradually change, so that the levels of MERVL-gag viral protein go down and URI can enter into action: pluripotency appears.
***
"'Our findings reveal symbiotic co-evolution of endogenous retroviruses with their host cells in order to guarantee the smooth and timely progression of early embryonic development," explain the authors.
"In other words, the three-way relationship between the viral protein, URI and pluripotency factors is finely modulated, "to allow sufficient time for the embryo to adjust and coordinate the smooth transition from totipotency to pluripotency and cell lineage specification during embryonic development," concludes Djouder."
Comment: this role of retroviruses shows us how vital viruses were in the development of the evolution of DNA. The answer to theodicy complaints is how important bacteria and vi ruses are to life in general.
human pregnancy: roles of various organs
by David Turell , Thursday, February 01, 2024, 20:53 (294 days ago) @ David Turell
Various metabolitic relationships explored:
https://www.newscientist.com/article/2415377-we-now-have-a-map-of-how-pregnancy-changes...
"Outside of pregnancy, different bodily systems usually “feed” each other molecular nutrients, known as metabolites, in a relatively even exchange.
"But tissues throughout the body undergo significant changes during pregnancy. For instance, the heart increases its pumping volume by up to 40 per cent. But the thymus, involved in the immune system, “shrinks away really fast” to prevent rejection of the fetus, says Shyh-Chang Ng at the Chinese Academy of Sciences in Beijing.
***
"The researchers analysed the samples for metabolites, comparing each site during the non-pregnant state with its equivalent during the three trimesters.
"As expected, when the macaques weren’t pregnant, their metabolites were shared fairly evenly across parts of the body, says Ng. But to his surprise, pregnancy resulted in the exchange getting “reprogrammed dramatically”.
In the first trimester, for example, the uterus decreased its exchanges with the heart and skeletal muscles, “coupling” instead with the developing placenta. During the second trimester, the fully formed placenta started sending out “a whole host of metabolites” to the heart, ovaries and liver, while the uterus gradually shifted towards coupling with the scalp by the third trimester.
"Also in late pregnancy, the skeletal muscles had significant exchanges with the spinal cord. The researchers didn’t investigate why any of these coupling changes occur.
***
"In another experiment, the researchers took blood serum samples from 32 pregnant women, finding a “huge drop” in levels of the metabolite corticosterone among those with pre-eclampsia, says Ng. They then deprived human placenta cells of corticosterone in the laboratory, which resulted in pre-eclampsia-like inflammation. “Corticosterone is a key steroid in human pregnancy,” says Ng. “It’s been underappreciated.”
"A second key metabolite appears to be palmitoylcarnitine, which helps process fatty acids and regulate immunity. An ongoing human stem cell study led by Ng suggests it might play a role in gestational diabetes, he says.
***
"Previous studies have investigated metabolic changes in pregnant rats and mice, but crab-eating macaques have a far more human-like reproductive system, says Ng. Despite having shorter pregnancies than people – averaging about 26 weeks versus 40 weeks – the macaques still serve as reliable models for human reproduction, particularly for pregnancy-related conditions, he says."
Comment: all of these alterations are controlled from the pituitary, and feedback loops control the new levels. A wonderful example of how the body integrates.