Pregnancy Foetus Mother Essay

Pregnancy is a state whereby there is a symbiotic union between a mother and her foetus. During this period, all systems of the body change to accommodate the trophoblast, the immune system (a complex biological signalling system responsible for protecting us against infection, disease and foreign objects due to its ability to differentiate between self and non self) being one of these systems also undergoes a number of changes (Markert, 2005). The foetus is like a homograft attached to the uterine wall of the mother via the placenta, it inherits half its genetic makeup from its mother and the other half from its father. Pregnancy Foetus Mother Essay. The paternal genes that it expresses are seen as antigens by the mothers immune system and are expected to cause the rejection of the foetus as a semi-allogenic tissue graft(2). Instead, the mothers’ immune system teaches itself to tolerate these genes and the development of the foetus is supported and regulated (Marker, 2005). The immunological puzzle that leads to the sustainment of the foetus for the 9 months gestation period is known as the “immunological paradox of pregnancy” (Claman. 1993).

A question that begets to be asked is how does the maternal body prevent rejection of the histoincompatible foetus and at the same time maintain enough maternal host defence mechanisms to fight disease and infection? To date it is not fully understood how this takes place, but it is known that in order to allow the foetus to escape rejection and immunological attacks by the maternal immune system, this symbiotic relationship must have distinctive immuno-regulatory actions. At the same time the mothers’ immune system must also provide protection against foreign antigens for her as well as her young.

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A number of explanations have been proposed during the last century as to why foetal rejection does not take place in healthy pregnancies. It is now agreed upon that the placenta plays an important role in this. The placenta is a very important organ because not only does it aid the transportation of nutrients and waste products and immunity between mother and foetus, it acts as an endocrine organ because it secretes growth factors and female hormones which helps maintain and support the pregnancy (Knobil and Neil, 1994) and finally the placental expression patterns of majorhistocompatibility complexes (MHC) is one of the vital factors that determine if a foetus is accepted or rejected, in humans these complexes are known as human leukocyte antigen (HLA) complexes (Claman. 1993). Although the mechanism for the maternal tolerance of the MHCs expressed by the fetus is still not fully known it is known that in humans, a number of HLA class I expressions have been detected in the placenta, these include HLA-C and HLA-G complexes. HLA-G is essential for the successful implantation of trophoblast and its protection from invasion. It does so by binding inhibitory receptors on T-lymphocytes and maternal uterine natural killer cells and thus protects the trophblast from maternal attacks caused by these cells. They also regulate cytokine secretion of cells, thus offering protection to the foetus (hla class 1 molecules reference). A recent study has also shown that HLA-G might inhibit the migration of NK cells across the placental endothelial cells. Till this day, no evidence has been brought forward to suggest that HLA-A, HLA-B and Class II MHCs are expressed in the placenta thus it is inferred that they are normally absent from the placenta during pregnancy (Bulmer and Johnson, 1985). Pregnancy Foetus Mother Essay.

Foetuses are protected not only from rejection during the gestation period but also from infections by the transmission of passive immunity from the mother.In 1892, Paul Erlich used mouse models to demonstrate that fetuses and neonates acquire protective immunity from their mothers both in utero and through breast milk. It has been shown that this involves the active transport of IgG from mother to her offspring. Passive immunity is transferred from the mother to her foetus through the placenta in the form of immunoglobulin G (IgG) and also via breast milk postnatally (Arvola et al 2000). IgG is the main defence against bacteria thus it accounts for 70-75% of antibodies found in human serum. Before birth the foetus is immunologically naïve because its synthesis of antibodies is very low. The immature immune system of the foetus is compensated for by the active transport of maternal IgG across the placenta into the foetal circulation. Before IgG reaches the foetal circulation, it has to cross two cellular barriers, the barrier in contact with the maternal blood known as the syncythiotrophoblast and the capillary epithelium of the foetus. IgG antibodies are conveyed across the placenta and the intestinal epithelium via the human Fc receptor (add more).

Although the ability of IgG to cross the placenta acts to convey passive immunity to the foetus there are instances where its ability to cross the placenta can have detrimental effects on the baby. An example of this is a condition called haemolytic disease of the new born (HDN). HDN is an alloimmune disease that develops in rhesus positive foetuses that have a rhesus negative mother. the mother produces IgG antibodies against the rhesus positive red blood cells which cross the placenta and attack red blood cells in the foetal circulation.

It has been established that breast milk are rich in maternal cells including small proportions of epithelial cells, macrophages, leukocytes and T and B lymphocytes which make up a majority of cells found in milk on the other hand, 80% of the total cells found in the colostrum (first milk secreted after delivery) are mononuclear phagocytes. Pregnancy Foetus Mother Essay. These cells aid the neonate by protecting the lumen of its gut and transferring immunity passively. Breast milk macrophages enter breast milk via the epithelium of the mammary gland, they are found to be highly phagocytic in breast milk and can easily be differentiated from other cells by the lipid rich inclusions found in their cytoplasm (breast milk macrophages reference). Milk and colostrum are also rich in the dimeric immunoglobin A. IgA antibodies are very important to the newborn because they are highly specific for pathogens found in the mucosae of the gut. This form of passive immunity from the mother thus conveys protection to the newborn until its immune response is mature enough to mount a good enough response (PDF2D).

As well as transference of immunity, a mother can also convey infections to her foetus. The maternal transmission of an infection such as HIV, Hepatitis B and syphilis to foetus in utero, as a result of body fluid transmission during child birth and through breast milk is known as vertical transmission. During pregnancy, the maternal transmission of infection can result in a number of sequela. Infections found in mother have the potential of infecting the foetus or newborn. Side effects of infections include abortion or stillbirth, acute illnesses, congenital abnormalities, neonatal death and many more. The newborn can acquire infections in utero also known as intrauterine (congenital), during child birth (intrapartum) or after birth (postpartum). Different forms of infections can be vertically transmitted, these include viral and bacterial infections which are both covered in this essay.

The most common examples of viral infections transferred from mother to her unborn child are cytomegalovirus, rubella both of which may cause severe neonatal disease or congenital defects, HIV and Hepatitis B.

The human immunodeficiency virus (HIV) is a sexually transmitted virus that attacks the immune system by infecting CD4 cells thus leaving the host vulnerable to other infections. This virus can lead to the acquired immunodeficiency syndrome which is characterised by a very low CD4 cell count (less than 200/ml). The transmission of this virus from mother to child can occur in utero, during child birth and via breast milk. The most common mode of transmission of HIV occurs during labour or at child birth, about 50-80% of vertical transmission occurs via this route. The reason being that the fetus is in direct contact with infected blood and secretions, as a result of ruptured membranes and transmission of maternal blood to the foetus during labour (birth by caesarean section before the beginning of labour and membrane rupture is proven to reduce this risk of transmission of HIV) (www.aafp.org).

HIV transmission can also occur in utero. The foetus can become infected if it comes in contact with infected maternal blood and secretions. This contact can be the result of placental haemorrhage or by the foetus swallowing some amniotic fluid (www. the-aids-pandemic.blogspot.com).

The final mechanism by which vertical transmission if HIV can take place is through breast milk which occurs in 16-29% of cases (www. the-aids-pandemic.blogspot.com). Pregnancy Foetus Mother Essay.

Hepatitis B is a viral infection of the liver caused by the hepatitis B virus (a double stranded DNA virus which caused liver damage). In 2004, Zhang et al provided evidence that the main route of transmission of hepatitis from mother to foetus was via the placenta. Mothers that have the acute form of the virus and that are also infected in the first trimester of pregnancy have a 10% chance of passing the virus to their neonates. This percentage increases to a staggering 80-90% if the mothers were infected in the 3^rd trimester. 90% of neonates on the other hand acquire the infection if the virus chronically infected the women (Hieber et al 1977).

Transmission is also caused by the exposure of the foetus to infected blood and body fluids. A hepatitis positive mother has a 20% chance of passing the infection to her offspring during child birth, this risk increases to 90% if the mother is also positive for the hepatitis B e antigen (www.perinatology.com). According to Hill et al (2002), breast milk of infected individuals contains HBV DNA, but using appropriate immunoprophylaxis nullifies the transmission of HBV.

Rubella (the German measles) is a condition caused by the rubella virus. This virus is moderately contagious. It can cross the placenta causing a condition known as congenital rubella syndrome (CRS) which leads to a number of side effects to the baby including low birth weight, deafness, mental retardation, congenital heart failure and death. The severity of the effect depends on the period that the fetus is infected; during the first two months of gestation the chances of foetal damage caused by infection is 65-0%, this chance decreases to 30-35% during the third month and finally to a mere 1-2% in the 20^th week.

There are two routes through which a newborn can acquire a bacterial infection, these routes include intraturerine (transplacental and assending infection) and intrapartum when the new born comes in contact with infected secretions and blood during delivery.

Congenital syphilis is a severe and life threatning multisystem infection caused by the vertical transmission of the spirochete Treponema palladium to the foetus. The transplacental transmission rate is 60-80% Vertical transmission of congenital syphilis can occur at anytime during pregnancy although the infection is more likely to be transmitted by women in the primary and secondary stages of the disease as opposed to the latent stage.Just like in adult syphilis, this infection is categorised into early disease which is seen in children two years or younger and late disease which is seen in children over the age of two(http://www.merck.com).

During child birth organisms such as N. gonorrhoea, B. streptococci and C. trachomonas bacteria that are naturally found in the female reproductive system can also colonise the newborn. A list of these bacteria are shown in fig 1 of the appendix attached.

Vertical transmission of Immunity during pregnancy is complex and one that intrigues many a soul. Pregnancy Foetus Mother Essay. Till this date its mechanisms are not fully known. What is known is that a number of complex systems are involved in the process and without the foetus will either be rejected or infected by pathogens.

hat sight could be more moving than a mother nursing her baby? What better icon could one find for love, intimacy and boundless giving? There’s a reason why the Madonna and Child became one of the world’s great religious symbols.

To see this spirit of maternal generosity carried to its logical extreme, consider Diaea ergandros, a species of Australian spider. All summer long, the mother fattens herself on insects so that when winter comes her little ones may suckle the blood from her leg joints. As they drink, she weakens, until the babies swarm over her, inject her with venom and devour her like any other prey.

You might suppose such ruthlessness to be unheard-of among mammalian children. You would be wrong. It isn’t that our babies are less ruthless than Diaea ergandros, but that our mothers are less generous. The mammal mother works hard to stop her children from taking more than she is willing to give. The children fight back with manipulation, blackmail and violence. Their ferocity is nowhere more evident than in the womb.

This fact sits uncomfortably with some enduring cultural ideas about motherhood. Even today, it is common to hear doctors talking about the uterine lining as the ‘optimal environment’ for nurturing the embryo. But physiology has long cast doubt on this romantic view.

The cells of the human endometrium are tightly aligned, creating a fortress-like wall around the inside of the uterus. That barrier is packed with lethal immune cells. As far back as 1903, researchers observed embryos ‘invading’ and ‘digesting’ their way into the uterine lining. In 1914, R W Johnstone described the implantation zone as ‘the fighting line where the conflict between the maternal cells and the invading trophoderm takes place’. It was a battlefield ‘strewn with… the dead on both sides’.

When scientists tried to gestate mice outside the womb, they expected the embryos to wither, deprived of the surface that had evolved to nurture them. To their shock they found instead that – implanted in the brain, testis or eye of a mouse – the embryo went wild. Placental cells rampaged through surrounding tissues, slaughtering everything in their path as they hunted for arteries to sate their thirst for nutrients. It’s no accident that many of the same genes active in embryonic development have been implicated in cancer. Pregnancy is a lot more like war than we might care to admit. Pregnancy Foetus Mother Essay.

So if it’s a fight, what started it? The original bone of contention is this: you and your nearest relatives are not genetically identical. In the nature of things, this means that you are in competition. And because you live in the same environment, your closest relations are actually your most immediate rivals.

It was Robert Trivers, in the 1970s, who first dared to explore the sinister implications of this reality in a series of influential papers. The following decade, a part-time graduate student named David Haig was musing over Trivers’s ideas when he realised that the nurturing behaviour of mammal mothers creates a particularly excellent opportunity for exploitation.

It is in your mother’s genetic interests, Haig understood, to provide equally for all her children. But your father might never have another child with her. This makes her other children your direct competitors, and also gives your father’s genes a reason to game the system. His genome would evolve to manipulate your mother into providing more resources for you. In turn, her genes would manoeuvre to provide you with fewer resources. The situation becomes a tug-of-war. Some genes fall silent, while others become more active, counterbalancing them.

Even with the help of modern medicine, pregnancy still kills about 800 women every day worldwide

That insight led Haig to found the theory of genomic imprinting, which explains how certain genes are expressed differently depending on whether they come from your father or your mother. Armed with this theory, we can see how conflicts of genetic interest between parents play out within the genomes of their offspring.

Because both parental genomes drive each other to keep ramping up their production of powerful hormones, should one gene fail, the result can be disastrous for both mother and infant.Pregnancy Foetus Mother Essay.  Normal development can proceed only as long as both parental genotypes are correctly balanced against one another. Just as in a tug-of-war, if one party drops its end, both fall over. This is one reason why mammals cannot reproduce asexually, and why cloning them is so difficult: mammalian development requires the intricate co-ordination of paternal and maternal genomes. A single misstep can ruin everything.

Diaea ergandros, the ultimate mother, doesn’t have to worry about this, of course. She will never have more than one brood, so there is no need for her to restrain her offspring. But most mammal mothers breed more than once, and often with different males. This fact alone ensures that the paternal and maternal genomes work against one another. You can see the tragic consequences of this hidden war throughout the class Mammalia. Yet there is one species where it ascends to really mind-boggling heights of bloodiness.

Yours.

For most mammals, despite the underlying conflict, life goes on almost as normal during pregnancy. They flee from predators, capture prey, build homes and defend territories – all while gestating. Even birth is pretty safe: they might grimace or sweat a bit during labour, but that’s usually the worst of it. There are exceptions. Hyena mothers, for example, give birth through an impractical penis-like structure, and about 18 per cent of them die during their first delivery. But even for them, pregnancy itself is rarely perilous.

If we look at primates, however, it’s a different story. Primate embryos can sometimes implant in the Fallopian tube instead of the womb. When that happens, they tunnel ferociously towards the richest nutrient source they can find; the result is often a bloodbath. And among the great apes, things look even dicier. Here we start to see perhaps the most sinister complication of pregnancy: preeclampsia, a mysterious condition characterised by high blood pressure and protein discharge in the urine. Preeclampsia is responsible for around 12 per cent of human maternal deaths worldwide. But it’s very much just the start of our problems.

The mother is a despot: she provides only what she chooses

A list of the reproductive ills that afflict our species might start with placental abruption, hyperemesis gravidarum, gestational diabetes, cholestasis and miscarriage, and carry on from there. In all, about 15 per cent of women suffer life-threatening complications during each pregnancy. Without medical assistance, more than 40 per cent of hunter-gatherer women never reach menopause. Even with the help of modern medicine, pregnancy still kills about 800 women every day worldwide. Pregnancy Foetus Mother Essay.

So, we have a bit of a mystery here. The basic genetic conflict that makes the womb such a battle zone crops up across innumerable species: all it takes for war to break out is for mothers to have multiple offspring by different fathers. But this is quite a common reproductive arrangement in nature, and as we saw, it doesn’t cause other mammals so many problems. How did we humans get so unlucky? And does it have anything to do with our other extraordinary feature – our unparalleled brain development?

In most mammals, the mother’s blood supply remains safely isolated from the foetus. It passes its nutrients to the foetus through a filter, which the mother controls. The mother is a despot: she provides only what she chooses, which makes her largely invulnerable to paternal manipulation during pregnancy.

In primates and mice, it’s a different story. Cells from the invading placenta digest their way through the endometrial surface, puncturing the mother’s arteries, swarming inside and remodelling them to suit the foetus. Outside of pregnancy, these arteries are tiny, twisty things spiralling through depths of the uterine wall. The invading placental cells paralyse the vessels so they cannot contract, then pump them full of growth hormones, widening them tenfold to capture more maternal blood. These foetal cells are so invasive that colonies of them often persist in the mother for the rest of her life, having migrated to her liver, brain and other organs. There’s something they rarely tell you about motherhood: it turns women into genetic chimeras.

Perhaps this enormous blood supply explains why primates have brains five to ten times larger than the average mammal. Metabolically speaking, brains are extremely expensive organs, and most of their growth occurs before birth. How else is the fetus to fund such extravagance?

Is this unfettered access to maternal blood the key to the extraordinary brain development we see in young primates?

Given the invasive nature of pregnancy, it’s perhaps not surprising that the primate womb has evolved to be wary of committing to it. Mammals whose placentae don’t breach the walls of the womb can simply abort or reabsorb unwanted foetuses at any stage of pregnancy. For primates, any such manoeuvre runs the risk of haemorrhage, as the placenta rips away from the mother’s enlarged and paralysed arterial system. And that, in a sentence, is why miscarriages are so dangerous.

It’s also why primates make every effort to test their embryos before they allow them to implant. The embryo is walled out by the tight-packed cells of the endometrium, while an intimate hormonal dialogue takes place. This conversation is, in Haig’s words, a ‘job interview’. Should the embryo fail to convince its mother that it is a perfectly normal, healthy individual, it will be summarily expelled.

How does an embryo convince its mother that it is healthy? By honestly displaying its vigour and lust for life, which is to say, by striving with all its strength to implant. And how does the mother test the embryo? By making the embryo’s task incredibly difficult. Just as the placenta has evolved to be aggressive and invasive, the endometrium has evolved to be tough and hostile. For humans, the result is that half of all human pregnancies fail, most at the implantation stage, so early that the mother may not even realise she was pregnant.

Embryonic development becomes a trial of strength. And this leads to another peculiarity of the primate reproductive system – menstruation. Pregnancy Foetus Mother Essay. We have it for the simple reason that it’s not such an easy matter to dispose of an embryo that is battling to survive. The tissues of the endometrium are partially insulated from the mother’s bloodstream, protecting her circulatory system from invasion by a placenta she has not yet decided to accept. But that means her own hormonal signals can struggle to be heard inside the womb. So, rather than risk corruption of the endometrial tissue and ongoing conflict with an embryo, what does the mother do? She just sloughs off the whole endometrium after each ovulation. This way, even the most aggressive embryo has to have her agreement before it can get comfortable. In the absence of continual, active hormonal signalling from a healthy embryo, the entire system auto-destructs. Around 30 per cent of pregnancies end this way.

I said that the mother struggles to pass hormonal signals into the womb. The thing is, once the embryo implants, it gets full access to her tissues. This asymmetry means two things. Firstly, the mother can no longer control the nutrient supply she offers the foetus – not without reducing the nutrient supply to her own tissues. Is this unfettered access to maternal blood the key to the extraordinary brain development we see in young primates? Fascinatingly, the intensity of the invasion does seem to correlate with brain development. Great apes, the largest-brained primates, seem to experience deeper and more extensive invasion of the maternal arteries than other primates. In humans – the largest-brained ape of all – placental cells invade the maternal bloodstream earlier even than in other great apes, allowing the foetus unprecedented access to oxygen and nutrients during early development. This would be one of evolution’s little ironies: after all, if it wasn’t for the cognitive and social capacities granted by our big brains, many more of us would die from the rigours of our brutal reproductive cycle. One can imagine how the two traits might have arisen in tandem. But the connection remains speculative. Uteri rarely fossilise, so the details of placental evolution are lost to us.

The second major consequence of the foetus’s direct access to maternal nutrients is that the foetus can also release its own hormones into the mother’s bloodstream, and thus manipulate her. And so it does. The mother counters with manipulations of her own, of course. But there is a strong imbalance: while the foetus freely injects its products into the mother’s blood, the mother is granted no such access to foetal circulation. She is walled out by placental membranes, and so her responses are limited to defensively regulating hormones within her own body. Pregnancy Foetus Mother Essay.

As the pregnancy continues, the foetus escalates its hormone production, sending signals designed to increase the mother’s blood sugar and blood pressure and thus its own resource supply. In particular, the foetus increases its production of a hormone that prompts the mother’s brain to release cortisol, the primary stress hormone. Cortisol suppresses her immune system, stopping it from attacking the foetus. More importantly, it increases her blood pressure, so that more blood pumps past the placenta and consequently more nutrients are available to the foetus.

The mother doesn’t take this foetal manipulation lying down. In fact, she pre-emptively reduces her blood sugar levels. She also releases a protein that binds to the foetal hormone, rendering it ineffective. So then the foetus further increases its production. By eight months, the foetus spends an estimated 25 per cent of its daily protein intake on manufacturing these hormonal messages to its mother. And how does the mother reply? She increases her own hormonal production, countering the embryo’s hormones with her own that decrease her blood pressure and sugar. Through all this manipulation and mutual reprisal, most of the time the foetus ultimately gets about the right amount of blood, and about the right amount of sugar, allowing it to grow fat and healthy in time for birth. This is the living instantiation of Haig’s tug-of-war between maternal and paternal genomes. As long as each side holds its end up, nobody gets hurt.

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But what happens when things go wrong? Since the turn of the millennium, the Human Genome Project has provided a wealth of data, most of which remains incomprehensible to us. Yet by looking for signs of genomic imprinting – that is, genes that are expressed differently depending on whether they are inherited from the father or the mother – researchers have been able to pin down the genetic causes of numerous diseases of pregnancy and childhoods.  Pregnancy Foetus Mother Essay.Genomic imprinting, and the maternal-fetal battle behind it, have been shown to account for gestational diabetes, Prader-Willi Syndrome, Angelman Syndrome, childhood obesity and several cancers. Researchers suspect that it may also underlie devastating psychiatric conditions such as schizophrenia, bipolar disorder and autism. In 2000, Ian Morison and colleagues compiled a database of more than 40 imprinted genes. That number had doubled by 2005; by 2010, it had nearly doubled again. Identifying genetic mechanisms does not in itself provide a cure for these complex diseases, but it is a vital step towards one.

Preeclampsia, perhaps the most mysterious disease of pregnancy, turns out to be a particularly good example of the way in which the evolutionary, genetic and medical pictures are all lining up. More than two decades ago, Haig suggested that it resulted from a breakdown in communication between mother and foetus. In 1998, Jenny Graves expanded on this idea, suggesting that it could be explained by failure of imprinting on a maternally inherited gene. It’s only in the past few years, however, that we’ve pieced together how this process occurs. Pregnancy Foetus Mother Essay.