Development

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Questions Received:

  1. What are homeobox genes?

  2. Does the placenta have a nerve supply?

  3. What are the risks associated with the placenta being torn from the uterus within 5-6 week of pregnancy?

  4. When a blood clot occupies ¼ of the placenta during the 6th month of pregnancy, what are the consequences for baby and mother?

  5. Can a cornual pregnancy be determined at 11 weeks by an ultrasound, and if so can the uterus be saved or does it have to be removed? I had an ecptopic pregnancy before and some of the right tube was removed.

  6. Why would a woman have two placentas but only show one baby on the ultrasound?

  7. I am searching for info regarding the benefits or experiences of the mother eating some of the placenta after birth. Can you direct me to some likely resources?

  8. What is a placental lake? Will it affect my baby?

  9. Twins: how does it happen? Why sometimes two separate sacs? Do twins have to occurred in only female family or only male family or both? Where to read about it?

  10. Needing a good resource to write a paper on growth and development from prenatal period to adolescence.

  11. What happens to fetal waste while still in the womb?

Responses:

What are homeobox genes?

22nd January 1998

These are genes that guide the emergence of shape and form in embryos.

You may be wondering about the origin of this rather odd-sounding name? All of these genes contain at some point along their length an identical sequence of 180 nucleotides. This sequence results in the proteins they code for being able to bind with DNA. This shared sequence was given the name homeobox, and therefore all the genes containing this sequence are called homeobox genes or homeotic genes.

As we know, genes are rather like recipes for proteins, and embryologists have been struggling to bridge the gap between what we know about genes and the elegant way in which embryos develop. How can information about amino acid sequences in proteins result in guiding the formation of, say, the left hand compared with the right hand, or a nose with a certain shape? Well, some progress is being made in answering that question.

Bicoid GradientMuch of the groundbreaking work has been carried out in the fruitfly - Drosophila. It was demonstrated that the early steps in fruitfly development are influenced by chemical gradients within the fertilized egg (zygote). Those gradients are generated by the synthesis of proteins, using information placed in the egg before fertilization. In the image alongside, a gradient of bicoid protein is shown by the red colouration which is most intense at the future head end of the fruitfly embryo. (At this stage, the fruitfly embryo is different from other embryos in that the nuclei - shown here as green dots - are free in the cytoplasm, forming a syncytium rather than being contained within distinct cells. However, cell boundaries appear soon after this stage.)

These gradients inform the nuclei (and cells) of their position and accordingly which of their genes to switch on or off. You see, although all the nuclei contain the same set of genetic information, individual cells use only some of the genes available to them, and differences arise between cells as they begin to make different selections from the genome.

After the initial steps in pattern formation have been taken under the guidance of the gradients, the homeobox genes take over for the next - more detailed - stage of development. These are genes that code for proteins which then control the activity of other genes nearby. Thus, the products of homeobox genes are transcription factors - they are genes that control other genes.

 

A peculiarity of homeobox genes is that they are arranged along the chromosomes in the same linear order as the regions of the embryo they are controlling. Genes at the beginning of the cluster control development of the thorax, those in the middle control development of the proximal part of the abdomen, while genes at the end of the cluster control the more distal parts of the abdomen. This was a completely unexpected finding.

Homeobox Genes

Since their discovery in Drosophila, homeobox genes have been found in many other species, including us. In each case, the genes seem to be arranged on the chromosome in the same order as the regions of the embryo whose development they control. So it seems that homeobox genes arose early in evolutionary history, and have been guiding embryonic development in animals and plants ever since.

Does the placenta have a nerve supply?

24th June 1998

This is an intruiging topic that is rarely referred to in textbooks about the placenta. Recall that the placenta is a joint venture between the mother and the baby, consisting of tissues from both partners, so potentially a nerve supply could come from either or both. Intuitively, one might expect maternal autonomic nerve fibres to be present in the endometrium, but how about the fetal side - do any nerves extend along the umbilical cord towards the placenta?

In the guinea pig, the uterus and its endometrial lining is provided with an extensive system of adrenergic nerves that are concerned with controlling the blood vessels, although the nerve fibres diminish in number in the neighbourhood of the conceptus during pregnancy (Owman, 1981). There is only partial restoration of the nerve supply after pregnancy. In the case of the human endometrium the picture seems to be rather different: there is a general lack of innervation to the blood vessels of the endometrium in both the nonpregnant and pregnant (Khong, Tee, and Kelly, 1997). This suggests that other mechanisms control maternal blood flow within the human placenta.

Evidence in support of a fetal nerve supply to the placenta has been put forward for several species, including the rat (Kalugina 1986) and non-human primates (Fox and Jacobson, 1969). In the case of the human placenta, the evidence seems to be more equivocal. For example, although Jacobson and Chapler (1967) detected what they interpreted as nerve trunks and nerve cells in the placental villi of stained and cleared samples of human placental tissue, more recent studies have concluded that there is no fetal nerve supply to the placenta (Fox and Khong, 1990; Reilly and Russell, 1977; Sexton et al, 1996). Interestingly though, it has been shown that placental tissues store and release the neurotransmitter acetylcholine in a similar way to nerve cells (reviewed by Sastry, 1997), and although the effects of the acetylcholine are unknown, it may help in some way to regulate blood flow through the placenta, influence amino acid transport across placenta, and affect the release of placental hormones.

So the answer to the question seems to be at present: no, there is not a nerve supply to the human placenta, either from the maternal or the fetal side. However, acetylcholine is stored and used in placental tissues in ways as yet unclear, although probably helping to control placental activity.

References

What are the risks associated with the placenta being torn from the uterus within 5-6 week of pregnancy?

26th January 1999

If the developing placenta becomes separated from the uterus so early during pregnancy, the main risk is that the embryo will die because it is no longer able to receive the materials it needs from the mother or dispose of its waste products. The level of risk will depend on the degree of separation - slight separation may be survivable. Remember that this is a period of rapid morphogenesis (development of form) for the embryo, and thus it is very sensitive to disturbances in its environment. The embryo is only about 1 cm long in the 5th week, and the overall diameter of the conceptus with the trophoblast about 4 times that size, so the risks of serious haemorrhage by the mother are small because the maternal blood flow to the implantation region of the uterus is only moderately increased at this stage. However, if premature separation occurs later in pregnancy, the risk of serious maternal haemorrhage rises.

In addition to trauma, some of the risk factors that predispose to premature separation later in pregnancy are high parity (ie: mothers who have had several babies already), pre-eclampsia, hypertension, and smoking. The clinical term for premature separation of the placenta is abruptio placentae.

When a blood clot occupies ¼ of the placenta during the 6th month of pregnancy, what are the consequences for baby and mother?

2nd February 1999

Localised blood clots are fairly commonplace in the placenta at term, and are a sign that the placenta has been working hard for the last few weeks of pregnancy and is beginning to 'age'. Generally the clots are of no real consequence in a clinical sense at that time. However, a blood clot at 6 months (placental abruption) is more worrying in the sense that it will reduce the area of the placenta available for exchanges between mother and baby, and the rate of the baby’s growth may become slowed. The size of the blood clot relative to the placenta is the key factor - if it occupies more than half of the placenta then immediate medical help will be required and probably immediate delivery of the baby. Clots of smaller sizes, as in this case, will have less serious consequences and complete bedrest - no getting out of bed except to bathe and use the toilet - is an effective conservative treatment. The length of bedrest will depend on the extent of the blood clot and any associated changes. With prompt attention and expert care, nearly all mothers and their babies survive placental abruption.

Can a cornual pregnancy be determined at 11 weeks by an ultrasound, and if so can the uterus be saved or does it have to be removed? I had an ecptopic pregnancy before and some of the right tube was removed.

16th March 1999

A cornual pregnancy occurs when the conceptus implants at the junction between the fallopian tube and the uterus, rather than within the main part of the uterus. (It is also known as an interstitial pregnancy.) By the 11th week of pregnancy, good endovaginal ultrasonography should be capable of revealing a cornual pregnancy as a thick, brightly echogenic, ring-like structure located at the upper outer part of the uterus, complete with evidence of fetal structures. However, the ultrasonic findings may not be conclusive in all cases.

Cornual pregnancy has traditionally been treated by laparotomy (opening of the abdomen) and either cornual resection (removal of the affected part of the uterus and attached tube) or hysterectomy (removal of the uterus). Recently, however, more conservative operations have been developed, and operative laparoscopy (keyhole surgery) is showing promise (Sasso, 1995; Batioglu, Haberal, Yesilyurt, and Ekici, 1997; Grobman and Milad, 1998). With these newer techniques, it should be possible to save the uterus.

References

Useful website: Advanced Fertility Center of Chicago (This will open a new browser window.)

Why would a woman have two placentas but only show one baby on the ultrasound?

12th April 1999

There would seem to be two possibilities here:

Placental Lobes

Many variations in the shape and form of the placenta are possible, and the presence of additional lobes or subdivision into two relatively distinct lobes rarely causes any problems for the baby or mother. In the earliest stages of placenta formation, villi are present across much of the outer aspect of the implanted conceptus. Usually, the villi on the most deeply implanted part of the trophoblast enlarge to form the placental villi, while the more superficial ones shrink and do not contribute to the placenta. It would only take small variation in this process of selection of the villi to result in a placenta with different lobes.

I am searching for info regarding the benefits or experiences of the mother eating some of the placenta after birth. Can you direct me to some likely resources?

14th April 1999

Mothers of most mammalian species ingest the placenta and some amniotic fluid after giving birth (placentophagia). The reasons for this are still something of a mystery, but several interesting observations have been made. Placentophagia could potentially have nutritional, physiological, immunological and behavioural effects. A useful review of earlier ideas can be found in (Kristal, 1980). More recent studies have shown that placentophagia accelerates the onset of maternal behaviour towards the young, and enhances ongoing opioid-mediated analgesia (reviewed in Kristal, 1991; see also: Kristal, Thompson, and Grishkat, 1985; Tarapacki, Thompson, and Kristal, 1992). The rat placenta also contains substances which modify the blood levels of pituitary and ovarian hormones (Blank and Friesen, 1980): in rats that eat placentae after parturition, serum levels of prolactin rise and progesterone levels become lowered compared to rats prevented from eating placentae.

Professor M.B. Kristal, Department of Psychology, State University of New York, Buffalo 14260 is one of the leading exponents of work into this topic.

References

What is a placental lake? Will it affect my baby?

16th April 1999

This is not a term we are familiar with, but may be referring to a situation that sometimes occurs when a larger-than-normal accumulation of maternal blood is detected in ultrasound images of the placenta. We have to remember that the normal placenta contains spaces through which maternal blood circulates, bathing the placental villi and allowing exchanges between the mother's and baby's blood. These are called the intervillous spaces. Sometimes, perhaps as a result of trauma or a physiological change, part of the placenta can become prematurely separated from the endometrial tissues and a larger blood-filled space is formed. This would show up on an ultrasound scan. Premature separation of this sort is called placental abruption, and the effects on the baby will depend on how much of the placenta is involved. Larger degrees of separation will reduce the efficiency of placental exchanges and put the baby at risk. If more than half the placenta is affected, then immediate medical intervention will be required and it may be necessary to deliver the baby. Where there is a smaller degree of separation the pregnancy can continue but it is advisable for the mother to reduce activity levels and perhaps have a period of bed rest. It would be helpful for you to receive more information from the person who identified the placental lake or the doctor who is monitoring your pregnancy so that you know more about the implications of the finding and how best to continue. However, it seems likely that if the finding was mentioned only in passing that the problem is relatively minor.

Twins: how does it happen? Why sometimes two separate sacs? Do twins have to occurred in only female family or only male family or both? Where to read about it?

22nd April 1999

There are two different kinds of twins:

Non-identical twins always develop in separate chorionic sacs - they implant separately in the mother’s endometrium. Identical twin may or may not have separate sacs. It depends on the stage at which separation of the original conceptus takes place. If twinning occurs very early on, for example by splitting of the two-celled conceptus, then implantation and chorion formation will take place separately. However, if subdivision occurs after implantation at the stage of formation of the embryonic disc, both babies will share the same sac.

Formation of Identical Twins

Twinning occurs in about 1% of deliveries, although the prevalence differs from one population to another. A genetic tendency seems to be involved. Occasionally monozygous twinning is incomplete, and the twins are joined together - conjoined twins. This occurs when two organising regions arise close together in the embryonic disc during the second week after conception, and the twins share developing organs and tissues. The name 'siamese twins' is sometimes used for conjoined twins. It was first used for the celebrated pair of conjoined twins, Chang and Eng Bunker, who died at the age of 63 in North Carolina, 1874.

Chang & Eng Bunker with Family

Most embryology textbooks have sections on twinning, for example:

Needing a good resource to write a paper on growth and development from prenatal period to adolescence.

22nd June 1999

It depends on the level at which you are working. A good starting point would be a textbook such as Thibodeau, G.A. and Patton, K.T. (1996) Anatomy & physiology (3rd edition). St. Louis: Mosby-Year Book, Inc. (Chapter 33: Growth and development, pp 1042-1065.)

What happens to fetal waste while still in the womb?

2nd December 1999

Fetal wastes such as carbon dioxide and urea are transported to the placenta by the fetal bloodstream and are passed across to the maternal blood. The mother then disposes of the waste products as she would her own. So the placenta is the main avenue for fetal waste disposal. However, the fetus rehearses its own waste disposal processes before birth so that it will be ready to take over effectively when birth occurs. The fetal kidneys begin excreting dilute urine which is voided into the amniotic cavity, being added to the existing amniotic fluid. Other materials also accumulate in the amniotic fluid, for example waxy vernix caseosa (secreted by the sebaceous glands of the skin), lanugo hairs, and dead and dying skin cells. Periodically, the fetus swallows some of this cloudy fluid into its digestive system and digests some of the materials suspended in it. Water, the breakdown products of digestion, and also the urea excreted by the fetal kidneys are then absorbed into the fetal blood circulating through the walls of the digestive tract. The non-digestible components of the swallowed fluid remain in the intestinal lumen and are moved on to the large intestine where they accumulate as a greenish faecal material called meconium. So meconium could be classified as a fetal waste that is not disposed of through the placenta but which will be excreted by the newborn baby as faeces after birth.

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