Course:BIOL250/The Evolution of Pregnancy in Placental Mammals
|The Evolution of Pregnancy in Placental Mammals|
|Class Schedule:||Tuesdays and Thursdays from 11:00am to 12:30pm|
|Important Course Pages|
- 1 The Evolution of Pregnancy in Placental Mammals
- 2 Sexual Behaviour of Placental Mammals
- 3 Genetic Evolution
- 4 Structural novelties
- 5 Birth and Development
- 6 Predation
- 7 Pathologies of placenta
- 8 Cells
The Evolution of Pregnancy in Placental Mammals
Nearly 300 million years ago (MYA) mammals diverged from lizard-like non-placental animals. Within the mammalian classes, 3 sub classes emerged. Less derived egg laying mammals Monotremes are basal ancestors of the more derived Marsupials and Eutherians. As a result, Marsupials and Eutherians are more closely related to one another and comparisons between the two show the dynamic evolutionary steps taken to achieve true gestation. In 300 BC Aristotle attempted to create a phylogenetic tree based on physiologic appearances. This later became known as the topological species concept [1a]. Aristotle grouped Marsupials and Eutherians together because of their shared reproductive characteristics, while Monotremes, although considered mammals by today’s standards, were grouped with true egg laying amniotes. Each subclass pursued different reproductive strategies behaviorally and structurally, leading to evolutionary novelties in their genetic makeup and fitness.
Sexual Behaviour of Placental Mammals
Sexual Selection has been around ever since there have been separate sexes. Sexual Selection is nonrandom reproduction of individuals resulting from differential access to mates or the gametes of mates. Sexual selection is the consequence of competition among members of one sex for members of the opposite sex. The competition among individuals of one sex for the opposite sex may center upon coaxing choosy individuals to mate or to use the competitive sex’s gametes, or the competition may simply focus on striving to obtain sexual access to receptive individuals who are willing to mate and reproduce. 
Females are strongly biased towards maternalism. Sexual behavior in females is not frequent and is characterized by a difference in male sexual behavior. Male sexual behavior involves finding a sexually mature female and competing aggressively for them with other males. An important component of maternal care is the need to recognize offspring, which in small-brained rodents is dependent on smell. Their sense of smell is well-developed and is essential for determining sex differences in reproductive behavioral strategies. Some odors such as those found in urine and amniotic fluid are primary contributers. Females form strong social bonds with their infants, and female-female relationships often encourage other females to help with care of offspring. 
Competition is a large aspect in male reproductive strategies. In male mountain goats, increase in age and body mass increases the ability to court estrus females, but has no affect on male to male competition. The level of competition between males remains consistent with age.  In a giraffe population a study was done that found adult males (Bulls) to be more likely to associate with and sexually investigate females (cows) when the females were in their fertile phase. Proximity between cows and bulls during this time was much more pronounced. Bulls are able to detect cues from the cows to determine her reproductive status. Male giraffes would adopt a roaming strategy that would enable them to search for females and mate-guard them with minimal metabolic costs. There are three major costs to the roaming strategy: metabolic expenditures while travelling long distances, increases mortality risk during these travels, and missed mating opportunities with other females when maintaining close association with a partner. It is thought that male giraffe have evolved with a roaming reproductive strategy for endurance rivalry, which impacts reproductive success, rather than male to male combat. 
In a small rodent-like marsupial thermoregulation is the main reason for seasonal variation in nesting group size. Sociality and sexual selection are linked. Some group in a harem where they can incite male competition, mate with the best males, and avoid attention from unwanted males. Females have a matrilineal fission-fusion social system, and males venture further in their lives trying to contact as many females as possible.  Marsupials are typically nocturnal in their habits and their social organizations are often relatively non-gregarious. Some marsupials are monogamous and only have one partner, while others are polygynous and have multiple. 
The echidna an example of an extant monotreme Echidnas are solitary creatures, with both sexes being promiscuous. Each animal has a range within which it lives, the range for males is larger than that of females. Echidnas usually stay in their home range, but do make further excursions on rare occasions.  In platypus, females dig an extensive burrow system during breeding season. As such it is unknown whether or not they mate with single or multiple partners. 
Mammalian sex chromosomes
Marsupials, monotremes and eutherians all have relatively the same size genome, however their karotypes are very distinguishing.(12) Interestingly, monotremes have the largest chromosomes but also have microchromosomes . The microchromosomes is what gives the monotremes reptilian like karyotypes. However, monotremes are unique in that the microchromosomes are unpaired and form a chain during meiosis.(9)(10) Their large chromosomes consists of X’s and Y’s, which pair over the short arm of the X and long arm of the Y . Furthermore, monotremes undergo homologous pairing. Marsupials on the other hand, have smaller X chromosomes, more similar to that of eutherians, and abnormally small Y chromosomes. Lastly, eutherians typically have a larger Y chromosome and X-Y pairing and recombination is crucial for correct mitotic segregation. (8)
A further look into the contrast between montremes and eutherians was done through multiple RNA sequence tests. It was found that around 1532 genes were expressed in placental males that were not conveyed in the marsupials. One of the first imprinted genes identified was the insulin-like growth factor2 (Igf2) and it’s receptor M6p/Igf2. This gene is seen to regulate embryonic growth as it is a potent growth factor [14. Eutherians, such as primates and mice have the Igf2 gene as well as its receptor. However, it is not found in the genes of monotremes . Furthermore, the marsupials binding ability of the Igf2 to the M6p/Igf2 is rather weak in comparison to the eutherians, which leads to the reasoning behind the typical underdeveloped young seen in marsupials .
In addition to the difference in binding affinity a fundamental difference between pregnancy in placental males and egg developing mammals such as marsupials, is that the endometrial stromal cells (ESCs) undergo decidualization in response to hormones, secondary messengers, and fetal signals. Decidualization is not seen in the monotremes because their endometrium is not expecting the implantation of an embryo. Of the 1532 genes only found in placental mammals, there is an abundant amount of genes found near the Eutherian-specific transposable element (MER20). The genes in this area have been found to be responsible for binding transcription factors essential for pregnancy.
With further examination of MER20, it showed that it could regulate RNA expression and thus could over express certain genes like G protein-coupled receptor (GPCR) which would lead to the recruitment of cAMP signaling pathway in the ESC’s. The cAMP pathway is very crucial because it helps coordinate the response of ESC’s to decidualization signals. This correlation built the theory that the placentation can be traced back 130 million years ago to certain group of mammals. The monotreme group were the mammals that did not have Igf2 or MER20 and did not produce live young but instead laid eggs similar to ancestral species. The eutherians were the mammals that had the genes that enabled the ESCs to allow for embryo implantation to occur, as well as having a high binding affinity of Igf2 leading to embryonic growth within these mammals. Lastly, the low affinity binding of Igf2 led to marsupials. 
The uterus is complex organ found only in females which allows for internal development of offspring in the animal kingdom. The uterus differs in structure and function throughout and within the 3 mammalian subclasses. A common function of the uterus in all subclasses is that it serves as a protective barrier from external hazards and provides an environment in which the embryo may develop for the complete gestation period.
Individuals of the less derived order monotremata are unique in that they are classified as mammals, but do not give birth to live young. Monotremes are didelphous . Much like birds, monotremes lay eggs and incubate them . Unlike birds however, monotremes incubate their eggs in a pouch that is homologous to a structure later discusses in marsupials . Unfortunately, not much is known about monotreme egg laying; scientists agree that when a female monotreme curls up, this position will align the cloaca with the pouch enabling her eggs to glide in easily so development may continue .
The types of uteri found in orders eutheria and marsupialia are very similar. They are both believed to have been derived from a common ancestor in subclass monotremata . As a result, eutherian and marsupial reproductive tracts are more similar to each other than to monotremes. Marsupials and eutherians have a highly vascularised uterus . To prepare for the implantation of an embryo, the uterus builds up a vascularised lining called the endometrium . As the endometrium grows in size the number and size of blood vessels within grow as well. These structures will eventually, along with the placenta, facilitate nutrient supply to the developing fetus.
Eutherians are mammals that give birth to live young after a prolonged complete gestation has taken place . Eutherians lack a pouch because their offspring are born fully developed. The uterus performs the same basic function as in marsupials – the key difference between the two subclasses is the degree of development of young inside the uterus. Eutherian uteri can be categorized by shape of the uterine horn . The uterus is more developed in eutherians because it houses the fetus for its full developmental term.
Marsupials can be thought of as the middle man amongst mammals. They have adopted structures from both primitive (monotreme) and derived (eutherian) organisms. The marsupial uterus is primitive in comparison to the eutherian uterus. Marsupials give birth to altricial underdeveloped offspring. Infant marsupials climb the mother’s fur and latch onto a teat burrow in a softly lined pouch where they will continue to develop . The uterus found in marsupials is unique in that it is responsible for secreting a substance called “uterine milk” which, along with the placenta nourishes the developing fetus . This is not seen in monotremes and eutherians.
The placenta is arguably the single most important organ affiliated with gestation. As previously discussed subclass eutheria and marsupialia diverged from subclass monotremata. Because monotremes are egg laying mammals, they lack a placenta. The complexity of the placenta increases from marsupials to eutherians. The placenta is a highly vascularized organ linking mother to fetus via the umbilical cord. In viviparous mammals, placental functions are essential for fetal survival.
Since both the placenta and fetus are alien to the mother’s body, her autonomic immune system is programmed to attack and destroy them both . To counteract this, the placenta emits a hormone that suppresses the mother’s immune response and essentially allows for continuing development . In both subclasses, the primary function of the placenta is to mediate nutrient and gas exchange from mother to fetus . The placenta is not an impermeable barrier. It works through simple diffusion, preventing the passage of large molecules, bacteria and most xenobiotics to the fetus . Amino acids synthesized by the mother get recruited by the placenta to promote development of the fetus . The placenta does not only bring molecules in, but it also excretes metabolic waste and keeps the environment in which the fetus is developing in clean .
The eutherian placenta is thought to be the most derived of the mammals because marsupials have limited internal contact between mother and fetus . Marsupials are described as having a choriovitelline placenta, which is more like a glorified yolk sac; whereas eutherians contain a unique and highly specialized chorioallantoic placenta . A eutherian’s placenta not only promotes pregnancy through hormones and provides nutrients, but it also facilitates respiratory transportation from mother to fetus – this is not observed in a choriovitelline placenta . Since the duration of gestation is generally longer in eutherians, the placenta functions to physically anchor the fetus to the uterus to keep it in the uterus for continued development .
It is important to note the way in which the placenta allows for the passage of large amounts of nutrients. Many finger like projections called villi litter the placenta. These villi function almost identically to those found in your intestines. The villi greatly increase the surface area of the placenta; a larger surface area mediates the easier passage of nutrients . Placentae can therefore be categorized based on the distribution of villi . Horses and pigs have a diffuse placenta what is characterized by having villi scattered evenly throughout the entire structure . Ruminants have a cotledonary placenta, which is characterized by having clumps or patches of villi . A discoidal placenta is described as having one or two disk shaped areas of villi as seen in rodents . And finally a zonary placenta is described as having continuous bands of villi as seen in carnivores . In both eutherians and marsupials the placenta may also be categorized by the rate and efficiency of gas and nutrient exchange between mother and fetus .
Eutherian chorioallantoic placentae are the most derived and as such, they have a classification system unique to their own subclass. The chorion is a multi layered membrane that forms around the fetus during pregnancy. The degree of placental attachment to the chorion and subsequent degradation of the chorion determine this system of classification . This classification is unique to eutherians because of the evolutionary structural and functional advances it has made from marsupials .
Class mammalia was named after the characteristic specialized epidermal glands found in mammals: mammary glands . Although it is not entirely understood how mammary glands evolved, it is generally agreed that monotreme and marsupial mammary glands are internally structurally internally (mammology blue griffithis). Monotremes have the most primitive form of mammary glands amongst all mammals. No adipose tissues are centered and build around/under the gland to raise it up and it lacks a nipple . During feeding, milk flows from the glands spread throughout the female’s abdomen where offspring are able lap it up .
Eutherians have mammary glands and true nipples for feeding. The evolutionary trade off between gestation and lactation is most interesting between eutherians and marsupials. Firstly, it is important to note that lactation is extremely energy costly – even more so then gestation . Females not only have to meet their body’s own demands, but also those of their growing offspring. Marsupial gestation is in general much shorter then eutherian gestation. Researchers have speculated that this is meant to minimize the dangers associated with prolonged pregnancy . In order to make up for this, marsupials have a much longer lactation period then eutherians . Because more of the marsupial’s energy is allocated to lactation rather than gestation, this leads to the continual degradation of the mother’s energy supply. On the counter balance, eutherians allocate much of their energy in gestation rather than lactation. To deal with the stresses of pregnancy some eutherians – i.e. llamas, have set periods of infertility to give their bodies some much needed rest .
Birth and Development
The evolution of viviparity and oviparity are closely linked. It is likely that ancestral mammals were originally oviparous, as there are still mammals today that lay eggs, such as the platypus . Viviparity began to evolve when females no longer layed an egg before the fetus had come to term . Instead, the placenta eventually developed and took over the function of the yolk in an amniotic egg. In order for larger organisms to appear, something else had to be developed to take the place of the egg. The larger the placenta, the more nutrients available to the fetus, but an egg is limited in size .
Monotremes technically do not possess a vagina. Instead, there is a single opening in which the organism urinates, defecates and reproduces. Marsupials develop a placenta-like structure during pregnancy but cannot quite be classified as placental mammals . The largest group of mammals is Eutheria, the true placental mammals. The first discovered placental mammal was Eomaia scansoria, and it was also the first mammal in which the possibility of true vaginal delivery was present .
Humans have a very different delivery system than primates. The human birth canal angles forward and delivery requires a complex mechanism of fetal rotation inside the pelvic cavity because of adaptations to bipedalism and large brain size . Primates have a much simpler form of a birth canal and a less complex delivery. A fetal human head will change shape slightly during birth to account for the large size. The human pelvis is also three dimensional while the primate pelvis is long and flat . Evolutionary development of larger offspring with larger brains caused these changes in the pelvic region of humans.
Eutherian mammals show a vast diversity in the level of development reached by the time of delivery. After birth, the parental care put into an offspring changes from species to species depending on its development. Producing altricial offspring holds an advantage because less energy is spent by the mother during the pregnancy stage due to the low birth size and short gestation period . The care put into the offspring can also be shared by another organism after birth, usually the father. Precocial offspring on the other hand would take more prior investment, but far less investment after birth. A greatly developed offspring is also less vulnerable to predators. For example, zebras are very precocial and learn to walk only minutes after they are born .
Growth rate after birth varies throughout mammals. Precocial offspring tend to grow much quicker earlier in their life after birth than altricial mammals. Some mammals experience a growth rate peak a bit after birth but others decelerate in growth rate, their highest rate being just before or just after birth .
In placental mammals, death of one frequently remains concomitant to that of the other, meaning if one dies the other dies also if carried internally, but that is less frequently the case with pouched babies, also referred to as marsupials. In this case the mother dies and the baby can still survive, this benefits marsupials in predation of the mother, and the offspring still able to survive.  Both these types of mammal have the risk of the baby’s mortality if the mother is hunted and killed. In contrast, the monotremes have risk of the eggs they lay being hunted as food, but if the mother dies, the offspring can still survive, similar to marsupials, but are not as linked. Once the egg hatches it is an immature stage of the animal, and can still be hunted by predators easily, since it is less developed, similar to the marsupials offspring will be immature and underdeveloped at birth. Whereas placental mammals’ offspring are less likely to be hunted because they are more developed. The larger the child at birth; the more difficult the delivery is for the mother, this is not problematic for marsupials and only for long gestational period placental mammals. The larger child could cause the mother to be unable to avoid a predator, and decrease survival rate.
Pathologies of placenta
Though the evolution of the placenta may be advantageous, it comes with some negative pathological effects that can occur as well. There are 3 major pathologies and 2 major infections of the placenta which can have serious negative effects, these are not the only problems, pathologies and infections but are some major ones. Placental accreta is the most common of the defects it can occur in approximately 1:2,500 pregnancies. It is caused by the abnormally deep attachment of placenta, through endomentrium into myometrium. It’s classified into 3 subtypes, accreta, the most common, increta, and percreta, the least common. It is likely for haemorrhage during placenta removal, and commonly requires surgery to stem the bleeding and fully remove placenta. This pathology can result in death. Placental praevia is another pathology, less likely to occur, and is classified by abnormal vascularisation of the endometrium caused by scarring or atrophy from previous trauma, surgery, or infection. This only occurs in a mere 0.5% of all placental pregnancies. Placental abruption/abruption placentae are also very uncommon, it occurs in about 1% of all pregnancies. It is classified when the placental lining separates from the uterus. This has a mortality rate of 20-40%, significant contributor to maternal mortality. The two common infections are known as placentitis and chorioamnionitis. Placentitis is an infection passed from the mother to the fetus and can lead to severe fetal anomalies or fetal loss. This infection is from the maternal blood supply and passed to the fetus via the chronic villus. Chorioamnionitis is an inflammation of the fetal membranes due to bacterial infection. It involves immune cells responding to the site of infection in the fetal membranes.[ Other mammals use the yolk style method to give birth to their offspring and do not supply their own nutrients and as many immune cells. The marsupials and monotremes are more susceptible to infections when they are born, due to less development, and less passing of maternal immunity than eutharians.
The placental consists of 10-40 cotyledons, varying on the species, with the main one being the chronic villus, which is the site of exchange of circulation between maternal and fetal blood supplies. The thin outer layer of ectoderm that encloses the embryo of mammals and attaches the fertilized ovum to the wall of the womb and absorbs nutrients is called the trophoblast layer. The composition of the trophoblast layer in the human placenta changes during pregnancy. During the first trimester, the villi have a nearly complete cytotrophoblast layer underneath the syncytiotrophoblast layer. Later in the pregnancy, the cytotrophoblast layer becomes discontinuous. Immunoglobulin G (IgG) is the important antibody that can cross this membrane and generate immunity for the fetus, from the mother’s immune responses. The fetus uses the maternal amino acids to get its proteins from protein synthesis. These both show how important the maternal cells are to the fetus developing inside the mammal. Certain cellular modification that must be achieved in succession can cause the placental mammals and marsupials to revert to one another under certain stress situations.
1a) Singer, C. (1931) A history of Biology to About the year 1900 A general introduction to the Study of living things. Ames, Iowa: Iowa state university press.
1) M.H. Nitecki, J.A. Kitchell, Evolution of Animal Behavior: Paleontological and Field Approaches. (08/1986), pp 113
2) W. Goymann, H. Hofer, Animal Behavior: Evolution and Mechanisms. (2010), pp 483
3) E.B. Keverne, Genetics of Sexual Differentiation and Sexually Dimorphic Behaviors Genomic Imprinting and the Evolution of Sexual Differences in Mammalian Reproductive Strategies. Advances in genetics (2007)
4) F.B. Bercovitch, Sociosexual behavior, male mating tactics, and the reproductive cycle of giraffe Giraffa camelopardalis. Hormones and behavior (2006)
5) D.O. Fisher, The evolution of sociality in small, carnivorous marsupials: the lek hypothesis revisited. Behavioral ecology and socio-biology. (2011) pp 593
6) S.C. Nicol, Spatial ecology of a ubiquitous Australian anteater, the short-beaked echidna. Journal of mammalogy (2011)
7) R.W. Rose, Testes weight, body weight and mating systems in marsupials and monotremes. Journal of Zoology. (1997)
8) Burgoyne P. S., et al. (1992). Fertility in mice requires X-Y pairing and a Y-chromosomal “spermiogenesis” gene mapping to the long arm. Cell, 71, 391–398.
9) Murtagh C. E. (1977). A unique cytogenetic system in monotremes. Chromosoma, 65, 37–57.
10) Wrigley JM, Graves JAM. (1988). Karyotypic conservation in the mammalian order monotremata (subclass Prototheria). Chromosoma, 96, 231–247.
11) Lynch, V. J., et al. (2011). Transposon-mediated rewiring of gene regulatory networks contributed to the evolution of pregnancy in mammals. Nature Genetics, 43(11), 1154-1161.
12) Graves, J. A. (1996). Mammals that break the rules: Genetics of Marsupials and monotremes. Annual Reviews Genetics, 30, 233-260.
13) Hore, T. A., et al. (2007). Construction and evolution of imprinted loci in mammals. Trends in Genetics, 23(9), 440-448.
14) Jonh, R. M., et al. (2000). Genomic Imprinting, Mammalian Minireview Evolution, and the Mystery of Egg-Laying Mammals. Cell, 101, 585-588.
15)Vaughn, T. A., Ryan, J. M., & Czaplewski, N. J. (2000). Mammology. New York, United States of America: Saunders College Publishing. 16) Feldhamer, G. A., et al. (2007). Mammology: Adaptation, Diversity, Ecology. Baltimore, United States of America: John Hopkins University Press. 17)Delany, M. J. (1982). Mammal Ecology. New York, United States of America: Blackie and Sons Limited. 18) Tovell, W. (1973). The Illustrated Natural History of Canada The Nature of Mammals. Toronto, Ontario: Natural Sciences of Canada Limited. Ramsey, E. M. (1982). The Placenta: Human and Animal. New York, United States of America: Praeger. 20) Parente, R. C. M., Bergqvist, L.P., Soares, M.B. & Filho, O.B.M. The History of Vaginal Birth. Arch Gynecol Obstet, 284, 1-11. doi: 10.1007/s00404-011-1918-6.
21) Ferner, Kirsten, Mess, Andrea. (2011). Evolution and Development of Fetal Membranes and Placentation in Amniote Vertebrates. Respiratory Physiology and Neurobiology, 178, 39-50. doi: 10.1016/j.resp.2011.03.029.
22) Coan, P.M., Vaughan, O.R., Sekita, Y., Finn, S.L., Burton, G.J. & Constancia, M. (2010). Adaptations in Placental Phenotype Support Fetal Growth During Undernutrition of Pregnant Mice. The Journal of Physiology, 588.3, 577-538. doi:10.1113/jphysiol.2009.181214.
23) Case, Ted J. (1978). Endothermy and Parental Care in the Terrestrial Vertebrates. The American Naturalist, 112, 861-874. Retrieved from http://www.jstor.org/stable/2460163.
24) Gaillard, J. M., Pontier, D., Allaine, D., Loison, A., Herve, J.C. & Heizmann, A. (1997). Variation in Growth Form and Precocity at Birth in Eutherian Mammals. Proceedings: Biological Sciences, 264, 859-866. doi: 10.1098/rspb.1997.0120.