Twin pregnancies and the role of telomers

This topic has been presented at the XXVI Congress of Perinatal Medicine
St. Petersburg 05-08 September 2018

If we consider the series of losses that accompanies the human being’s life, and if we go back, looking for a first trace engraved in the “cellular memory”, we end up by facing one of the most interesting discoveries of molecular biology: telomeres.

The discovery of telomeres and the knowledge about their functions has allowed a greater understanding of the aging process and its correlation with the so-called stressful events.

In 2009 Blakburn, Greider and Szostak received the Nobel Prize for medicine for their studies on telomeres and telomerase, but we must recognize that, as early as 1973, Soviet biologist Olonvikov had already discovered the compensatory mechanism of telomerase and advanced hypotheses about its function in some degenerative diseases (tumors).

Telomeres are portions of chromosomes, a sort of protein caps, located at the end of the chromosomal arms, whose DNA does not encode proteins. DNA is not completely replicated and this causes a shortening of the chromosomal ends at each replication cycle.

The telomeres of the chromosomes of the cells in proliferative activity are therefore progressively shortening; when their length goes below a critical threshold, which is between 50-70 cell divisions, cells become senescent and cell division stops.

Telomerase is the enzyme that is opposed to this process of shortening through a reverse transcriptase mechanism. The telomerase is an enzyme, which re-lengthens the shortened telomeres, in order to keep the chromosomes intact.

In the human species, telomerase is active in germ cells, stem cells and cancer cells, but not in somatic cells (which represent most of the cells in our body). We are therefore faced with a natural aging process witnessed by the shortening of telomeres.

Do telomeres get shorter only because of aging?

Other researches have shown that various factors, such as stress and depression can lead to shortening of telomeres, causing premature aging and profoundly affecting life expectancy.

Dr. Epel ( 2009)  from the University of California, has clearly highlighted that the shortening of telomeres is even more pronounced under conditions of stress compared to the normal aging process.

The hypothesis was tested by measuring the length of telomeres of mothers of children with chronic diseases and finding that they were significantly shorter than those of mothers with healthy children.

A group of researchers (Kortshal & coll. 2010) from Vienna’s K. Lorenz Institute have developed an interesting experiment on rats, trying to verify the opposite hypothesis, i.e. that mothers with shorter telomeres gave birth to children with chronic conditions.

Wild rats were selected, excluding laboratory ones, which were the result of several generations of blood relatives. In fact, these lab rats have longer telomeres because they live in a protected environment. Even this condition is not universally confirmed because a medium-type competitive activity should activate the telomerase and consequently the telomere repairing mechanism. However, common rats with common telomeres were chosen in this experiment.

Three groups were assigned:

Group  n. I consists of two sisters, who lived in a protected environment with plenty of stimulating objects and elements;

Group n. II consists of another sister and a related male. Here the litters were withdrawn very early in order to encourage a state of almost permanent gestation, which imposed a significant metabolic stress.

Group III: only young male rats were withdrawn, leaving the females. The population increased and so did the stress due to metabolic causes of continuous pregnancies, but also to the overcrowded and competitive environment.

The experiment verified that groups of females n.2 and 3 (stressed) had shorter telomeres.

On the other hand, the females of the first cage (those who were alone with the toys), and males of the second group (those who were continuously sexually active, since pups had been removed from the cage and thus the period of anestrus was shorter) had longer telomeres.

So, the experiment seems to indicate that the stress of pregnancy, competitiveness and overcrowding, shortens the telomeres of the females, while a continuous sexual activity provokes lengthening of telomeres in males. As a matter of fact, male rats in laboratory did not have to wonder about lack of food or about other dangers. It is interesting to point out the particular reaction of the females, forced to continuous pregnancies: even if they were in no stressing conditions, they had short telomeres.

Taking into consideration the parameter ‘telomere length’, as an index of cellular aging, we could say that while sexual activity and the protected environment promote the good health of the male, subsequent motherhoods are a stress factor for female and induce their premature aging. It is possible that this fact is also supported by the increase of free radicals, produced in the gestation and the breastfeeding. In fact,free radicals reduce the effectiveness of the remedial action of telomerase on telomeres.

We could confirm here, with biomolecular data support, that the ambivalent antagonism between drive of self-preservation and drive of species conservation has a psycho-biologically marking, which is measurable and transmissible.

I would like to underline the word ” transmissible”, because the trauma modifies the structure, in this case genetic with epigenetic mechanism, highlighted with the shortening of telomeres. We should consider also the traumatic complex which could be represented by the situation of prolonged stress, such as the one suffered by mothers who care for children suffering from chronic diseases).

According to this hypothesis trauma is transmissible to following generations. Psychoanalysis and later micro-psychoanalysis have argued that the trauma is inscribed in the so called ID, considered to be the energy reservoir of psychic life, a pre-psychic and pre-somatic hinge between thrust and motility of the drives. Today we can assume that telomeres represent a pathogenetic mechanism of trauma fixation.

Moreover, this hypothesis does not surprise if we consider that Freud had always highly trusted discoveries of other scientific disciplines. In his early works he wrote:

“Psychoanalysts never forget that psychic elements are based on organic ones, although their research can only lead them to the psychological roots and not beyond”

Thanks to the discoveries of telomeres and the functioning of telomerase, being psychoanalysts,  we assume that  psychoanalysis, which leads to an improvement of the subject through the elaboration of unconscious elements and the abreaction of affection from deep traumatic nuclei, can go in the same direction of telomerase, i.e the lengthening of chromosomes (It would be interesting to measure telomeres after analysis or step by step) Let’s see what the recent experience of a pair of astronauts and the movements of their telomeres can show us.

In few words: one of the twins Kelly, both NASA astronauts, spent 215 consecutive days in space, while his brother Mark remained on Earth. The data are still being studied, however, in Kelly were found important alterations in gene expression and DNA methylation. These data confirmed how the environment can influence genes according to epigenetic mechanisms. The alterations detected are similar to those observed when people are subjected to severe stress, changes in the environment or food and sleep habits. Nevertheless telomeres had lengthened, in comparison to those of Mark, the twin who stayed home. Once Scott Kelly had returned to Earth, the length of his chromosomes had returned to pre-launch levels, i.e. same length of the co-twin. Researchers are still working to understand what it means. At the moment any hypothesis is risky.

1. We could say that sometimes space is better than everyday life…

We can only consider that stress and telomeres have a dose/answer relation: a small dose of stress does not affect telomeres’ length. On the contrary, short-term manageable stressors can even improve the remedial activity of telomerase, while high dose of chronic stress, dragged on for years, can be dangerous.

1. This was highlighted by Blakbourn’s studies on women subjected to mistreatment and abuse, in comparison to not battered women. The author had irrefutably demonstrated the relationship between maltreatment and the reduction of telomere length
2. During the same study he also demonstrated a direct relationship between maltreatment and the value of BMI (Body Mass Index) in relation to bulimia suffered by the battered women of the sample in question: an example of correspondence between suffering displayed on the somatic level and suffering expressed on the psychic level).
3. Let’s see what happens for another highly diffused psychiatric pathology, the most widespread indeed: depression.

Depression often occurs in families. Not only daughters of depressed mothers are more prone to this disorder, but, even before depression occurs, they have shorter telomeres of blood cells in comparison to those of not depressed girls.

Probably in the case of depression the arrow goes in both directions: short telomeres could precede depression and depression could accelerate the shortening of telomeres. Of course, depression is a multifactorial disorder. And the sense of guilt is its most common expression (in addition to mood decrease, sometimes sustained by sense of guilt).

The case we’ll mention indicates how mother’s experience of loss, and moreover her sense of guilt for the supposed death of a twin, has affected the response of the surviving child.

1. is a 15-year-old girl with a bulimic-like DCA. As a matter of fact, the young girl suffers of dyspeptic experience: she can’t stand the annoying noises produced by those who eat, chew or swallow next to her. She lives socially isolated and has almost abandoned the school.

The story of the anamnesis with her mother’s reconstruction leads to a series of revelations that leave the girl very surprised: the gestation of A. had presented difficulties with threats of abortion. Her mother had to rest for the entire pregnancy. Moreover, it seems that the pregnancy had begun a few weeks earlier (as evidenced by the rise of Beta HCG), while on ultrasound the girl showed a much lower age. According to the obstetrician who did the ultrasound, there was another fetus that disappeared. Naturally there are no conclusive elements of this affair

However, we know that at least 1 pregnancy out of 8 has a twin start. The use of large-scale ultrasound has made it possible to highlight this condition which results in the loss of one of the two conceived within the first quarter. However, this loss is not without risk for the survivor who may present embryonal damage or fetus-fetal or fetus-placental anastomosis. Consequently, this could lead to release of thromboplastin and consequent risk of Disseminated Intravascular Coagulation = death.

In the exposed case, A. was the witness of her mother’s tale about the existence of a twin who later disappeared. It is a representation which her mother had since the first ultrasound. We can assume that the unconscious relation with her mother has included the presence and the disappearance of a twin.

This metapsychological hypothesis is much different from the idea of a proto-relation between the survivor and the missing twin. By following N. Peluffo’s researches on pre-natal life, we can only hypothesize that the mother’s experience of presence/loss of a second embryo/fetus, may have influenced psychic intrauterine experience of A., by stimulating the formation of a non survived co-twin image. This image could have stimulated in the girl a deep sense of guilt, being the survived baby.

Somatic and psychic symptoms of the girl could be considered in the light of this hypothesis, as the result of a non-differentiated proto-relation with her mother (the pregnant mother).

Of course, the acoustic disperception of the girl should be considered as an alarming sign of psychosis for follow-up consultations.

The interest of psychoanalysis for twins’ life before birth is relatively recent. It had a major impulse with the widespread of ultrasound, but especially with the increase of medical assisted pregnancies in which the probability of twin and multiple gestations is greater than in natural pregnancies. The Italian psychoanalyst who gave the greatest contribution to the knowledge of twins’ prenatal life is undoubtedly A. Piontelli.

In the 80s Piontelli began a systematic observation of 4 pairs of twins (3 DZ and 1 MZ) starting from 18/20 weeks of gestation up to 4 years after birth. Such punctual watching allowed the researcher to discover the continuity of many behavioral modules before and after birth and to hypothesize the existence of a strong influence of intrauterine experiences on postnatal life, also in relation to the presence of the co-twin.

It must be said that in those years, in relation to fetal life, there were very discordant positions among scholars of various disciplines, including psychoanalysts.

On one hand there were those who argued strenuously that child born with no knowledge at all and that the first relational experiences take place after birth. On the other hand, there were those who began to emphasize the effects of mother’s lifestyle and emotions on the fetus and on the subsequent development of the child.

This position which, incidentally, still appears to be prevalent, although constituting a progress compared to the previous one, nevertheless continues to consider the fetus as a passive stimulus receptor.

Finally, there were the micropsychoanalytical hypotheses of N. Peluffo, published in early 1976, about the existence of a mother-fetus psycho-biological interaction defined as “holding-expelling dynamic”. Traces of such early relation could be found in dreams, in some psychopathological conditions and in analytical transferal relays.

Piontelli, who continued in the following years to deal with fetal life, and in particular with twins’ fetal life, has maintained an extremely rigorous position of cautious reader and interpreter of the motor patterns, recorded in the observation sessions of the ultrasound images.

In a more recent paper (2007) Piontelli emphasizes the necessity to stick to the facts and supports the idea that “… fetal behavior can only provide an indication of what the fetus does and does not do.”

For example, the movements of the fetus (startles, general movements, partial movements, respiratory movements, swallowing, etc.) can be considered only precursors of the most complex postnatal activities. Piontelli doesn’t agree with those who have attributed intentionality to fetal movements.

In regards  twins, on whose supposed interactive abilities many colleagues have based hypotheses of pre-natal traumatic experiences due to the loss of the co-twin, Piontelli considers  that it’s impossible to determine whether the experience of loss expressed in adult life is attributable to such remote experiences or rather belongs to mental constructions of post-natal life.

However, the prolonged observation of twins’ fetal movements has allowed Piontelli to register the presence of tactile stimulation within the twin pair, starting from the eleventh week in the monochromic twins and from the thirteenth in the dichorionic pregnancies.

Moreover, from the fifteenth week, about one third of fetal movements were recorded as a  reaction to the co-twin stimuli. This is due to the reduction of space in the womb.

The uterine environment conditions are very different for twins who grow at different rates and, as a rule, one grows at the expense of the other. In some cases, such situation involves the death of one of the twins or the early termination of pregnancy, just to prevent the death of one or both. The twins occupy very different spaces. They have their own umbilical cord and, in the case of dichorionic twins and / or dizygotic (which are the majority), two different placenta.

Therefore, they are also subject to different proprioceptive stimuli and sensations. In any case, they present a very large amount of stimulus / response patterns with the co-twin and the continuity of these same patterns in post-natal life.

Another interesting fact concerns the diversity of behavior between one twin and another, which Piontelli has also verified in the observations after birth. These data have stimulated the hypothesis that hints of temperament already exist in pre-natal life.

These precious data, certainly do not authorize us to argue that during intrauterine life complex relational patterns are structured. Neither we can affirm that, at this age, it is possible to recognize the other, in the sense that we are accustomed to attribute to these expressions.

We are psychoanalysts, deeply aware that the recognition of another person presupposes first of all the awareness of oneself and that these skills are not acquired before the second year of life. Neither we agree with the concept of “prenatal grief”, referring to those twin pregnancies in which, within the first trimester, one of the two embryos / fetuses dies and is reabsorbed either by the placenta or by the other fetus.

Nonetheless, information on fetal skills increases day by day; those concerning, for example, the ability to recognize sounds (music, the mother’s voice) heard during gestation, in post-natal life. These data confirm the existence of receptive structures and recording of sensorial stimuli.

A new study, conducted by University of Maryland neuroscientists (P. Kanold et al., 2017), has identified for the first time a mechanism that is able to explain an early link between sound input and cognitive functions.

The fetus also has a chemical sensitivity, ie it can perceive tastes and smells.  Taste and smell do not depend directly on the fact that you eat or breathe. They are determined by a chemical mechanism, which depends on the presence of sensitive receptors to certain liquid or gaseous molecules in early stages of pregnancy and on peripheral stimulation that will allow these receptors to function. (Il feto e i suoi sensi Dipartimento Materno-Infantile U.O. Neonatologia e Terapia Intensiva Neonatale Direttore Dott. Paolo Tagliabue).We cannot knowfor sure if the fetus has gustatory and olfactory perceptions, but we know that in the uterus, the baby is immersed in particular odors (the mother’s diet regulates the amniotic fluid that gives the baby taste and olfactory stimuli) and therefore he can appreciate flavors belonging to his mother’s eating habits.Furthermore, in the amniotic fluid there is also his own urine that he swallows and whose chemical composition depends on what his mother eats. In other words, we’re entitled to think that the fetus has the ability to memorize the sensory and motor stimuli received from the uterine environment and the traces of its own sensory-motor activity. Such memory could remain silent after birth life, because sensory and motor patterns are substituted by more complex activity. Nevertheless, it could be reactivated in coincidence of similar stimuli.This reactivation could trigger the resubmission of the same pattern or response, in the form of investigation, relax, defense or other instinctive behaviors. It could be the case of sound, olfactory and motor stimuli like startles whose representation could be argued.

The startles are spontaneous and sudden snapshots of the whole fetal body, lasting one second. They have endogenous nature, present till the thirteenth week and then replaced by general and particular movements, but are still registered in the newborn and sometimes in the adult in the phases preceding sleep.

However, we must underline, that our main field of observation is the psychoanalytical session and clinical material is represented by the verbal and affective expressions used in the therapeutic relationship.

In therapeutic relationship, we observe the constant re-presentation of relational models, memories, mental representations and emotions, already experienced in previous periods of the subject’s life, in relation to meaningful people and in situations that have left a trace in their psyches.

Therefore, data of other scientific areas, collected by colleagues, are useful and indispensable in our work, in order to support our interpretations or refute those of projective nature.

We would therefore like to bring to your attention two clinical cases of twin gestations, one of which with heterologous fertilization.

The case of B.: a dizygotic twin

The girl suffered a gender identity disorder: she often saw her reflection in a mirror or window and doubted whether she was a boy or a girl. In fact, the girl used unisex clothing and had male movements. Born from a twin pregnancy DZ, the girl that I will call B., had a brother with whom she had lived in symbiosis till adolescence, including intimate sexual contacts. At the age of 16 her brother found a girlfriend and B. had a deep feeling of abandonment and betrayal, together with the sense of guilt, because of the sexual contacts.

Sexual contacts consisted in rubbing of the genital organs by imitating the sexual act. Mary was enough satisfied, because she could reach orgasm, while the brother remained unsatisfied. Mary’s sense of guilt for the sexual pleasure had several preconscious over-determinations.

Since she was a child she had been physically stronger and much more lively than her brother: in games, sports and school performances. Moreover, according to family tales, already in the womb B. was the largest and most active fetus.The brother accused B. of having occupied most of the place and of having stolen nourishment from him.  B., on the other hand, had a feeling of deprivation and castration that she attributed to the female gender.

When B. started psychoanalysis, her sexual-aggressive desire was to obtain what she had felt deprived: nourishment, space, penis and a dual relationship with her mother. In different stages of development, the desire was characterized by oral, anal or genital components, that provoked  strong feelings of guilt.  There were several symptomatic manifestations of this sense of guilt: in childhood M. had refused food (fortunately for a short period) for fear of dying from suffocation. Later on, in adolescence and early adult life M. had suffered of inhibition of sexual-affective relationships, due to the doubt about her identity and sexual orientation.

The study of photographs was decisive for the resolution of the doubt. In particular, we concentrated on one photo, portraying the naked twins at the age of two.  Maria managed to externalize her own aggressiveness toward her brother and in the transferal relation toward the analyst. She could express the unfulfilled desire to obtain the magical compensation to all she felt deprived of.

Probably, the long micropsychoanalysis sessions had made possible for the first time the experience of the exclusive relationship with the mother. It was her relational space and place, without the interference of the co-twin. In fact, even after birth, the couple had continued to share the bedroom: a bookcase separated their space, as well as in the uterus, where they were separated by the thin membrane of the amniotic sac.

The intrauterine experience had presumably also provoked the development of claustrophobic symptomatology that the girl relived in the session by expressing intolerance and desire to escape. The solution to the conflict was realized when B. could establish a stable sentimental relationship.

P.’s twins: a case of heterologous fertilization

Despite technological advances, these pregnancies always present many problems for the health of fetuses and for the psycho-physical commitment of the pregnant woman. Moreover, we should consider the involvement of the partner and other relatives. The couple who faces this difficult decision, first of all, has to overcome the sufferance of not being able to conceive a child naturally. The two partners must face several emotions such as frustration, anger, the sense of inadequacy and failure, now turned towards themselves, now towards the outside. In other words, each partner can alternatively consider himself responsible of the castration, or can project the responsibility on someone else: the other partner, parents, doctors or health personnel.

Frequently the mother is considered to be responsible for sterility: she is the person who has generated a defected daughter or defected son.

Another important problem concerns the mother-child/children relationship. Feelings of foreignness have been registered especially in heterologous fertilization cases.

The case that we will discuss concerns a young woman who lost fertility at a very young age and underwent a heterologous fertilization. We’ll call her P. After careful research a compatible donor was identified and fertilization took place. The result was 6 embryos, of which 3 were implanted in the womb and the others frozen to be used for another pregnancy, or to be donated to other sterile couples. The pregnancy had some complications: all 3 embryos had taken root, but doctors recommended embryo reduction, to avoid the risk of malnutrition of fetuses and danger to their health. What a difficult decision to make: there were risks involved in this intervention, concerning other fetuses. Moreover, there was the drama concerning the choice of the fetus to be suppressed. Who would have been the unlucky one and why? Some years later, in the psychoanalytical session, Paola was still suffering the loss of the third child never born. During pregnancy, there were threats of abortion from the 5th month. In order to be able to complete the pregnancy until the cesarean section, scheduled 3 weeks before the expiration time, the girl was hospitalized for one month, she was treated with corticosteroid therapy for the growth of fetal lungs and tocolytic therapy to counteract the contractions.

Two healthy children were born: a male and a female that P. nursed for about a year. It was precisely with the breastfeeding that P. managed to compensate that sense of strangeness and detachment that neither the growing womb nor ultrasound images could avoid. Moreover, the Caesarean section had reinforced her feeling of not being suitable for motherhood .

Once P. came back home from the hospital with her babies, the rivalry of the partner exploded. He could not bear to be excluded from P.’s relationship with the children. Few months later the girl, exhausted, decided to move back to her parents’ house.

1. came to therapy because of the separation from her partner, whose relationship had become threatening. The main argument was parenting skills: according to the former partner, P. could not be an adequate mother, because she was not the biological mother of the twins.

The conflict with the former partner and the loss of relationship with him, had strengthened the sense of emptiness of the previous losses. Paula had also a sense of guilt, expressed by doubting  her parenting skills.

Memories of her illness came back together with the cures, the definitive confirmation of the sterility, the frustration for artificial pregnancy and the mourning for those children never born: the explanted embryo and the frozen ones.

With the implantation of the embryos, P. had had her redemption, but the decision to lose one of the three had renewed castration.

For a further investigation, we could ask ourselves the question: how does this maternal experience rebound in P.’s twins? Perhaps the time to answer this question is still premature, because we do not have the clinical material yet and it seems rather fanciful to think that the two fetuses may have recorded the loss of that explanted co-twin in sensory-motor perceptions. On the basis of our clinical material, however, we could hypothesize that the loss experiences have many over-determinations, in relation to the existential events of the subjects. In the investigation of a first trace of loss experience, we could hypothesize that it is engraved in the “cellular memory”, in relation to the failure of sexual reproduction, which happens at each ejaculation for those millions of sperm that die without reaching the egg and for every egg that is not fertilized.

This is N. Peluffo’s suggestive idea:

“Probably, it is the death of 299,999,999 sperm brothers, that forms the first trace of the existence of oneself as a survivor with the consequent sense of guilt. Often these feelings of guilt are bound on brothers or sisters, born and died before the subject, or on the fantasy of a twin which is quickly interpreted as a mental representation of the loss of the placenta. “

© Bruna Marzi, Gioia Marzi

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