Dual-Gender Macrochimerism

I stumbled across this paper:

The title is certainly interesting, even it if it’s watered down by the “predicted to be” meaning it’s mostly well grounded speculation. It’s doubly interesting if you’re a narcissistic trans woman on the search for the underlying biological mechanism responsible for making your life more annoying than necessary.

So what is it all about, and how is it connected to gender dysphoria? To understand the paper we have to understand genetic chimerism. Chimerism is when an organism is composed of cells with two or more distinct genotypes. Microchimerism is when small amounts of cells in an organism have different genotypes from the host. The most common occurrence of microchimerism is fetomaternal microchimerism. Fetomaternal microchimerism occurs during pregnancy, when small amounts of the baby’s cells will cross the placenta and take residence in the mother’s body (and vice versa). Prevalence of these cells decrease with age, but have been found even 27 years postpartum.

Macrochimerism is a whole other ball game. The most common cause of macrochimerism is when a two zygotes merge. This can result in entire organs being of a different genotype from each other. This can occur with different zygotes with differently sexed chromosomes as well. One of the most interesting cases of this is hermaphroditism (intersex), where an individual has both sets of genitalia and/or reproductive organs. Most cases of macrochimerism are not so obvious. Typically they are subtle, harmless, and go unnoticed unless the person has their DNA tested. This makes it difficult to determine the true rate of macrochimerism.

This brings us back to Brian Hanley’s paper. He correctly points out that dual-gender macrochimerism exists, and other forms of non-visible macrochimerism exist. Therefore it is likely there are non-obvious dual-gender macrochimeras, in which other, non sexual, tissues are affected. In Brian’s words:

…the existence of human macrochimeras in which large proportions of cells are male and female is predicted to have a correlation with homosexuality and transgender self-identification because in many such cases, the central nervous system, or crucial parts of it, will be of one sex and the gonads and body form will be of the opposite sex.

So far so good, but the paper is mostly speculation. Brian hazards a guess at the true rate of macrochimerism but admits he is probably off by “orders of magnitude.” He provides a framework for the sort of longitudinal study that would be necessary to properly study the prevalence of macrochimeras, but I don’t see them happening anytime soon I won’t hold my breath.

Genotype vs. Hormones

The most interesting part of Brian’s paper was the assertion that the sex of the nervous system is as important, if not more important contributor to gendered behavior than the hormonal environment the system developed in.

This surprised me because I have first hand experience that hormones change the way one thinks and feels. I would have guessed that brain development was guided by the hormonal environment it was soaking in, which in turn was dictated by the chromosomes of the gonads. This is not without scientific support. For example, gendered personality traits seems to be effected by pre-natal exposure to androgens, and I believe there are some studies on homosexuality and transsexuality that find correlations as well.

Brian references three studies in support of this assertion:

Bilateral Brained Finches

This paper discusses a species of finch with gender differentiable brains. One difference is that the males have a stronger “song circuit” in their brains that causes them, but not the females, to sing a courtship song. There is some evidence that hormonal environment affects brain development in these finches. Female finches exposed to estradiol develop a song circuit similar to males and sing the courtship song. However these finches did not exhibit completely sex reversed behavior, and males with testicular hormonal blockers still develop the song circuit. This suggests that both hormones and sex chromosomes are important for gendered neural development.

Conveniently, a rare gynandromorphic bilateral brained finch was found, with a nearly symmetric split between male and female. You can see the bilateral split in the plumage.

Bilateral Gynandromorphic Finch

One side (B) has male plumage, the other side (C) female plumage. The researchers found the finch had a masculinized right hemisphere and much less masculinized, and partially feminized left hemisphere. This provides evidence that the effect chromosomes of nervous tissue are not over powered by the developmental or current hormonal environment.

To be honest, and this is definitely talking out of my depth, the experiment didn’t seem as conclusive on the brain differences as the other anatomical differences. Although the “song circuit” was larger on the right (male) side of the brain, there were issues comparing the size to the controls, which would have proved insightful.

Quail

In contrast to the finches, these quail brain chimeras had to be built, not found. Japanese quails have a male organized brain by default that is thought to be de-masculinized by estrogen, transforming it into a female organized brain. Fortunately, this differentiation happens after the brain starts to appear during gestation. This allows crazy people researchers to graft cross-sex forebrain primordium, causing the birds to develop cross-sexed brains.

Male-forebrained, female host quails showed typical female quail behaviors, including sexual behavior. This is congruent with the idea that estrogen (prevalent in female quails) demasculinizes the transplanted forebrain, reorganizing it to be more feminine. A point for the hormonal basis for gendered brain differences.

Female-forebrained, male host quails are a different case. They exhibited reduced male behaviors, and reduced to non-existant male sexual behaviors. In addition, sexually dimorphic brain features such as the medial preoptic nucleus were found to be feminized despite being raised in a male hormonal environment. A point for the genotype basis for gendered brain differences.

I would be interested to know if gay Japanese quails exist, and if they do, what their typical behaviors are so they can be compared to the cross-sexed quails. I know it’s a faux pas to conflate sex with sexuality, but given their ontological proximity and extremely high rates of correlation I would be surprised if the biological mechanisms weren’t intertwined in some fashion.

People

Birds are great (#bavi) but what about people? Do we have any questionably ethical studies where we manipulate the hormonal, anatomical or genetic components of humans that might give us some insight?

Yes, yes we do!

In 1975 there was a study that followed the development of males born with abnormally small, or missing penises. Since they were too small to function, doctors removed them, essentially performing infant GRS. The “men” were raised as girls from birth, complete with HRT and raised as girls since birth.

From the abstract:

Forty-five cases of genetic males were assigned and habilitated as females, 43 because of a congenitally defective penis (micropenis with or without hypo- spadias], and two because of infantile ablatio penis. One of the latter has an identical twin brother as a control. Now 9 years old, she has differentiated a female gender identity in marked contrast to the male gender identity of her brother. Some of the other patients are now adolescent or adult in age. They demonstrate that the twin can expect to be feminine in erotic expression and sexual life. Maintained on estrogen therapy, she will have normal feminine physique and a sexually attractive appearance. She will be able to establish motherhood by adoption.

I guess that settles the debate, hormonal and social environment trump genetics.

Now, if you’re like me, you might notice that 9 is a bit young to be drawing conclusions. Pre-pubescent humans still have some significant phase of development from which the brain is not exempt. For instance, gendered personality differences don’t manifest until after puberty, indicating that there is significant differentiation that takes place during puberty.

Fortunately someone did a follow up study  and found that the child in question transitioned to male after puberty and has been comfortably living as one since. A similar study found that 8 out of 14 males assigned girls at birth (for similar reasons) ended up identifying as males by puberty and 6/14 even transitioned physically. The 2 other males with the same condition were raised as males and decided to remain as males. Although the sample size is smöl, gender dysphoria and transition are sufficiently rare that this high rate of transition is shocking and convincing.

Conclusion

So what did we learn? I learned that performing infant GRS should probably be halted until we have more research. I also learned that human brain development is not what that I thought is was.

My new model of gendered brain differences:

  1. Gonads develop according to gonadal chromosomes
  2. Different gonads produce different sex hormones
  3. This hormonal environment informs the organization of tissue, including the brain
  4. Brains that develop in a male hormonal environment are organizationally male and vice versa.
  5. Brains are organized, and thus gendered differentiated, due to genotypical and hormonal factors.

A lot more (expensive, time consuming) research needs to be done. I am convinced that the “sex” of human nervous tissue is a significant determinant in human gendered behavior and identification and that dual-gender macrochimerism is a plausible biological mechanism behind the transgender phenomenon.

Self Destruction Anthem

Self Destruction Anthem by Days N Daze is a fun song to sing along to. It’s probably a blast if you have similarly disillusioned friends to belt alongside of. I wouldn’t know. I don’t have friends.

It consists of two, roughly 14 syllable lyrics about self destructive behavior, followed by “Why do I do this? Whyyyyyyyy? Why do I do this to myself?” and occasionally interspersed with “I’m self destructing. No one can save me. You asked me if I loved you I said maybe. Why would you love me? You should learn to hate me. I’m going not where fast.” Repeat until you can’t sing any more.

In the spirit of things, I made my own personal version of the lyrics. One day I’ll learn to play the guitar, make my father proud, and then disappoint him as I strum out of tune to overly indulgent self loathing.

Lyrics

My name is Amy and I can’t keep going on this way,
I’m scared of life, I stay at home and sleep away the day.

Why do I do this? Whyyy? Why do I do this to myself?

Each day I get the shakes at what life has in store,
I think I’m living properly, sleeping alone on my hard floor.

Why do I do this? Whyyy? Why do I do this to myself?

I’m self destructing. No one can save me. You asked me if I loved you, I said maybe. How could you love me? You should learn to hate me. I’m going nowhere fast.

I go to my job everyday, I’d rather break a bone,
I sit in subtle agony and then pass out home alone.

Why do I do this? Whyyy? Why do I do this to myself?

I haven’t given up on life but it feels like life gave up on me,
If you told it’s a bit of both I wouldn’t disagree.

Why do I do this? Whyyy? Why do I do this to myself?

All I’ve done for years on end is too much LSD,
It’s not great but being sober seems much worse to me.

Why do I do this? Whyyy? Why do I do this to myself?

I’m self destructing. No one can save me. You asked me if I loved you, I said maybe. How could you love me? You should learn to hate me. I’m going nowhere fast.