#gametes

The publishing of academic papers denying biological reality isn't slowing down; in fact, it's much worse.

This new one, titled Sex-Associated Variables: A Framework for Neurotoxicology, was just published in Neurotoxicology, a very serious academic journal.

The abstract says, "The phrase 'sex differences'" creates a, quote, "distinct binary," and that "this binary is reductive at best" because, according to them, "sex is a spectrum containing a mosaic of factors," "an amalgamation of contributing factors that are grouped together," and "a conglomeration of variables."

This is the same tired claim we've seen again and again, that males and females are not real and discrete biological categories but rather they exist on a spectrum of maleness and femaleness. The categories are continuous, or a mosaic, or a complicated collection of chromosomes, hormones, anatomy, behaviors, and other traits.

The problem with this argument is actually very simple. It's totally self-refuting and I'll explain why. You see, the authors want to break sex down into what they call Sex-Associated Variables or SAVs. These include morphological variables like breasts and facial hair and genitalia, genetic variables like chromosomes and the SRY gene, and then endocrine variables like testosterone and estrogen.

Now, there's nothing wrong with studying those variables, but the fact that these "sex-associated" variables aren't binary doesn't mean that sex itself isn't binary. It just means the two sexes differ in a lot of ways, and that many of those differences vary continuously, or they overlap. Everybody already knows this. Nobody thinks that sex differences in height, for instance, are binary, with all men being one height and all women being another, shorter height. We all understand that sex differences in height refer to group averages, and this is true for most sex differences.

So here's where the new paper totally collapses under its own logic. The authors spend the entire paper discussing what they call "sex-associated traits," so traits that are associated with being male or being female. They talk about male and female hormonal profiles, male and female sex chromosomes, male and female genital anatomy, and even sex differences in various non-human animal species.

But how do they know, how does anybody know, which traits are associated with males and which traits are associated with females? I want you to really think about that. You can't say that XY chromosomes are associated with being male unless you already know what a male is independently of XY chromosomes. Similarly, you can't say that breast development is associated with females unless you already know what a female is independently of having breasts. And you can't say that higher testosterone is associated with being male in humans unless the category male has already been defined independently of hormone levels.

And what is it that all these "sex-associated traits" are associated with? The answer is having the biological function to produce either sperm or ova. That's it.

This becomes especially obvious when the authors bring up male and female zebrafish in the paper because zebrafish don't have sex chromosomes like humans do, yet nobody is confused about whether zebrafish have males and females and which individuals are which. But why is that? Because male and female are not defined by sex chromosomes. They're not defined by SRY genes or hormone levels. They are defined by the type of gamete an organism has the biological function to produce. This is true across all species that reproduce by fusing an egg and sperm, including species with radically different sex determination systems, endocrine systems, and morphology.

The upstream mechanisms of sex determination vary widely in nature, and the downstream consequences of sex are also very diverse. But what makes an individual male or female does not vary. It's all about gametes.

The paper also uses a figure with a color scheme that's a little suspicious, to say the least, and makes me think that there might be some hidden agenda behind their arguments Maybe it's just a coincidence, but given that the paper repeatedly frames the sex binary as inadequate for transgender, non-binary, or gender-diverse people, individuals whose sex is in no way ambiguous, mind you, it certainly appears like the science is being made to serve a certain political narrative.

And that's, I think, where the real problem actually is. The authors are taking something true and important, the idea that doctors and researchers should pay attention to individual differences, and using it to smuggle in the false notion that males and females are merely social constructs arbitrarily overlaid on continuous variation.

But medicine already understands and accounts for individual variation. A doctor can know a patient's sex while also knowing that hormone levels can vary, that DSDs exist, and that not all men and women respond the same to drugs or toxicants.

The binary nature of sex does not erase or ignore any of this variation; it organizes it. And unfortunately, because this paper is published in a relatively high-impact journal, it will probably be cited over and over again by activists, advocacy groups, journalists, and even lawyers as evidence that science says sex is a spectrum; it's not.

For a deeper breakdown of all the ways that activists and activist academics try to distort the basic biological reality of the sexes, read my paper, Why There Are Exactly Two Sexes, in the journal Archives of Sexual Behavior. It walks through the common arguments that rely on chromosomes, DSDs, spectrum models, polythetic models, and even multilevel models and explains why every attempt to get around gametes ends up relying on them anyway.

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page 248 - that was great. Still buzzing. Sober buzz. Like a bee! Unless bees get high on their honey. I am high on my honey.

Woah boy. Got it bad.

So.

None of you thought it might be important to tell me that ferns have sperm that swim??? I just had to find all this out on my own?

And, (apparently, & no one thought to bring this up either🙄) fern plants are only one form… they have this 'other form' (tiny, ephemeral, difficult to find in the wild) alternates generations-- Fern spores don't grow into ferns! (WHAT) they grow into 'gemetophytes' (WHAT) THEN you get a fern.

"Scientists have created mice with two biological fathers by generating eggs from male cells, a development that opens up radical new possibilities for reproduction.

The advance could ultimately pave the way for treatments for severe forms of infertility, as well as raising the tantalising prospect of same-sex couples being able to have a biological child together in the future.

“This is the first case of making robust mammal oocytes [a.k.a. egg cells] from male cells,” said Katsuhiko Hayashi, who led the work at Kyushu University in Japan and is internationally renowned as a pioneer in the field of lab-grown eggs and sperm.

Hayashi, who presented the development at the Third International Summit on Human Genome Editing at the Francis Crick Institute in London on Wednesday, predicts that it will be technically possible to create a viable human egg from a male skin cell within a decade. Others suggested this timeline was optimistic given that scientists are yet to create viable lab-grown human eggs from female cells.

Previously scientists have created mice that technically had two biological fathers through a chain of elaborate steps, including genetic engineering. However, this is the first time viable eggs have been cultivated from male cells and marks a significant advance. Hayashi’s team is now attempting to replicate this achievement with human cells, although there would be significant hurdles for the use of lab-grown eggs for clinical purposes, including establishing their safety.

“Purely in terms of technology, it will be possible [in humans] even in 10 years,” he said, adding that he personally would be in favour of the technology being used clinically to allow two men to have a baby if it were shown to be safe.

“I don’t know whether they’ll be available for reproduction,” he said. “That is not a question just for the scientific programme, but also for [society].”

The technique could also be applied to treat severe forms of infertility, including women with Turner’s syndrome, in whom one copy of the X chromosome is missing or partly missing, and Hayashi said this application was the primary motivation for the research.

Others suggested that it could prove challenging to translate the technique to human cells. Human cells require much longer periods of cultivation to produce a mature egg, which can increase the risk of cells acquiring unwanted genetic changes.

Prof George Daley, the dean of Harvard Medical School, described the work as “fascinating”, but added that other research had indicated that creating lab-grown gametes from human cells was more challenging than for mouse cells. “We still don’t understand enough of the unique biology of human gametogenesis to reproduce Hayashi’s provocative work in mice,” he said.

Study Methods

The study, which has been submitted for publication in a leading journal, relied on a sequence of intricate steps to transform a skin cell, carrying the male XY chromosome combination, into an egg, with the female XX version.

Male skin cells were reprogrammed into a stem cell-like state to create so-called induced pluripotent stem (iPS) cells. The Y-chromosome of these cells was then deleted and replaced by an X chromosome “borrowed” from another cell to produce iPS cells with two identical X chromosomes.

“The trick of this, the biggest trick, is the duplication of the X chromosome,” said Hayashi. “We really tried to establish a system to duplicate the X chromosome.”

Finally, the cells were cultivated in an ovary organoid, a culture system designed to replicate the conditions inside a mouse ovary. When the eggs were fertilised with normal sperm, the scientists obtained about 600 embryos, which were implanted into surrogate mice, resulting in the birth of seven mouse pups. The efficiency of about 1% was lower [although not THAT much lower] than the efficiency achieved with normal female-derived eggs, where about 5% of embryos went on to produce a live birth.

The baby mice appeared healthy, had a normal lifespan, and went on to have offspring as adults. “They look OK, they look to be growing normally, they become fathers,” said Hayashi.

Going Further

He and colleagues are now attempting to replicate the creation of lab-grown eggs using human cells.

Prof Amander Clark, who works on lab-grown gametes at the University of California Los Angeles, said that translating the work into human cells would be a “huge leap”, because scientists are yet to create lab-grown human eggs from female cells.

Scientists have created the precursors of human eggs, but until now the cells have stopped developing before the point of meiosis, a critical step of cell division that is required in the development of mature eggs and sperm. “We’re poised at this bottleneck at the moment,” she said. “The next steps are an engineering challenge. But getting through that could be 10 years or 20 years.”

The X Factor

We have 23 pairs of chromosomes, but our gametes, sperm and eggs, only carry one copy of each. To achieve that, precursors called germ cells undergo a form of cell division known as meiosis: in this artificial ovary, lab-grown female germ cells are shown in purple, with those undergoing meiosis in yellow, and supporting cells in cyan. Meiosis has added complications for females, who possess two copies of the X chromosome. To avoid producing a harmful excess of X-linked proteins, one copy of X is inactivated in every cell, but it needs to be re-activated in germ cells. Researchers tracking the status of X chromosomes in cultured mouse cells found that this cycle of inactivation and re-activation is hugely important for efficient meiosis. This could help explain why producing immature eggs, or oocytes, in the laboratory is so difficult; improvements to the process would ultimately benefit research on female fertility.

Written by Emmanuelle Briolat

Image from work by Jacqueline Severino and colleagues

Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain

Image originally published with a Creative Commons Attribution-NonCommercial 2.0 Generic (CC BY-NC 2.0)

Research published in The EMBO Journal, May 2022

Non-intersex males and females can be infertile, we know their sex because of the type of gonadal tissue they have, either ovarian or testicular exclusively.

For intersex people with exclusively streak gonads and no testicular or ovarian tissue, they are female.