How can a disease increase the likelihood of stillbirth in male infants?

Question

In the ancient world, maternity death rates were very high due to lack of medical knowledge and understanding, as well as life-saving technologies. As such, it was a toss up to whether the woman and baby would both survive the process. In this world, maternal death rates are almost unheard of, with all the risk of dying being transferred to the child and sparing the mother. However, the number of males in a population has been on a decline in recent decades. This is because of the rapid increase of male infants being born dead. The resulting gender imbalance as led to females far exceeding males within society, which has caused a shift in the power dynamic within the Empire and has forced it to rethink many of its internal structures for how society is run. Marriages would occur between sister-wives, who would share a man between them. This form of marriage would take the form of a collection of woman-woman unions, with the male serving as the legal partner. These unions between females wouldn't be sexual, but a pragmatic and stable way to produce heirs. These unions would take place between two or more women, but be limited to one husband to prevent conflict between families over reproductive rights.

Due to a lack of biological knowledge, this has been rationalized in terms of the accepted religion. A man's strength and fortitude is tested even before birth, and only the strongest of will survive the process and earn the right to be born into the world. However, the reality is that a mysterious genetic disease has spread to all corners of the world, and has been carried down through the female line. This disease has left girl infants unscathed and unaffected, but has led to the decline in the male population. The disease has stabilized at the present time, infant males have a 50% percent chance of being stillborn.

How could a disease like this work where it would only affect male infants but leave female infants unharmed?

Answer 1

Ever heard of Wolbachia?

It is an intracellular parasite of many arthropods. One of the ways in which it spreads is to infest the ovaries of infected females, so all eggs that female produces carry wolbachia. Sperm cells aren't suitable for carrying the bacterium, and so the infection acts to minimize (but not eliminate) the number of male offspring ensuring the maximum number of infected grand-children.

To summarise the wikipedia summary,

• Male killing occurs when infected males die during larval development, which increases the rate of born, infected females.
• Feminization results in infected males that develop as females or infertile pseudofemales.
• Some scientists have suggested that parthenogenesis may always be attributable to the effects of Wolbachia (presumably you'd rather skip this option)
• Cytoplasmic incompatibility is the inability of Wolbachia-infected males to successfully reproduce with uninfected females.

The infection doesn't necessarily have any other consequences. It is also possible for species to become dependent on Wolbachia to reproduce, for various reasons... this means that any attempt to eliminate the bacterium via antibiotics might cause the host to die or be rendered infertile (and this is used as a biological control measure for some pest species in real life).

Obviously, this specific bacterium couldn't work on humans as-is, and has had an extremely long time to co-evolve with arthropods so as to get its present-day arsenal of tricks. A novel infection of humans is unlikely to achieve the same thing in a short period of time, but it isn't so implausible that it couldn't be handwaved in. Perhaps other mammal species were infected first and the sex-ratio effects became prominent there, and the disease crossed the species barrier in the same way as one of our other modern zoonoses.

Answer 2

A retrovirus is a virus that inserts its own genes into the hosts chromosomes. This is usually not done at random, with the viral genes latching on to specific parts of the host DNA through mechanisms that we still don't fully understand.

It might be that you have a virus that latches on to the Y chromosome's non-combining region. This virus would spread only among genetic males. If it leaves people already born unaffected, but has a very high mortality and lethality rates among fetuses, then this would explain the condition you describe. Since a single man can usually impregnate a lot of females, this wouldn't kill off humanity in very short time - though over long spans this will reduce genetic variation among the species, which would kill off humanity in a dozens of thousands of years to millions of years.

Answer 3

Two genes, two inherited genetic diseases.

For the image there are 2 genes: the red / pink one is autosomal recessive. Because it is on the X chromosomes males have one copy; females have 2. Dark red is autosomal recessive and lethal and birth. The blue one is a pseudoautosome. Dark blue is recessive and lethal early in development.

For the red gene, it is a standard X linked genetic syndrome. An analogous situtaton is Fragile X syndrome.

https://medlineplus.gov/genetics/condition/fragile-x-syndrome/#inheritance

Fragile X syndrome is inherited in an X-linked dominant pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. (The Y chromosome is the other sex chromosome.) The inheritance is dominant if one copy of the altered gene in each cell is sufficient to cause the condition. X-linked dominant means that in females (who have two X chromosomes), a mutation in one of the two copies of a gene in each cell is sufficient to cause the disorder. In males (who have only one X chromosome), a mutation in the only copy of a gene in each cell causes the disorder.

Thus half the males are stillborn because half get the dark red version.

It is tricky because in this scenario there can be only heterozygote females. There cannot be a female homozygous for red because 1: she would be stillborn and 2: there are no fathers with the red gene to pass on. But a mother with 2 pink genes will not be affected and so their sons are not at risk.

This is where the second gene comes in. Enter the pseudoautosome.

---

There are only heterozygote females because of a second deleterious gene. This gene is on both the X and y chromosomes in the pseudoautosomal region.

https://en.wikipedia.org/wiki/Pseudoautosomal_region

The pseudoautosomal regions, PAR1, PAR2,1 are homologous sequences of nucleotides on the X and Y chromosomes.

The pseudoautosomal regions get their name because any genes within them (so far at least 29 have been found for humans)2 are inherited just like any autosomal genes. PAR1 comprises 2.6 Mbp of the short-arm tips of both X and Y chromosomes in humans and great apes (X and Y are 155 Mbp and 59 Mbp in total). PAR2 is at the tips of the long arms, spanning 320 kbp Normal male mammals have two copies of these genes: one in the pseudoautosomal region of their Y chromosome, the other in the corresponding portion of their X chromosome. Normal females also possess two copies of pseudoautosomal genes, as each of their two X chromosomes contains a pseudoautosomal region.

The dark blue deleterious gene is on the X chromosome with the pink nondeleterious gene. We will say they are linked and so unlikely to be split apart during meiotic recombination. If a zygote has 2 copies of dark blue it will cease to develop; not stillborn but miscarries at a very early stage.

The Y chromosome has a light blue nondeleterious copy and so males are not affected by this issue.

Evolution can eventually save this population when an X chromosome recombines and there is a girl born with X that has both light pink and light blue. It may take a while.

Answer 4

The disease causes the body of the woman to strongly reacts to testosterone production. Normally this would not be an issue in a woman's body, unless she is pregnant of a male.

When the fetus starts producing testosterone to proceed with the sexual differentiation, it also triggers an antigenic reaction from the mother's body, and since the mother also provides antibodies to the fetus, those antibodies will attack the fetus itself, resulting in a 50% chance of the fetus being killed in the process.