Hidden source of genetic diversity found in human sperm

Amazing stuff!

"... Scientists have identified an unexpected source of genetic variation in human sperm that occurs earlier in sperm development than previously thought. ...

researchers ... found that one type of genetic recombination involving the chromosomes, called non-crossover gene conversion, happens before the cell divisions that produce sperm.

The findings suggest that genetic recombination events in sperm happen in two stages, both before and after cell division. The team found that these DNA recombination patterns can vary between individuals, including between identical twins. This study opens new opportunities to investigate biological mechanisms underlying fertility, genome evolution and inherited disease. ..."

From the abstract:

"Meiotic recombination is a fundamental process that generates genetic diversity by creating new combinations of existing alleles. Whereas crossovers in humans are well characterized, the more frequent non-crossovers that lead to gene conversion remain challenging to study.

Here we show that single high-fidelity long sequencing reads from sperm can capture both crossovers and non-crossovers, which enables effectively arbitrary sample sizes for analysis from a single male.

We analysed 2,382 candidate non-crossovers in 15 sperm samples from 13 donors, and identified a consistent component with properties distinct from PRDM9-induced recombination.

This phenomenon was not associated with meiotic double-strand break sites identified by DMC1 binding, the crossover recombination map or GC-biased gene conversion, but was associated with genomic fragile sites.

This component is also seen in paternal non-crossover gene conversions in pedigree data.

Applying the same analysis to 12 blood samples, we observed non-crossover gene conversions with similar properties, but very few crossover events.

Further, we demonstrate variation between donors for the different types of recombination, even when they share the same PRDM9 genotype.

We suggest that a substantial fraction of the non-crossover gene conversion events seen in sperm arise prior to meiosis."

Hidden source of genetic diversity found in human sperm "New research provides a detailed view of how genetic diversity is generated in sperm and opens new opportunities to investigate the biological mechanisms underlying fertility, genome evolution, and inherited disease."

Long-read sequencing reveals pre-meiotic gene conversion in sperm (open access)

Fig. 1: Detecting recombinant reads in sperm samples.

Fig. 4: Origins of meiotic and pre-meiotic recombination events in the male germline.

Scientists made human egg cells from skin cells

Amazing stuff! This could be a breakthrough since cloning of Dolly the sheep in 1996. 

When will the first human baby be born from an artificial womb outside a woman's body? I bet it could happen within the next 10-20 years.

The Oregon based researchers could not resist to mention "... this method would allow for the possibility of same-sex couples to have a child genetically related to both partners ..."

"Creating human eggs from adult cells just got one step closer to reality.

A technique used in cloning combined with fertilization and a bit of chemical coaxing caused human skin cells to produce eggs able to give rise to early human embryos ...

The effort is the latest attempt to make eggs and sperm from human cells. Researchers have already succeeded in making these important cell types from many types of animals, including pandas. But producing human eggs and sperm has proven elusive. ..."

From the abstract:

"Somatic cell nuclear transfer (SCNT) enables the direct reprogramming of somatic cells into functional oocytes, albeit with a diploid genome.

To address ploidy reduction, we investigated an experimental reductive cell division process, termed mitomeiosis, wherein non-replicated (2n2c) somatic genomes are prematurely forced to divide following transplantation into the metaphase cytoplasm of enucleated human oocytes.

However, despite fertilization with sperm, SCNT oocytes remained arrested at the metaphase stage, indicating activation failure.

Artificial activation using a selective cyclin-dependent kinase inhibitor successfully bypassed this arrest, inducing the segregation of somatic chromosomes into a zygotic pronucleus and a polar body.

Comprehensive chromosome tracing via sequencing revealed that homologous chromosome segregation occurred randomly and without crossover recombination. Nonetheless, an average of 23 somatic chromosomes were retained within the zygote, demonstrating the feasibility of experimentally halving the diploid chromosome set.

Fertilized human SCNT oocytes progressed through normal embryonic cell divisions, ultimately developing into embryos with integrated somatic and sperm-derived chromosomes. While our study demonstrates the potential of mitomeiosis for in vitro gametogenesis, at this stage it remains just a proof of concept and further research is required to ensure efficacy and safety before future clinical applications."

Scientists made human egg cells from skin cells

OHSU researchers develop functional eggs from human skin cells (original news release)

Induction of experimental cell division to generate cells with reduced chromosome ploidy (open access)

Fig. 1: Ploidy reduction by mitomeiosis.

Researchers develop world's first test-tube testicles

Amazing stuff! Homunculus is coming closer one organoid at a time!

"The world’s first test-tube testes have been created by a group of researchers at Bar-Ilan University, signaling a huge advancement in several key fields of research such as fetal sex determination, male infertility solutions, and strategic conversation starters to get yourself excused from the Thanksgiving dinner table. ..."

"... are testis organoids – tiny, artificial organs produced from real mouse testis. Development of organoids has greatly advanced in the last decade with the realization that two-dimensional cellular sample in vitro cannot mimic the behavior of an entire organ. Today, organoids of the brain, kidneys, intestines, and other organs have already been produced. The testicular organoids created by Gonen's group closely simulate a natural testicle. ..."

From the abstract:

"The testis is responsible for sperm production and androgen synthesis. Abnormalities in testis development and function lead to disorders of sex development and male infertility. Currently, no in vitro system exists for modelling the testis. Here, we generated testis organoids from neonatal mouse primary testicular cells using transwell inserts and show that these organoids generate tubule-like structures and cellular organization resembling that of the in vivo testis. Gene expression analysis of organoids demonstrates a profile that recapitulates that observed in in vivo testis. Embryonic testicular cells, but not adult testicular cells are also capable of forming organoids. These organoids can be maintained in culture for 8-9 weeks and shows signs of entry into meiosis. We further developed defined media compositions that promote the immature versus mature Sertoli cell and Leydig cell states, enabling organoid maturation in vitro. These testis organoids are a promising model system for basic research of testes development and function, with translational applications for elucidation and treatment of developmental sex disorders and infertility."

Researchers develop world's first test-tube testicles  - ISRAEL21c The petri dish privates mark a milestone in the study of sexual development disorder and male infertility research.

Bar-Ilan University researchers produce “laboratory testicles” The artificial testicles will contribute to the advancement of research in male fertility and sexual development disorders, and are expected to facilitate the eventual production of sperm in the laboratory

Towards a “Testis in a Dish”: Generation of Mouse Testicular Organoids that Recapitulate Testis Structure and Expression Profiles (open access)

Caption: A bright field image of a testicular organoid created from mouse embryos and incubated in a dish for 14 days. The tubular structures formed in the dish are clearly visible. 

Graphical abstract

Sperm or egg from any cell? It's called IVG and it holds huge promise and peril

Recommendable! A challenging revolution in human reproduction is on its way! Perhaps, a few more years!

Some humans will likely fear humans are playing God! However, it is God who enabled us to make this progress!

The article also contains a few serious warnings!

"... National Academies of Sciences, Engineering and Medicine .... is opening an unprecedented gathering: It's titled "In-Vitro Derived Human Gametes as a Reproductive Technology."

It's the academy's first workshop to explore in-vitro gametogenesis, or IVG, which involves custom-making human eggs and sperm in the laboratory from any cell in a person's body. ...
Japanese scientists describe how they've already perfected IVG in mice. The researchers used cells from the tails of adult mice to create induced pluripotent stem (iPS) cells, and then coaxed those iPS cells to become mouse sperm and eggs. They've even used those sperm and eggs to make embryos and implanted the embryos into the wombs of female mice, which gave birth to apparently healthy mouse pups. ...
[researchers] turned human blood cells into iPS cells, and used those iPS cells to create very primitive human eggs. Others have created primitive human sperm this way. ...
IVG would enable infertile women and men to have children with their own DNA instead of genes from the sperm and eggs or donors.
Same goes for women of any age, rendering the biological clock irrelevant. ...
IVG could also enable gay and trans couples to have babies that are genetically related to both partners. ...
Another theoretical possibility is "solo IVG" — single people having "uni-babies" — babies with just one person's genes ..."

Sperm or egg from any cell? It's called IVG and it holds huge promise and peril : Shots - Health News : NPR

Credits: Human Progress Weekly Links