World's first successful embryo transfer in rhinos paves the way for saving the northern white rhinos from extinction

BioRescue, an international consortium of scientists and conservationists, succeeded in achieving the world's first pregnancy of a rhinoceros after an embryo transfer. The southern white rhino embryo was produced in vitro from collected egg cells and sperm and transferred into a southern white rhino surrogate mother at the Ol Pejeta Conservancy in Kenya on September 24, 2023. The BioRescue team confirmed a pregnancy of 70 days with a well-developed 6.4 cm long male embryo. The successful embryo transfer and pregnancy are a proof of concept and allow to now safely move to the transfer of northern white rhino embryos -- a cornerstone in the mission to save the northern white rhino from extinction.

On September 24, 2023, the BioRescue scientists and veterinarians, led by the Leibniz Institute for Zoo and Wildlife Research (Leibniz-IZW), transferred two southern white rhino embryos into Curra, a southern white rhinoceros, selected as a surrogate mother at the Ol Pejeta Conservancy in Kenya. The oocytes used in producing the embryos were retrieved from Elenore, a southern white rhinoceros living in the Pairi Daiza Zoo in Belgium. The sperm used for fertilisation originated from the male Athos from the Zoo Salzburg in Hellbrunn, Austria. The oocytes from Elenore were fertilised in vitro by intracytoplasmic sperm injection (ICSI) and developed into blastoscysts at Avantea's laboratories in Cremona, Italy. For the embryo transfer in Kenya, the BioRescue scientists transferred two embryos to increase the chance of a successful outcome.

So far, the BioRescue team has performed 13 embryo transfers in rhinoceroses, three in Kenya and ten in Europe. Previously, an embryo transfer, which is a widely used technique in domestic species, has never been attempted in rhinos. BioRescue scientists developed the necessary techniques, by building on decades of their own research.

Currently, there are only two northern white rhinos left in the world: The female Najin and her daughter Fatu. Additionally, living cells from 12 different northern white rhino individuals are stored in liquid nitrogen. The last two females currently live in Kenya, at Ol Pejeta Conservancy, where they are guarded and cared for day and night. Since 2019, the BioRescue conservation science programme produced and cryopreserved 30 northern white rhino embryos. These are currently stored in liquid nitrogen at minus 196 degrees Celsius in Berlin, Germany, and Cremona, Italy, awaiting embryo transfer into southern white rhino surrogate mothers. The successful transfer of a southern white rhino embryo is a proof of concept that allows to take this crucial step -- an embryo transfer with a northern white rhino embryo -- for the first time.

The embryo transfer in this subspecies is entirely new ground as a veterinary and scientific procedure, and all protocols, methods and pieces of equipment had to be newly developed from scratch. As it is the established routine with all BioRescue procedures, the embryo transfers are accompanied by an ethical assessment conducted by Padua University. This was also the case in September, when all participants of the embryo transfer filled out a questionnaire that proposed any possible scenarios during the procedure, and attendant risks to animals and participants.

The vasectomised, sterile teaser bull Ouwan mated with Curra on September 17 and 18, signalling the ideal timing for the embryo transfer, which took place on September 24. After the procedure until November 2023, Curra was monitored on a daily basis in the enclosure at the Ol Pejeta Conservancy. During this period, Ouwan showed no further interest in Curra, a first sign of a successful embryo transfer resulting in pregnancy. The BioRescue team was scheduled for November 28 to perform a pregnancy check in Curra, but the teaser bull Ouwan was found dead on November 22 and Curra was found dead on November 25. Apparently, extremely heavy rains led to a flooding of the surrogate enclosure and set free dormant clostridianbacteria spores. The dissection of the animals revealed a severe systemic infection by a clostridian bacterial strain and resultant intoxication by the bacterial toxin. It also revealed that Curra was pregnant with a 70 days old male fetus that was 6.4 cm long. Tissue samples of the fetus were collected and transported to the Max Delbrück Centre for Molecular Medicine and the Leibniz-IZW in Berlin, Germany. In January 2024, it was confirmed through the analysis of the fetus DNA that the pregnancy resulted from the embryo transfer.

When the BioRescue team arrived in Kenya on November 28, the preliminary results indicated an intoxication with the clostridian bacterial strains Paraclostridium bifermentans and Paenicolostridium sordellii. Immediately after the incident, the BioRescue team, including Kenya Wildlife Service, Wildlife Training Research Institute, Ol Pejeta Conservancy and Safari Park Dvur Králové formed a crisis team on site and established fast and effective measures to protect all current semi-captive rhinos including the last two northern white rhinos Najin and Fatu. The measures included a vaccination programme, quarantine of affected areas and fencing of new emergency enclosures.

The next steps in the BioRescue research programme included the selection and preparation of a new teaser bull. The bull will allow the scientists to know when a possible surrogate female is ready to receive an embryo implantation. The team also has to select the next surrogate mothers. After these steps, which will take several months, an embryo transfer with a northern white rhino embryo will be attempted.

Read more at Science Daily

Mature sperm lack intact mitochondrial DNA

New research provides insight about the bedrock scientific principle that mitochondrial DNA -- the distinct genetic code embedded in the organelle that serves as the powerplant of every cell in the body -- is exclusively passed down by the mother.

The study, a collaboration among Oregon Health & Science University and other institutions, published today in the journal Nature Genetics.

Scientists have long recognized the fact that mitochondrial DNA, or mtDNA, comes exclusively from egg cells in humans, meaning only the mother contributes the genetic code carried by thousands of mitochondria necessary for energy production in every cell in the body.

Previously, it was believed that paternal mtDNA was eliminated soon after a sperm fuses with an oocyte, or developing egg, during fertilization, possibly through an immune-like search-and-destroy response.

However, the study found that while mature sperm do carry a small number of mitochondria, they lack intact mtDNA.

"We found that each sperm cell does bring 100 or so mitochondria as organelles when it fertilizes an egg, but there is no mtDNA in them," said co-author Shoukhrat Mitalipov, Ph.D., director of the Center for Embryonic Cell and Gene Therapy at OHSU.

Researchers found that sperm cells are not only devoid of intact mtDNA, but they also lacked a protein essential for mtDNA maintenance, known as mitochondrial transcription factor A, or TFAM.

Scientists aren't sure why sperm are not allowed to contribute mtDNA, but Mitalipov theorizes that it may relate to the fact that a sperm uses a lot of mitochondrial energy in its biological impetus to fertilize an egg. It would thus accumulate mutations in mtDNA. The developing eggs known as oocytes, by contrast, draw energy primarily from surrounding cells, not from their own mitochondria, so maintain relatively pristine mtDNA.

"Eggs pass on really good mtDNA at least partly because they don't use mitochondria as a source of energy," Mitalipov said.

The 100 or so organelles in sperm are swamped by hundreds of thousands of mitochondria embedded in each egg cell -- each carrying the 37 genes in mitochondrial DNA. The contribution of only maternal mtDNA is believed to confer an evolutionary advantage by limiting the risk of accumulations of mtDNA mutations that cause disease in offspring.

Mitochondria control respiration and energy production within every cell of the body, so mutations in mtDNA can cause a range of potentially fatal disorders affecting organs with high-energy demands, such as the heart, muscle and brain.

To help mothers prevent passing on known mtDNA disorders to their children, Mitalipov pioneered a method called mitochondrial replacement therapy to replace mutant mtDNA through in vitro fertilization using healthy mtDNA from donor eggs.

Congress has prevented the Food and Drug Administration from overseeing clinical trials using the procedure in the U.S., so clinical trials are instead being conducted overseas, including clinical trials in the United Kingdom to prevent disease and in Greece to treat infertility.

Read more at Science Daily

World's oldest animal sperm found in tiny crustaceans trapped in Myanmar amber

 An international collaboration between researchers at Queen Mary University of London and the Chinese Academy of Science in Nanjing has led to the discovery of world's oldest animal sperm inside a tiny crustacean trapped in amber around 100 million years ago in Myanmar.

The research team, led by Dr He Wang of the Chinese Academy of Science in Nanjing, found the sperm in a new species of crustacean they named Myanmarcypris hui. They predict that the animals had sex just before their entrapment in the piece of amber (tree resin), which formed in the Cretaceous period.

Fossilised sperm are exceptionally rare; previously the oldest known examples were only 17 million years old. Myanmarcypris hui is an ostracod, a kind of crustacean that has existed for 500 million years and lives in all kinds of aquatic environments from deep oceans to lakes and rivers. Their fossil shells are common and abundant but finding specimens preserved in ancient amber with their appendages and internal organs intact provides a rare and exciting opportunity to learn more about their evolution.

Professor Dave Horne, Professor of Micropalaeontology at Queen Mary University of London said: "Analyses of fossil ostracod shells are hugely informative about past environments and climates, as well as shedding light on evolutionary puzzles, but exceptional occurrences of fossilised soft parts like this result in remarkable advances in our understanding."

During the Cretaceous period in what is now Myanmar, the ostracods were probably living in a coastal lagoon fringed by trees where they became trapped in a blob of tree resin. The Kachin amber of Myanmar has previously yielded outstanding finds including frogs, snakes and a feathered dinosaur tail. Bo Wang, also of the Chinese Academy of Science in Nanjing added: "Hundreds of new species have been described in the past five years, and many of them have made evolutionary biologists re-consider long-standing hypotheses on how certain lineages developed and how ecological relationships evolved."

The study, published in Royal Society Proceedings B, also has implications for understanding the evolutionary history of an unusual mode of sexual reproduction involving "giant sperm."

The new ostracod finds may be extremely small but in one sense they are giants. Males of most animals (including humans) typically produce tens of millions of really small sperm in very large quantities, but there are exceptions. Some tiny fruit flies (insects) and ostracods (crustaceans) are famous for investing in quality rather than quantity: relatively small numbers of "giant" sperm that are many times longer than the animal itself, a by-product of evolutionary competition for reproductive success. The new discovery is not only by far the oldest example of fossil sperm ever found but also shows that these ostracods had already evolved giant sperm, and specially-adapted organs to transfer them from male to female, 100 million years ago.

Each ostracod is less than a millimetre long. Using X-ray microscopy the team made computer-aided 3-D reconstructions of the ostracods embedded in the amber, revealing incredible detail. "The results were amazing -- not only did we find their tiny appendages to be preserved inside their shells, we could also see their reproductive organs," added He Wang. "But when we identified the sperm inside the female, and knowing the age of the amber, it was one of those special Eureka-moments in a researcher's life."

Wang's team found adult males and females but it was a female specimen that contained the sperm, indicating that it must have had sex shortly before becoming trapped in the amber. The reconstructions also revealed the distinctive muscular sperm pumps and penises (two of each) that male ostracods use to inseminate the females, who store them in bag-like receptacles until eggs are ready to be fertilised.

Such extensive adaptation raises the question of whether reproduction with giant sperms can be an evolutionarily-stable character. "To show that using giant sperms in reproduction is not an extinction-doomed extravagance of evolution, but a serious long-term advantage for the survival of a species, we need to know when they first appeared" says co-author Dr Renate Matzke-Karasz of Ludwig-Maximilians-University in Munich.

Read more at Science Daily