There are just 100 Sumatran rhinos left in the wild in their native lands of Indonesia and Malaysia, and nine are held in captivity for breeding purposes.
The lumbering creatures have dwindled rapidly due to deforestation, humans encroaching on their habitat, and illegal poaching for their horns.
Suci, a nine-year-old female, died on March 30 at the Cincinnati Zoo from an inheritable disease called hemochromatosis, in which too much iron builds up in the body.
Her mother also died of the condition when she was 21, said Terri Roth, vice president of conservation at the Cincinnati Zoo.
"It is just an absolutely huge blow. I just can't tell you how terrible I feel about it," Roth told AFP.
Last year, Roth stirred controversy by announcing the zoo would attempt to breed Suci with her younger brother, Harapan, since there were no other available mates.
Female rhinos can develop tumors and cysts in their reproductive tract if they do not become pregnant when they come of age, making it impossible for them to bear offspring in later years.
But efforts to breed the pair never took place, Roth said. Zoo officials first realized something was awry with Suci in October, and though she experienced a period of improvement, her condition deteriorated again rapidly.
Word of Suci's passing was followed by more bad news about Iman, a female rhino recently captured in Malaysia and transferred to the Tabin Wildlife Reserve on March 21.
Conservationists believed she might have been pregnant when they found her, given her "feisty behavior, a torn ear, probably a result of a past tussle with a male, (and) a mass with blood vessels inside the uterus," said a statement from the reserve.
However, an ultrasound examination done under anesthesia dashed those hopes.
"There is no fetus in her uterus but big, big tumors, some as big as footballs," said Thomas Hildebrand of the Leibniz Institute for Zoo and Wildlife Research (IZW) Berlin.
The discovery suggests that she had not mated in at least five years, and that Sumatran rhinos, which need a lot of space and isolation from humans, may no longer be reproducing on their own.
"This is grim news as this seems to confirm our thoughts that rhinos might not be breeding any more in the wild," said Sen Nathan, assistant director at the Sabah Wildlife Department.
Some experts think capturing more rhinos from the wild could bolster breeding efforts, even though in-vitro fertilization has not worked, at least not yet, in Sumatran rhinos.
"If we want to save the species, we need to bring rhinos into managed conditions and try out advanced reproductive technologies," said Zainal Zahari Zainuddin, a Borneo Rhino Alliance veterinarian based at the Tabin Wildlife Reserve.
The Cincinnati Zoo was the first facility to successfully breed the Sumatran rhino in 112 years and Suci was one of three calves born there.
The Sumatran Rhino Sanctuary in Indonesia has also produced a calf in captivity.
Roth said at least two of the rhinos in Indonesian captivity are fertile, and they have a capable male who was sent by the Cincinnati zoo.
"Hopefully we will be able to continue working with our Indonesian colleagues and help them succeed in producing some more calves in the future," said Roth.
Meanwhile, US zoo officials have to decide what is next for Suci's brother Harapan, the only remaining Sumatran rhino in US captivity.
"Is it important to have an ambassador animal here in the US? Or would it be more important for him to go back to southeast Asia and have an opportunity to breed?
"We will need to sit down and put our heads together and do what's best," said Roth.
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