News | ATP's Key Role in Ovulation Revealed, Offering New Hope for Infertility Treatment
A research team led by Associate Professor Naoko Inoue, doctoral student Safiullah Hazim, Associate Professor Yoshihisa Uenoyama, and Professor Hiroko Tsukamura at Nagoya University's Graduate School of Bioagricultural Sciences in Japan found that adenosine triphosphate (ATP), the cell's energy currency, acts as a neurotransmitter during mammalian ovulation. The study showed that ATP triggers ovulation by activating kisspeptin neurons in the brain, a finding that may have applications in treating human infertility and ovulatory disorders in livestock.
How ATP acts in ovulation
During mammalian ovulation, kisspeptin neurons in the anterior hypothalamus serve as the ovulation center. As follicles mature, circulating estrogen levels rise, activating kisspeptin neurons and causing a surge in luteinizing hormone (LH), which triggers ovulation. The team found that the ATP receptor P2RX2 on kisspeptin neurons is crucial to activating this process.
When researchers administered ATP near kisspeptin neurons in the anterior hypothalamus of rats, P2RX2 receptors were activated, causing a large release of LH and ultimately ovulation. Conversely, when a P2RX2-blocking drug was used, the LH surge did not occur despite sufficient estrogen, and ovulation was substantially reduced. In genetically modified rats lacking the kisspeptin gene (Kiss1), ATP also failed to induce an LH surge, further confirming the importance of kisspeptin neurons and their ATP receptors in ovulation.
Source of ATP and neurotransmission
The study also found that rising estrogen levels before ovulation activate purinergic neurons in the brainstem. These neurons release ATP as a neurotransmitter and project near kisspeptin neurons. The team inferred that ATP from brainstem purinergic neurons binds to P2RX2 receptors on kisspeptin neurons and helps trigger ovulation.
Significance and potential applications
“Our study is the first to reveal the role of ATP in inducing ovulation,” Associate Professor Naoko Inoue said. “The finding provides new insight into the regulation of mammalian ovulation and a scientific basis for treating human infertility and ovulatory disorders in livestock.”
Using ATP directly to treat infertility would be challenging because many human cells have ATP receptors. The team proposed an alternative: activating brainstem purinergic neurons to release ATP locally near kisspeptin neurons and indirectly induce ovulation. This strategy may offer a new direction for infertility treatment.
The findings were published in the Journal of Neuroscience.
News | ATP's Key Role in Ovulation Revealed, Offering New Hope for Infertility Treatment
News | ATP's Key Role in Ovulation Revealed, Offering New Hope for Infertility Treatment
A research team led by Associate Professor Naoko Inoue, doctoral student Safiullah Hazim, Associate Professor Yoshihisa Uenoyama, and Professor Hiroko Tsukamura at Nagoya University's Graduate School of Bioagricultural Sciences in Japan found that adenosine triphosphate (ATP), the cell's energy currency, acts as a neurotransmitter during mammalian ovulation. The study showed that ATP triggers ovulation by activating kisspeptin neurons in the brain, a finding that may have applications in treating human infertility and ovulatory disorders in livestock.
How ATP acts in ovulation
During mammalian ovulation, kisspeptin neurons in the anterior hypothalamus serve as the ovulation center. As follicles mature, circulating estrogen levels rise, activating kisspeptin neurons and causing a surge in luteinizing hormone (LH), which triggers ovulation. The team found that the ATP receptor P2RX2 on kisspeptin neurons is crucial to activating this process.
When researchers administered ATP near kisspeptin neurons in the anterior hypothalamus of rats, P2RX2 receptors were activated, causing a large release of LH and ultimately ovulation. Conversely, when a P2RX2-blocking drug was used, the LH surge did not occur despite sufficient estrogen, and ovulation was substantially reduced. In genetically modified rats lacking the kisspeptin gene (Kiss1), ATP also failed to induce an LH surge, further confirming the importance of kisspeptin neurons and their ATP receptors in ovulation.
Source of ATP and neurotransmission
The study also found that rising estrogen levels before ovulation activate purinergic neurons in the brainstem. These neurons release ATP as a neurotransmitter and project near kisspeptin neurons. The team inferred that ATP from brainstem purinergic neurons binds to P2RX2 receptors on kisspeptin neurons and helps trigger ovulation.
Significance and potential applications
“Our study is the first to reveal the role of ATP in inducing ovulation,” Associate Professor Naoko Inoue said. “The finding provides new insight into the regulation of mammalian ovulation and a scientific basis for treating human infertility and ovulatory disorders in livestock.”
Using ATP directly to treat infertility would be challenging because many human cells have ATP receptors. The team proposed an alternative: activating brainstem purinergic neurons to release ATP locally near kisspeptin neurons and indirectly induce ovulation. This strategy may offer a new direction for infertility treatment.
The findings were published in the Journal of Neuroscience.
Source:
Collected online