Synchronization of ovulation with mating improves fertilization in ‘hyperovulatory’ mice

Hyperovulation is an advanced technique that greatly increases the number of eggs produced by female mice. However, existing hyperovulation techniques have a low fertilization rate, likely caused by the low frequency of sperm reaching the female’s eggs in vivo. Now, a team of researchers from Japan has found that mating hyperovulatory mice with their partner during or after ovulation can overcome this limitation and improve fertilization rates.

Mice are an integral part of experiments in various research fields, including biotechnology and medical science. Since maintaining a reproductive strain of mice is essential in most cases, increasing the litter size of these animals is eagerly sought. Female mice produce about eight to ten oocytes during ovulation. Usually, all oocytes ovulated from the ovaries are fertilized during mating, resulting in a similar number of offspring. Now, while scientists have invented techniques to greatly increase the number of ovulated eggs, these “superovulation” techniques fail to produce a similarly large number of fertilized eggs.

In a study recently published in PLOS ONE Feb 6, 2023 Researchers from Japan have shown that timing ovulation and mating can increase the fertilization rate in hyperventilated mice. In the study led by Satohiro Nakao and Kotono Ito of Kumamoto University, the researchers divided the mice into three groups based on the timing of their ovulation – before ovulation, during ovulation and after ovulation.

Mating female mice with their breeding pair during or after ovulation resulted in a significantly higher number of fertilized oocytes than when they were housed together before ovulation. Professor Toru Takeo, the paper’s corresponding author, who is also affiliated with Kumamoto University, noted that “the number of embryos obtained after ovulation was three times higher than that obtained before ovulation.”

Hyperovulation is induced in female mice by injection of equine chorionic gonadotropin and human chorionic gonadotropin (hCG). It results in the production of about 20 eggs and a similar number of fertilized eggs. The researchers involved in this study had previously discovered an improved technique for hyperovulation in mice that uses installin antiserum and equine chorionic gonadotropin. While this technique, called “hyperovulation,” resulted in the release of more than 100 oocytes from ovulating mice each cycle, the number of fertilized oocytes remained around 20.

The team hypothesized that the low fertilization rate was caused by the low number of sperm reaching the egg in the ampulla, the area of ​​the fallopian tube where fertilization normally occurs. Although millions of sperm reach the uterus during mating, only a small percentage swim far enough to reach the ampulla. This can be corrected by timing the mating of the mice. According to Professor Takeo, “The results of this study suggest that a sufficient number of sperm reach the ampulla to fertilize the oocyte when ovulation and mating are synchronized.”

The timing of ovulation induced by hyperovulation techniques has been precisely determined. In the study, mice in the “preovulatory” group were mated 0 to 10 hours, the “during ovulation” group were mated 10 to 15 hours, and the “postovulatory” group were mated 15 to 19 hours after receiving hCG. injection.

The underlying physiological mechanism responsible for the threefold increase in fertilization rate demonstrated in the study is not clear. However, Professor Takeo notes, “The timing of ovulation and accumulation may support sperm to enter the fallopian tube and achieve fertilization by driving the flow of ovarian fluid, although further studies are needed to confirm this phenomenon.”

The study’s findings have several potential practical implications. As mentioned earlier, a method to increase the reproductive capacity of genetically modified mice that are widely used in scientific research can be extremely beneficial. In addition, the results may help improve infertility treatments in humans.