Female mice conceived through the full IVF protocol lost their ovarian reserve earlier
Female mice conceived through the full IVF protocol lost their ovarian reserve earlier
On August 17, the online edition of the Journal of Clinical Investigation published a study of female mice conceived through the full IVF protocol: hormonal stimulation, fertilization outside the body, embryo culture, and transfer into the uterus of a recipient female. At 12 and 39 weeks, these mice had fewer ovarian follicles and lower estradiol levels than naturally conceived mice. Across four consecutive pregnancies, they produced fewer live offspring.
The ovary stores immature eggs in follicles, which are structures that support and nourish an egg as it grows. During early development, the embryo undergoes extensive changes in gene regulation. Previous studies of mice conceived through IVF have reported changes in the placenta, metabolism, and the male reproductive system. The authors examined whether this protocol also affected later ovarian function.
Near the end of fetal development, the ovaries contained the same number of germ cells in both groups. The authors then counted follicles at 12 and 39 weeks. Mice conceived through IVF had fewer follicles at three stages of development. Their ovaries were also smaller relative to body weight, and their blood estradiol levels were lower. The authors interpreted these measurements as evidence that the follicular reserve declined more rapidly after birth.
The differences also affected subsequent pregnancies. The time to conception and the duration of pregnancy were the same in both groups. Females conceived through IVF had more resorbed embryos in the uterus, and they produced fewer live offspring over a series of four pregnancies. The altered condition of the ovaries was therefore associated with poorer outcomes in later pregnancies.
To investigate the cellular basis of these findings, the researchers compared gene activity in the ovaries, eggs, and cumulus cells. Cumulus cells surround the egg and provide nutrients and signals that support its maturation. In these cells, genes involved in energy production, cell division, and chromosome integrity showed altered activity. In the eggs themselves, mitochondria occupied a smaller area, the spindle that distributes chromosomes during cell division was shorter, and the signal indicating oxidative DNA damage was stronger.
In this mouse model, the authors traced a sequence from the early embryonic environment to altered ovarian function, faster depletion of the follicular reserve, and fewer live offspring in subsequent pregnancies.