Novel Diurnal Model for In Vitro Fertilization Studies

NIH RePORTER · NIH · K99 · $129,205 · view on reporter.nih.gov ↗

Abstract

Project Summary Light plays a vital role in regulating physiological processes and influences female reproductive success through the circadian system. However, most modern Americans live the majority of their lives indoors where electrical lighting is lower quality than natural light, resulting in exposure to lower intensities of light for an extended duration past sunset, compared to outdoor lighting. Increased reproductive disorders found in nighttime shift workers and seasonal reductions in assisted reproductive technology (ART) success provide compelling evidence that light quality is linked with female fertility. Light exposure comprises various qualities, including photoperiod and intensity, which play a role in resetting circadian rhythms. Although light affects ovarian function in both humans and nocturnal rodents, it remains unclear how these light properties contribute to female reproductive success. Additionally, trace elements (TE), such as zinc, are essential for follicle development, fertilization, and IVF success. Serum TE exhibit circadian variations in humans and nocturnal rats, but the impact of light and circadian variations on TE and female fertility is not well understood. Most research on photic and TE mechanisms that control fertility relies on nocturnal rodents; however, given the opposing in timing in hormone release, ovulation, light responses, and circadian TE levels between nocturnal and diurnal species, this approach leaves a critical gap in our ability to understand how light influences fertility in diurnal species, including humans. I will address this gap by using a diurnal rodent model, the Nile grass rat, to investigate how the hypothalamic-pituitary-ovarian axis adapts to changes in light quality. My preliminary data show that light quality modulates reproduction in grass rats, where long and bright days (LD14:10, 1000 Lux) reduce time to first litter in grass rats compared to standard conditions (LD12:12, 300 Lux). I also show that state-of-the-art laser ablation time-of-flight mass spectrometry (LC-TOF-MS) can be used to generate quantitative maps of TE in the ovary and hypothalamus. These data, coupled with work from my Co-Sponsor validating grass rat superovulation and embryo culture, place me in an excellent position to complete the proposed studies. This proposal will determine how light quality impacts oocyte quality and IVF success (Aim 1), the relationships between circulating TE and ovarian responses in the context of circadian and photic adaptations (Aim 2) and how hypothalamic-pituitary pathways guiding reproduction adapt to light quality (Aim 3). I hypothesize that light quality produces adaptations in hypothalamic circuits guiding female fertility, altering TE distribution, in turn modulating ovarian function and IVF success. These studies will establish a novel diurnal rodent model to provide key insights into the neuroendocrine mechanisms by which light qualities modulate female fertility. The t...

Key facts

NIH application ID
10983856
Project number
1K99HD113843-01A1
Recipient
MICHIGAN STATE UNIVERSITY
Principal Investigator
Alexandra Marie Yaw
Activity code
K99
Funding institute
NIH
Fiscal year
2024
Award amount
$129,205
Award type
1
Project period
2024-08-01 → 2026-07-31