The role of seasonal changes in light on the reproductive axis in female mice

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Project Summary In humans and laboratory rodents, there are seasonal patterns in birth and offspring mortality rates, reproductive hormone release, and in vitro fertilization success. It is unknown how female fertility is responding to time-of- year in non-seasonal breeders. Seasonal changes in lighting are characterized by high intensity long summer days and low intensity short winter days. Seasonal changes in light quality, notably light duration (photoperiod) and intensity, are candidate variables to drive the time-of year changes in female reproduction of non-seasonal breeders. As human and non-seasonal laboratory rodents do not exhibit breeding restricted to specific times of year, potential mechanisms by which variations in light quality, specifically photoperiod or light intensity, may modulate hormone release and ovarian function are unexamined. Photoperiod is the most salient and well- established cue signaling seasonal changes. However, with extensive artificial lighting, many modern-day humans do not experience seasonal changes in photoperiod, but do experience seasonal changes in light intensity. By increasing our understanding of how seasonally-modulated breeders adapt their physiology to light conditions, this project will lay the foundation necessary for the development of therapeutic interventions to improve reproduction during times of year when fertility and reproductive success are decreased. To demonstrate that the reproductive axis is modulated by photoperiod in non-seasonal mice, I established a longitudinal experimental protocol to collect serial blood samples from diestrus females on LD12:12 and long days (LD19:5) with indoor lighting intensity (300 Lux). I found that females on LD19:5 have reduced pulsatile release of luteinizing hormone (LH) and follicle stimulating hormone (FSH), two hormones required for ovarian function and fertility. The most direct pathway by which light influences LH and FSH is via a neuronal population expressing vasoactive intestinal peptide (VIP) of the suprachiasmatic nucleus. Light enters the eye and is transmitted to VIP neurons that project to gonadotropin releasing hormone (GnRH) neurons to modulate LH and FSH. Based on these data, I hypothesize that the VIP-GnRH-pituitary pathway adapts to changes in photoperiod and light intensity, with reduced functionality of this circuit on long days (LD19:5) and in bright intensity (1000 Lux) light, leading to reduced LH and FSH release patterns and reduced ovarian function compared to short (LD5:19) days and dim (50 lux) light. Aim 1 will determine the degree by which light intensity and photoperiod induce changes in LH and FSH release and ovarian function. Aim 2 will determine how VIP-GnRH-Pituitary connectivity and function adapt to photoperiod and light intensity. These studies will provide key insights into the neuronal mechanisms by which light qualities modulate hypothalamic and downstream endocrine pathways. The training from this proposal, with guidance from my Sponsors and mentoring committee, will prepare me for a successful career as an academic researcher investigating the role of light in modulating reproductive success.