# Circular RNA Role in Ovarian Follicular Development and Fertility

> **NIH NIH R21** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2024 · $232,500

## Abstract

Project Summary
Ovarian follicles undergo a series of dynamic changes following the ovulatory surge of luteinizing hormone
including cumulus expansion, oocyte maturation, ovulation and luteinization. Post-transcriptional gene
regulatory events are critical for mediating LH follicular responses and among all non-ribosomal RNA isoforms,
circular RNA (circRNA) are the most abundantly expressed form of RNA, yet remain the least studied.
Functionally, circRNA can act as miRNA sponges, protein sponges/decoys, regulators of transcription and
translation. The role of circRNA in context to ovarian follicular development is relatively unknown, although
their presence is known and our recent RNA sequencing studies of ovarian granulosa cells before and after the
LH surge indicates the significant upregulation of circRNA, some of which have probable roles in preovulatory
follicular development. Uniquely, KHDRBS1 (KH RNA Binding Domain Containing, Signal Transduction
Associated 1) RNA element binding sites were identified in a large proportion of these LH-induced circRNA
granulosa cell transcripts. KHDRBS1 is a recognized RNA binding protein with circRNA biogenic activity in
other tissues and our preliminary results indicate high expression in ovarian granulosa cells. Moreover, global
Khdrbs1 knockout female mice were reported to be severely sub-fertile. In this proposal, we will test the
hypothesis that KHDRBS1 is a key regulator of LH induced circRNA biogenesis and of periovulatory events
associated with ovulation. To investigate this hypothesis the following aims are proposed 1) Examine effect
granulosa cell-specific KHDRBS1 loss has on LH-regulated circRNA biogenesis and fertility and 2)
Examine LH-regulated circRNA molecular mechanism(s) of action and their functional impact on
periovulatory follicular events. Aim 1 will use a granulosa cell-specific Khdrbs1 knockout mice (Khdrbs1fl/fl
:Aromatase cre) female mice to address the role of this protein in circRNA biogenesis and its impact on fertility.
In Aim 2, a complete functional analysis of several LH-regulated circRNA will be completed, to elucidate their
mechanisms of action and whether these unique RNA molecules have roles in LH mediated events such as
cumulus expansion, oocyte maturation, ovulation and luteinization. Studies in other systems indicate that
circRNA are important modulators of cell differentiation and abnormal expression of circRNA has been
associated with female reproductive diseases (i.e., primary ovarian insufficiency and polycystic ovarian
syndrome).

## Key facts

- **NIH application ID:** 10811437
- **Project number:** 1R21HD110932-01A1
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** LANE K. CHRISTENSON
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $232,500
- **Award type:** 1
- **Project period:** 2024-08-22 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10811437

## Citation

> US National Institutes of Health, RePORTER application 10811437, Circular RNA Role in Ovarian Follicular Development and Fertility (1R21HD110932-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10811437. Licensed CC0.

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