# Defining the mechanisms of temperature sensitive meiotic chromosome structures in male infertility

> **NIH NIH K99** · UNIVERSITY OF OREGON · 2022 · $172,476

## Abstract

PROJECT SUMMARY
Sexually reproducing organisms faithfully transmit their genome to the next generation via haploid gametes,
such as eggs and sperm. In contrast to oogenesis and other developmental processes, spermatogenesis must
occur 2-7ºC below basal body temperature. Failure to precisely thermoregulate spermatogenesis or exposure
to elevated temperatures are strongly linked to male infertility and an increased risk of testicular cancer, but the
mechanisms behind temperature induced male infertility and cancer are unknown. Similar to mammals,
Caenorhabditis elegans displays elevated levels of DNA damage and fertility defects in spermatogenesis
following heat exposure. Notably, I have found in C. elegans that the synaptonemal complex (SC), a meiotic
chromosome structure essential for fertility, is altered following heat exposure in only spermatocytes. In
addition, I also uncovered that the SC is sexually dimorphic without heat exposure with spermatogenesis
having differences in both SC protein composition and turnover compared to oogenesis. Here, I hypothesize
that sexual dimorphisms in the SC contribute to the mechanism(s) causing temperature induced male infertility.
In the proposed work, I will exploit the ease to access, manipulate, and visualize both spermatogenesis and
oogenesis in the model system C. elegans to dissect the sexually dimorphic nature of the SC and address how
these sex-specific differences contribute to heat induced male infertility. I will investigate whether differences in
SC organization and composition during spermatogenesis render it temperature sensitive (Aim 1). These
experiments will determine how heat affects both the ultrastructure and dynamics of the SC and other meiotic
chromosome structures during spermatogenesis and oogenesis. In addition, the response of spermatocytes to
heat exposure is variable with nuclei displaying two phenotypes: (1) sensitized nuclei, high levels of DNA
damage and substantial SC defects, and (2) resistant nuclei, significantly less DNA damage and intact SC. To
understand this nucleus autonomous response to heat, I will determine how the transcriptional profiles are
changing within the sensitized and resistant spermatocyte nuclei and assess how loss of the SC influences the
heat stress response of oocytes and spermatocytes (Aim 2). Finally, I will identify and characterize novel
spermatogenesis proteins that cause SC heat sensitivity (Aim 3). Together, this study will illuminate, how
temperature affects genome integrity in spermatocytes and identify the molecular mechanisms that underlie
temperature associated infertility and cancer risk in male reproductive health.

## Key facts

- **NIH application ID:** 10507710
- **Project number:** 1K99HD109505-01
- **Recipient organization:** UNIVERSITY OF OREGON
- **Principal Investigator:** Cori K Cahoon
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $172,476
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10507710

## Citation

> US National Institutes of Health, RePORTER application 10507710, Defining the mechanisms of temperature sensitive meiotic chromosome structures in male infertility (1K99HD109505-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10507710. Licensed CC0.

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