# The neural control of thermoregulatory changes accompanying pregnancy

> **NIH NIH K00** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $89,470

## Abstract

DESCRIPTION (provided by applicant): Most neurological and neurodevelopmental disorders are 
sex-biased in incidence or severity. To understand why one sex may be vulnerable to a disease, it is 
important to understand brain development in both sexes. Mood, cognition, and other processes are 
regulated by estrogen receptor (ER) α neurons. Female have increased number of ERα neurons in the 
hypothalamus, compared to males. This is an example of a sex difference in neurochemical phenotype, 
the most common type of sex difference in the brain. Despite this, little is known on the mechanisms 
controlling their development. Our research suggests that epigenetic mechanisms underlie sex 
differences in neurochemical phenotype that may contribute to sex biases in disease. Inhibiting DNA 
methylation in the brains of newborn mice reduces sex differences in ERα in the preoptic area (POA) 
and the ventrolateral area of the ventromedial hypothalamus (VMHvl) at weaning. We recently reported 
that DNA methyltransferases (Dnmts; which add methyl marks) and ten eleven translocases (Tets; 
which remove methyl marks), peak shortly after birth in both sexes in the hypothalamus. Additionally, 
females have higher expression of Dnmts, while males have higher expression of Tets during this 
period. This suggests that DNA methylation and hydroxymethylation are dynamic and sex- biased 
during neonatal brain development. Interestingly, both sexes have an equally high number of ERα cells 
in the VMHvl at birth, but only in males, it decreases 50% by weaning. This proposal will test the 
hypothesis that ERα cells in males, but not females, accumulate DNA methylation marks during 
postnatal development which establishes the sex difference. The F99 phase will test 1) whether subpopulations of ERα cells with functional roles are sensitive to neonatal inhibition of DNA methylation 
using single-molecule fluorescent in situ hybridization and 2) whether specific sub-populations downregulate ERα expression across development (Aim 2a). Lastly, using methylated and 
hydroxymethylated DNA immunoprecipitation sequencing, it will test the hypotheses that there are 
global sex differences and developmental changes in the epigenome, and specifically, that the ERα
promoter in males has increased levels of DNA methylation compared to females (Aim 2b). The 
proposed study will help the candidate, Laura Cortes, achieve her goal of becoming a tenure-track 
professor at an R1 institution. This proposal will provide training in cutting-edge techniques, such as 
sm-FISH and epigenomic sequencing, to investigate how DNA methylation regulates neurochemical 
phenotype in both sexes. The Neuroscience Institute at Georgia State University is an ideal 
environment given the 1) access to the expertise of reputed neuroendocrinologists and state-of-the-art 
tools, 2) collaborative intra-departmental and inter-institutional atmosphere, and 3) the plethora of 
career development opportunities. Completio...

## Key facts

- **NIH application ID:** 10767181
- **Project number:** 5K00HD109205-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Laura Cortes
- **Activity code:** K00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $89,470
- **Award type:** 5
- **Project period:** 2022-02-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10767181

## Citation

> US National Institutes of Health, RePORTER application 10767181, The neural control of thermoregulatory changes accompanying pregnancy (5K00HD109205-04). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10767181. Licensed CC0.

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