Journal
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
Volume 241, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ecoenv.2022.113723
Keywords
Circadian rhythm; Constitutional delay of growth and puberty (CDGP); Female; Gonadal hormones; Ovary; Hypothalamus
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Funding
- Southwest Medical University Program [2021ZKMS036]
- National Natural Science Foundation of China [82170523]
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This study investigated the effects of chronic circadian disturbance (CCD) during fetal stage on the pubertal development of female mice. The results showed that CCD exposure led to delayed puberty in female mice, characterized by lower body weight, decreased hormone levels, and altered gene expression in the ovary and hypothalamus. Additionally, disrupted expression of genes associated with fatty acid metabolism and circadian clock was observed in the ovaries of these mice.
Constitutional delay of growth and puberty (CDGP) refers to the late onset of puberty. CDGP is associated with poor psychosocial outcomes and elevated risk of cardiovascular and osteoporotic diseases, especially in women. The environmental factors that contribute to CDGP are poorly understood. Here, we investigated the effects of chronic circadian disturbance (CCD) during the fetal stage on the pubertal development of female mice. Compared to non-stressed female (NS-F) mice that were not exposed to CCD in utero, adolescent CCD female (CCD-F) mice exhibited phenotypes that were consistent with CDGP, including lower body weight, reduced levels of circulating gonadal hormones, decreased expression of gonadal hormones and steroid synthesis-related enzymes in the ovary and hypothalamus, irregular estrus cycles, and tardive vaginal intmitus initial opening (VO) days (equivalent to the menarche). Phenotypic differences in the above-noted parameters were not observed in CCD-F mice once they had reached adulthood. The expression of genes involved in fatty acid metabolism was perturbed in the ovary and hypothalamus of CCD-F mice. In addition, the ovaries of these animals exhibited altered diurnal expression profiles of circadian clock genes. Together, our findings not only suggest that CCD during fetal development may result in delayed puberty in female mice, they also offer insights on potential mechanisms that underlie CDGP.
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