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The neonatal ketone body is essential for primordial follicle pool formation and regulates ovarian aging in mice

The neonatal ketone body determines the female ovarian aging via regulating follicle reserve
The working model for the event of ketone bodies in formation of primordial follicle pool. Credit: Xin-Ying Wang et al

Premature ovarian aging (POA) identifies an early on decline in ovarian function; it’s the main reason behind infertility in older women and is seen as a a markedly reduced ovarian reservoir. A fascinating review summarized that women born in famine have a significantly earlier menopausal age, which indicates that the neonatal nutrition condition is essential to find out follicular reserve and age natural menopause. However, the partnership between nutritional conditions during early-life and female reproductive function in adulthood, and also the specific mechanism, is basically unknown.

Scientists from hawaii Key Laboratory for Reproductive Medicine of Nanjing Medical University and Reproductive Medicine Center of Nanjing Drum Tower Hospital discovered that neonatal serum ketone body production could determine the number and quality of the primordial pool by reducing ROS-induced primordial follicle apoptosis during follicular reserve formation in the first life. This study is published in Life Metabolism.

Within an animal model, were subjected to rich dietary lipids from colostrum, which transiently stimulate high expression of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (Hmgcs2), the rate-limiting enzyme generally in most of organs including ovary in neonatal mice. Thus, the neonatal serum ketone body level was significantly greater than adulthood. When Hmgcs2 gene was deleted, the neonatal ketone body level largely decreased, which perfectly mimicked the malnutrition linked to ketone body deficiency in newborn mice. By using this ideal animal model, the researchers discovered that ketone body deficiency in neonatal mice led to smaller ovarian follicle reservoir due to the increased apoptosis of primordial follicles, which further resulted in POA indicated by gradually decreased litter size and prolonged litter interval.

Another challenge the newborns faced was higher oxidative stress due to spontaneous breathing. The ROS production in Hmgcs2 deficient ovary was highly elevated, which resulted in severe DNA damage of primordial follicle, and therefore induced excessive apoptosis of primordial follicles. They further confirmed that -Hydroxybutyrate (-HB), supplementation in Hmgcs2 could reduce ROS production and alleviate DNA damage induced apoptosis of primordial follicle. Thus, the authors demonstrated that the neonatal ketone body could keep up with the quantity and quality of the primordial follicle pool by decreasing ROS production.

In summary, this report elucidates that infant nutrition situation and related neonatal ketone body production play a significant role in the forming of the primordial follicle pool and additional affect the standard ovarian capacity in adulthood. This study offers a new metabolic explanation for POA and new possible ways of enhance the follicular reservoir during early life.



More info: Xin-Ying Wang et al, The neonatal ketone body is essential for primordial follicle pool formation and regulates ovarian ageing in mice, Life Metabolism (2022). DOI: 10.1093/lifemeta/loac017

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Citation: The neonatal ketone body is essential for primordial follicle pool formation and regulates ovarian aging in mice (2022, September 5) retrieved 5 September 2022 from https://medicalxpress.com/news/2022-09-neonatal-ketone-body-important-primordial.html

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