Abstract
Research question
What are the effects of alpha-ketoglutarate (α-KG) treatment on the ovarian morphology
and ovarian reserve function of rats with cyclophosphamide (CTX)-induced premature
ovarian insufficiency (POI)?
Design
Thirty female Sprague Dawley rats were randomly allocated to a control group (n = 10) and a POI group (n = 20). Cyclophosphamide was administered for 2 weeks to induce POI. The POI group
was then divided into two groups: a CTX-POI group (n = 10), administered normal saline, and a CTX-POI + α-KG group (n = 10), administered α-KG 250 mg/kg per day for 21 days. Body mass and fertility was
assessed at the end of the study. Serum samples were collected for hormone concentration
measurement, and biochemical, histopathological, TUNEL, immunohistochemical and glycolytic
pathway analyses were conducted for each group.
Results
The α-KG treatment increased body mass and ovarian index of rats, partially normalized
their disrupted estrous cycles, prevented follicular loss, restored ovarian reserve,
and increased pregnancy rate and litter sizes of rats with POI. It significantly reduced
serum concentration of FSH (P < 0.001), increased that of oestradiol (P<0.001) and reduced apoptosis of granulosa cells (P = 0.0003). Moreover, α-KG increased concentrations of lactate (P = 0.015) and ATP (P = 0.025), reduced that of pyruvate (P<0.001) and increased expression of rate-limiting enzymes of glycolysis in the ovary.
Conclusions
α-KG treatment ameliorates the deleterious effects of CTX on the fertility of female
rats, possibly by reducing the apoptosis of ovarian granulosa cells and restoring
glycolysis.
Keywords
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Biography
Tianlong Li is a postgraduate student at the Institute of Clinical Anatomy and Reproductive Medicine, Department of Histology and Embryology, Hengyang Medical School. He completed standardized resident training at Henan Maternal and Child Health Hospital and obtained the certificate of obstetrics and gynaecology.
Key message
In the cyclophosphamide-induced premature ovarian insufficiency (POI) rat model, alpha-ketoglutaric treatment modifies the effects of cyclophosphamide treatment, possibly by reducing apoptosis and restoring glycolysis. Therefore, the apoptosis of ovarian granulosa cells and the impaired function of glycolysis are worthy of further investigation to determine the pathogenesis of POI.
Article info
Publication history
Published online: January 26, 2023
Accepted:
January 4,
2023
Received in revised form:
December 22,
2022
Received:
July 28,
2022
Declaration: The authors report no financial or commercial conflicts of interest.Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 Published by Elsevier Ltd on behalf of Reproductive Healthcare Ltd.
