The Effect of Clomiphene Citrate and Letrozole in Apoptotic Pathways and Cell Cycle in Human Primary Cumulus Cells and the Protective Effect of Estradiol.
Reprod Sci
; 29(8): 2272-2281, 2022 08.
Article
em En
| MEDLINE
| ID: mdl-35513593
ABSTRACT
Clomiphene citrate (CC) and letrozole are ovulatory stimulants that, despite high ovulation rates, achieve low pregnancy rates. This study aimed to investigate the in vitro effects of CC and letrozole, alone or in combination with estradiol, on apoptosis in human cumulus cells. We performed a controlled prospective study using primary cumulus cell cultures from patients undergoing in vitro fertilization (n=22). Alpha-inhibin immunocytochemistry was used to assess cell culture purity and morphology. Cell viability was evaluated by MTT assay, cell cycle status by flow cytometry, and Caspase-3, Bax and SOD-2, and S26 gene expression by qPCR. Cells were treated for 24 hours in 5 conditioned media CC, CC + estradiol, letrozole, letrozole + estradiol and control. None of the treatments affected cell viability, but letrozole reduced the mean percentage of cells in the S phase compared to control (24.79 versus 21.70, p=0.0014). Clomiphene treatment increased mRNA expression of Bax (4 fold) and SOD-2 (2 fold), which was reversed by co-treatment with estradiol. SOD-2 expression increased in cells treated with letrozole compared to control (4 fold), which was also reversed by estradiol. These findings suggest that clomiphene citrate and letrozole do not significantly affect the viability of human cumulus cells. Still, the expression of genes involved in apoptosis was modulated by these drugs alone and in association with estradiol, suggesting that CC and letrozole may have direct effects on cumulus cells beyond their known mechanisms of action.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fármacos para a Fertilidade Feminina
/
Infertilidade Feminina
Tipo de estudo:
Clinical_trials
/
Observational_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
/
Pregnancy
Idioma:
En
Revista:
Reprod Sci
Assunto da revista:
MEDICINA REPRODUTIVA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA