A1 Refereed original research article in a scientific journal
Maternal dopamine agonist treatment before pregnancy reverses infertility and hyperprolactinemia in hCG-overexpressing mice through lactation: Evidence of generational effects
Authors: Ratner, Laura D.; Lopez, Agustina Marcial; Giorgio, Noelia P. Di; Poutanen, Matti; Huhtaniemi, Ilpo; Rulli, Susana B.
Publisher: Elsevier BV
Publishing place: CLARE
Publication year: 2025
Journal: Molecular and Cellular Endocrinology
Journal name in source: Molecular and Cellular Endocrinology
Journal acronym: MOL CELL ENDOCRINOL
Article number: 112538
Volume: 602
Number of pages: 10
ISSN: 0303-7207
eISSN: 1872-8057
DOI: https://doi.org/10.1016/j.mce.2025.112538
Web address : https://doi.org/10.1016/j.mce.2025.112538
Dopamine agonists, such as cabergoline (Cab), have demonstrated efficacy in restoring reproductive function in cases of hyperprolactinemia and hormonal dysregulation. This study investigates the long-term consequences of maternal Cab treatment on the reproductive phenotype of the progeny in a female transgenic (TG) mouse model with hyperprolactinemia and infertility due to human chorionic gonadotropin (hCG) beta-subunit overexpression. The TG females that received Cab between weeks 3-4 of life exhibited a reversion of hyperprolactinemia and infertility, whereas WT females retained their fertility. When TG-cab-or WT-Cab-treated females were crossed with WT or TG males, respectively, their female TG offspring showed a reversal of precocious puberty, regularization of estrous cycles, fertility, and prevention of hyperprolactinemia and prolactinomas. Despite the persistent high LH/hCG bioactivity, the normalization of prolactin levels led to a reduction in ovarian luteinization markers and progesterone levels. The TG female pups born to either WT-cab-or TG-cab-treated females exhibited a normalized phenotype, thus suggesting that the effects were indeed due to maternal Cab administration, and not to the transgene. Cross-fostering experiments showed that the long-lasting programming effect of maternal Cab on offspring occurred during lactation because the TG female pups from non-treated WT female/ TG male pregnancies, but nursed by Cab-treated females, were free from the altered TG phenotype. These results suggest that Cab treatment before pregnancy may have a multigenerational effect on the hypothalamic-pituitary-gonadal axis of the offspring, mediated during lactation. This highlights potential implications for generational health and clinical practices regarding the use of dopamine agonists during lactation.
Funding information in the publication:
This study was supported by a grant from CONICET (PIP082), Rene Barón, Williams, and Felipe Fiorellino Foundations from Argentina.
