The influence of cabergoline on the offspring phenotype of human chorionic gonadotropin (hCG) secreting female mice: does mother?s milk make the difference?

RULLI, SUSANA B; CALANDRA, RICARDO S.; MARCIAL LOPEZ, AGUSTINA; RATNER, LAURA D; CAMILLETTI, MARIA ANDREA; DIAZ, GRACIELA; CALANDRA RICARDO S; RULLI, SUSANA B

Mar del Plata

Congreso; LXIV Reunión de la Sociedad Argentina de Investigación Clínica (SAIC); 2019

Sociedad Argentina de Investigación Clínica

Transgenic female mice expressing human chorionic gonadotropin-β (hCGβ+) produce elevated levels of hCG, prolactin and progesterone, show precocious puberty, are infertile and develop pituitary tumors. We have previously demonstrated that a short-term treatment of juvenile hCGβ+ females with the dopamine agonist cabergoline normalizes the phenotypic changes of hCGβ+ females. Even more, the treatment prevented phenotypic alterations on the transgenic offspring. The aim of this study was to determine if the cabergoline treatment has its effect during pregnancy and/or lactation. Two groups of 2-month-old wild-type (WT) females were mated with hCGβ+ males: 1) Six-week-old WT females pretreated with cabergoline (500 µg/kg, ip), every other day for one week (WT-CAB mothers); 2) WT females without treatment (WT- mothers). Offspring from each mother was exchanged at birth and analyzed at three weeks of age. Transgenic offspring from WT-CAB mothers that ingested milk from WT mothers showed phenotypic alterations as exhibited in hCGβ+ females, in terms of vaginal opening and increased uterus weight, as indicators of precocious puberty. On the other hand, the phenotype of transgenic offspring from WT mothers that received milk from WT-CAB mothers was normalized in terms of vaginal opening, uterus weight and ovarian gene expression of Lhcgr, Cyp11a1, Cyp17a1 and Cyp19a1 (qPCR). To analyze if the milk makes the difference, other group of WT females previously mated with hCGβ+ males was treated with cabergoline during lactation from day 1 after birth for one week (0.1 µg/kg ip, every other day). Female transgenic offspring also showed a normalized phenotype at 3 weeks of age. These results suggest that cabergoline has an impact on the offspring during the lactating period and protect them from the phenotypic alterations induced by hCG hypersecretion. The molecular mechanisms involved in this phenomenon remains to be further investigated.