Metoclopramide-induced hyperprolactinemia during pregnancy and lactating alters chondrocyte proliferation and apoptosis in the murine femoral and tibial epiphyseal growth plate.

STUDY

DESIGN

Experimental study about hyperprolactinemia on the Epiphyseal Growth Plate (EGP).

OBJECTIVES

Evaluated the EGP of the lactating female with hyperprolactinemia induced by metoclopramide and of the physiological lactating female.

METHODS

Ten (10) females received 0.2 mL of saline solution at 0.9% (control group, CTR), and ten (10) females received 200 µg/day of metoclopramide (experimental, HPRL). Treatments lasted for 79 consecutive days (50 days of induction of HPRL, 19 days of gestation, and 10 days of breastfeeding). On the 79th day, the lactating female mice were euthanized and the knees were removed and fixed in 10% formaldehyde for 24 hours and decalcified bone for immuno-histochemistry (TUNEL and Ki67) analysis, and use Masson's trichrome. Data were statistically analyzed by the Mann-Whitney test (p < 0.05).

RESULTS

Apoptosis of chondrocytes was higher in the EGP (femur and tibiae) of the lactating female-HPRL compared to the EGP (femur and tibiae) of the lactating female-CTR (p < 0.05). Cell proliferation of chondrocytes was significantly higher in the EGP in the femur compared to the EGP in the femur of lactating females-CTR (p < 0.05), however, the EGP in the tibiae (HPRL vs. CTR) was not significant, p > 0.05.

CONCLUSIONS

The present study revealed excess cell death (TUNEL) of chondrocytes, consisting of 2-fold in the EGP of the femur and 4-fold in the EGP of the tibiae of a lactating female with hyperprolactinemia induced by metoclopramide, with greater involvement of the tibiae in relation to the femur, which is a fact that can lead to an imbalance between chondrogenesis and osteogenesis.