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Hum. Reprod. Advance Access originally published online on June 30, 2006
Human Reproduction 2006 21(10):2514-2520; doi:10.1093/humrep/del093
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© The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Metoclopramide-induced hyperprolactinaemia caused marked decline in pinopodes and pregnancy rates in mice

Michele Quarante Panzan1,*, José Maria Soares Júnior1,*, Eduardo Leme Alves da Motta1, Edna Freymuller Haapalainen2, Manuel de Jesus Simões2, Heloisa Allegro Baptista3, Mauro Abi Haidar1 and Edmund C. Baracat1,4

1 Department of Gynecology 2 Department of Morphology 3 CEDEME, The Federal University of São Paulo, São Paulo, Brazil

4 To whom correspondence should be addressed at: Rua Dr. Diogo de Faria, 1087 Cj 610 V. Clementino, São Paulo, SP 04037-003, Brazil. E-mail: baracat.gineco{at}epm.br

* Both authors contributed equally to this study.

BACKGROUND: The impact of hyperprolactinaemia on endometrial function, along with embryo implantation, has been the subject of discussion. This article examines whether experimental hyperprolactinaemia can affect mouse ovarian function, endometrial pinopodes and embryo implantation. METHODS: For pinopode analysis, 60 female mice were randomly divided into two groups: control (vehicle) and experimental [metoclopramide (MCP) 200 µg per day]. Injections were given subcutaneously for 50 days, and then, normally cycling females were housed with male mice for copulation during proestrus. The animals were killed on the fifth day following coitus when the antimesometrium portions of the uterine horns were removed for endometrial analysis. Blood was collected for prolactin (PRL) determination. In the second experiment, 60 female mice were used to evaluate the ovarian function by measuring estrogen and progesterone levels and counting luteal bodies and oocytes in the oviduct and uterus during estrus. RESULTS: The highest pregnancy rates and the largest population of pinopodes were both found in the vehicle group (P < 0.01). Estrogen and progesterone levels in MCP-treated mice were lower than those in control mice (P < 0.05). Also, the number of implantations was significantly lower in the MCP-treated group compared with the vehicle group after embryo transfer (P < 0.001). CONCLUSION: PRL seems to have suppressive effects on ovarian function and the number of pinopodes; conceivably, hyperprolactinaemia has a negative effect on mouse embryo implantation.

Key words: embryo implantation/hyperprolactinaemia/metoclopramide/mice/pinopodes


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