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A Role for Tachykinins in Female Mouse and Rat Reproductive Function¹

Centro de Producción y Experimentación Animal,³ Universidad de Sevilla, Sevilla, Spain Instituto de Investigaciones Químicas,⁴ Centro de Investigaciones Científicas Isla de la Cartuja, 41092 Sevilla, Spain Department of Anaesthetics, University of Melbourne and Department of Obstetrics and Gynaecology,⁵ Royal Women's Hospital, Carlton, Victoria 3053, Australia Area de Farmacología,⁶ Departamento de Medicina, Universidad de Oviedo, Oviedo, Spain Animalario Universitario,⁷ Universidad de Oviedo, Oviedo, Spain

Tachykinins may be involved in reproduction. A reverse transcription-polymerase chain reaction assay was used to analyze the expression of tachykinins and tachykinin receptors in different types of reproductive cells from mice. The preprotachykinin (PPT) genes, PPT-A, PPT-B and PPT-C, that encode substance P/neurokinin A, neurokinin B, and hemokinin-1, respectively, and the genes that encode the tachykinin NK₁, NK₂, and NK₃ receptors were all expressed, at different levels, in the uterus of superovulated, unfertilized mice. The mRNA of neprilysin (NEP), the main enzyme involved in tachykinin metabolism, was also expressed in the uterus. Isolated cumulus granulosa cells expressed PPT-A, PPT-B, PPT-C, and NEP and low levels of the tachykinin NK₁ and NK₂ receptors. Mouse oocytes expressed PPT-A and -B mRNA transcripts. A low expression of the three tachykinin receptors was observed but PPT-C and NEP were undetectable. Two- and 8- to 16-cell mouse embryos expressed only a low-abundance transcript corresponding to the NK₁ receptor. However, the mRNAs of PPT-B, PPT-C and NEP appeared in blastocyst-stage embryos. A low-abundance transcript corresponding to the NK₂ receptor was the only target gene detected in mice sperm. Female mice or rats treated neonatally with capsaicin showed a reduced fertility. A reduction in litter size was observed in female rats treated in vivo with the tachykinin NK₃ receptor antagonist SR 142801. These data show that tachykinins of both neuronal and nonneuronal origin are differentially expressed in various types of reproductive cells and may play a role in female reproductive function.

¹ This work was supported by grants from Ministerio de Ciencia y Tecnología (SAF2002-04080-C02-01 and PB-MED01-15), Spain. C.O.P. and F.M.P. contributed equally to this work.

² Correspondence: M.L. Candenas, Instituto de Investigaciones Químicas, Avenida Americo Vespucio, s/n, Isla de la Cartuja, 41092 Sevilla, Spain. Fax: 34954460565; mluz{at}cica.es

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