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The Human Fetal Testis Is a Site of Expression of Neurotrophins and Their Receptors: Regulation of the Germ Cell and Peritubular Cell Population

Medical Research Council Human Reproductive Sciences Unit, Centre for Reproductive Biology, Edinburgh EH16 4SB, United Kingdom

Address all correspondence to: Dr. R. A. Anderson, Medical Research Council Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Chancellor’s Building, Little France Crescent, Edinburgh EH16 4SB, United Kingdom. E-mail: r.a.anderson{at}hrsu.mrc.ac.uk.

In the fetal testis, organization of the tissue into two compartments consisting of cords containing Sertoli and germ cells surrounded by peritubular cells and of other cells within the interstitium is essential for subsequent function. Neurotrophins (NTs) act as survival and differentiation factors in the nervous system and have been detected in the developing rodent testis. Expression of mRNA for nerve growth factor; NTs 3 and 4 and brain-derived neurotrophic factor; the high-affinity receptors TrkA, TrkB, and TrkC; and the low-affinity p75 receptor were detected in the human testis between 14 and 19 wk gestation. NT4 mRNA and protein were predominantly localized to the peritubular cells. These cells were also the site of expression of p75. By contrast, nerve growth factor and NT3 were mainly expressed in Sertoli and interstitial cells. Treatment of testis organ cultures with the Trk-specific kinase inhibitor K252a resulted in a marked decrease in both gonocyte and peritubular cell number and proliferation with little effect on Sertoli cells. These data demonstrate the expression of NTs and their receptors in the human fetal testis during the second trimester and indicate possible roles in the regulation of proliferation and survival of germ cells and peritubular cells.

Abbreviations: BDNF, Brain-derived neurotrophic factor; BrdU, bromodeoxyuridine; ER, estrogen receptor; HRP, horseradish peroxidase; NGF, nerve growth factor; NRS, normal rabbit serum; NT, neurotrophin; SSC, sodium saline citrate; TBS, Tris-buffered saline; Trk, high-affinity tyrosine kinase.

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