Testosterone replacement therapy induces spermatogenesis and partially restores fertility in luteinizing hormone receptor knockout mice.

@article{citeulike:1176623, abstract = {Testosterone (T) is essential for spermatogenesis, fertility, and maintenance of the male phenotype. We analyzed in hypogonadal LH receptor knockout (LuRKO) male mice whether T treatment can restore their phenotype, spermatogenesis, and fertility. In LuRKO mice, spermatogenesis is arrested at round spermatids, adult-type Leydig cells are absent, T production is dramatically decreased, the animals are cryptorchid, and their accessory sex organs are atrophic. T replacement therapy from 21 d of life for 60 or 120 d in LuRKO mice induced a male phenotype macroscopically indistinguishable from that of wild-type littermates as well as full spermatogenesis and testicular descent. Thus, the absence of LH-dependent prepubertal androgen priming is not necessary for subsequent maturation of the male phenotype. Conspicuously, some abnormalities remained in epididymal histology after T treatment despite normal expression of several epididymis-specific genes in caput epididymis. The mice displayed normal mating behavior, although at lower frequency than wild-type controls. The spermatozoa were able to fertilize oocytes, but their impaired passage from epididymis to uterus was apparent. The mice remained subfertile, because only 9\% of all breedings resulted in pregnancy, and only two of 13 mice (15\%) were fertile. Moreover, inflammation in epididymides and prostate was found in many T-treated LuRKO mice, which probably impaired sperm transport and contributed to their high rate of subfertility. In conclusion, T replacement initiated prepubertally only partially restores the fertility of LuRKO mice, even though most features of the male phenotype recover. Full fertility may require higher and/or earlier postnatal T exposure or production of other Leydig cell factors lacking in this model.}, address = {Department of Physiology, Institute of Biomedicine, University of Turku, Finland.}, author = {Pakarainen, T. and Zhang, F. P. and M\"{a}kel\"{a}, S. and Poutanen, M. and Huhtaniemi, I. }, citeulike-article-id = {1176623}, doi = {10.1210/en.2004-0913}, issn = {0013-7227}, journal = {Endocrinology}, keywords = {br\_journal\_club, fertility, knockout\_mouse, lh, spermatogenesis, testosterone}, month = {February}, number = {2}, pages = {596--606}, posted-at = {2007-03-19 21:08:18}, priority = {0}, title = {Testosterone replacement therapy induces spermatogenesis and partially restores fertility in luteinizing hormone receptor knockout mice.}, url = {http://dx.doi.org/10.1210/en.2004-0913}, volume = {146}, year = {2005} }

TY - JOUR ID - citeulike:1176623 L3 - citeulike-article-id:1176623 TI - Testosterone replacement therapy induces spermatogenesis and partially restores fertility in luteinizing hormone receptor knockout mice. JF - Endocrinology VL - 146 IS - 2 SP - 596 EP - 606 AD - Department of Physiology, Institute of Biomedicine, University of Turku, Finland. SN - 0013-7227 N2 - Testosterone (T) is essential for spermatogenesis, fertility, and maintenance of the male phenotype. We analyzed in hypogonadal LH receptor knockout (LuRKO) male mice whether T treatment can restore their phenotype, spermatogenesis, and fertility. In LuRKO mice, spermatogenesis is arrested at round spermatids, adult-type Leydig cells are absent, T production is dramatically decreased, the animals are cryptorchid, and their accessory sex organs are atrophic. T replacement therapy from 21 d of life for 60 or 120 d in LuRKO mice induced a male phenotype macroscopically indistinguishable from that of wild-type littermates as well as full spermatogenesis and testicular descent. Thus, the absence of LH-dependent prepubertal androgen priming is not necessary for subsequent maturation of the male phenotype. Conspicuously, some abnormalities remained in epididymal histology after T treatment despite normal expression of several epididymis-specific genes in caput epididymis. The mice displayed normal mating behavior, although at lower frequency than wild-type controls. The spermatozoa were able to fertilize oocytes, but their impaired passage from epididymis to uterus was apparent. The mice remained subfertile, because only 9% of all breedings resulted in pregnancy, and only two of 13 mice (15%) were fertile. Moreover, inflammation in epididymides and prostate was found in many T-treated LuRKO mice, which probably impaired sperm transport and contributed to their high rate of subfertility. In conclusion, T replacement initiated prepubertally only partially restores the fertility of LuRKO mice, even though most features of the male phenotype recover. Full fertility may require higher and/or earlier postnatal T exposure or production of other Leydig cell factors lacking in this model. KW - br_journal_club KW - fertility KW - knockout_mouse KW - lh KW - spermatogenesis KW - testosterone AU - Pakarainen, T AU - Zhang, FP AU - Mäkelä, S AU - Poutanen, M AU - Huhtaniemi, I PY - 2005/02// UR - http://dx.doi.org/10.1210/en.2004-0913 ER -