ABSTRACT
Emx2 deletion impairs the growth and maintenance of the genital ridge. However, its role in subsequent germ cell differentiation during embryonic stages is unknown. Using a tamoxifen-inducible Cre-loxP mouse model (Emx2(flox/flox), Cre-ER(TM), hereafter called as Emx2 knockdown), we showed that germ cell differentiation was impaired in Emx2-knockdown testes. Representative characteristics of male germ cell differentiation, including a reduced ability to form embryonic germ (EG) cell colonies in vitro, down-regulation of pluripotency markers and G1/G0 arrest, did not occur in Emx2-knockdown testes. Furthermore, FGF9 and NODAL signalling occurred at abnormally high levels in Emx2-knockdown testes. Both blocking FGF9 signalling with SU5402 and inhibiting NODAL signalling with SB431542 allowed germ cells from Emx2-knockdown testes to differentiate in vitro Therefore, EMX2 in somatic cells is required to trigger germ cell differentiation in XY foetuses, posterior to its previously reported role in the growth and maintenance of the genital ridge.
Subject(s)
Cell Differentiation , Fibroblast Growth Factor 9/metabolism , Germ Cells/cytology , Homeodomain Proteins/physiology , Nodal Protein/metabolism , Pluripotent Stem Cells/cytology , Testis/cytology , Transcription Factors/physiology , Animals , Cell Proliferation , Fibroblast Growth Factor 9/genetics , Gene Expression Regulation, Developmental , Germ Cells/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Nodal Protein/genetics , Pluripotent Stem Cells/metabolism , Testis/metabolismABSTRACT
<p><b>OBJECTIVE</b>To study the influence of the reference values for semen analysis proposed in the 5th edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen on the indication spectrum for intrauterine insemination (IUI).</p><p><b>METHODS</b>We retrospectively analyzed the clinical data of 111 cycles of IUI by the reference values for semen analysis in the 4th edition of the WHO Laboratory Manual (group A) and 84 cycles by the 5th edition (group B). We recorded and compared the percentages of various indications for IUI between the two groups.</p><p><b>RESULTS</b>The complications for IUI in groups A and B were as follows: asthenospermia (87.4% [97/111] vs 55.9% [47/84], P < 0.05), oligospermia (0 vs 0), teratospermia (51.4% [57/111] vs 35.7% [30/84]) , abnormal liquefaction (0.9% [1/111] vs O) , sexual dysfunction and genital malformation (0 vs 3.6% [3/84] , immune infertility (0.9% [ 1/111] vs O), and unexplained infertility (3.6% [4/111] vs 2. 4% [2/84 ] ). There were no significant differences between the two groups in the percentages of all the indications except that of asthenospermia.</p><p><b>CONCLUSION</b>The reference values for semen analysis proposed in the 5th edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen have an evident influence on the indication spectrum for IUI by largely reducing the cases of IUI for male factors, prolonging the cycles of some patients, causing excessive diagnosis and treatment for females, and increasing their mental and economic burdens.</p>
