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转基因小鼠中 Mullerian 抑制物质缺乏会干扰生后生殖细胞发育:隐睾症不孕理解的线索。

Mullerian-inhibiting substance deficiency in transgenic mice interferes with postnatal germ cell development: clues for understanding infertility in cryptorchidism.

机构信息

Department of Paediatrics, University of Melbourne, Australia.

出版信息

J Pediatr Surg. 2009 Dec;44(12):2335-8. doi: 10.1016/j.jpedsurg.2009.07.058.

DOI:10.1016/j.jpedsurg.2009.07.058
PMID:20006021
Abstract

AIM

Mullerian-inhibiting substance (MIS) may have a role in postnatal germ cell development, although this remains unproven. Elucidating the regulatory factors is crucial in finding new treatments for preventing infertility in cryptorchidism. We studied germ cell development in neonatal mice with MIS gene or receptor mutation to determine if germ cell development was affected.

METHODS

Neonatal (5 MIS mutants, x1 MIS receptor mutant and 5 wild-type) and 10-day-old mice (x 7 MIS mutants, x1 MIS receptor mutant, 5 wild-type) were killed and prepared for hematoxylin-eosin and Masson trichrome histology of the testis. Testis diameter and tubule diameter were measured by Image-J, and germ cells were counted in 50 tubules/testis.

RESULTS

Total testis and tubular diameters were greater in wild-type vs MIS mutants at days 0 and 10 (P < .01). Gonocytes were decreased in MIS mutants vs wild-type on day 0 (P = .019), and on day 10, the number of type A spermatogonia was slightly decreased (P = .05) and type B spermatogonia were significantly decreased (P < .01). Similar results were seen in the MIS receptor knockout.

CONCLUSION

These results suggest that MIS has a previously unrecognized role in perinatal germ cell development that needs further investigation. Mullerian-inhibiting substance may be a possible future treatment for stimulating germ cell development in cryptorchidism.

摘要

目的

苗勒抑制物质(MIS)可能在出生后生殖细胞发育中起作用,尽管这尚未得到证实。阐明调节因子对于寻找预防隐睾症不育的新治疗方法至关重要。我们研究了具有 MIS 基因或受体突变的新生小鼠的生殖细胞发育,以确定生殖细胞发育是否受到影响。

方法

处死新生(5 个 MIS 突变体,1 个 MIS 受体突变体和 5 个野生型)和 10 天大的小鼠(7 个 MIS 突变体,1 个 MIS 受体突变体,5 个野生型),并准备对睾丸进行苏木精-伊红和 Masson 三色组织学检查。使用 Image-J 测量睾丸直径和小管直径,并在每个睾丸的 50 个小管中计数生殖细胞。

结果

与野生型相比,在第 0 天和第 10 天,MIS 突变体的总睾丸和小管直径更大(P <.01)。在第 0 天,MIS 突变体中的生殖细胞比野生型减少(P =.019),而在第 10 天,A型精原细胞的数量略有减少(P =.05),B 型精原细胞明显减少(P <.01)。在 MIS 受体敲除小鼠中也观察到了类似的结果。

结论

这些结果表明,MIS 在围产期生殖细胞发育中具有以前未被认识到的作用,需要进一步研究。苗勒抑制物质可能是一种未来治疗隐睾症刺激生殖细胞发育的潜在方法。

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1
Mullerian-inhibiting substance deficiency in transgenic mice interferes with postnatal germ cell development: clues for understanding infertility in cryptorchidism.转基因小鼠中 Mullerian 抑制物质缺乏会干扰生后生殖细胞发育:隐睾症不孕理解的线索。
J Pediatr Surg. 2009 Dec;44(12):2335-8. doi: 10.1016/j.jpedsurg.2009.07.058.
2
The müllerian inhibitor and mammalian sexual development.苗勒氏管抑制物与哺乳动物的性发育。
Philos Trans R Soc Lond B Biol Sci. 1995 Nov 29;350(1333):285-8; discussion 289. doi: 10.1098/rstb.1995.0163.
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Nature. 1990 May 10;345(6271):167-70. doi: 10.1038/345167a0.
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Autocrine and paracrine Müllerian inhibiting substance hormone signaling in reproduction.自分泌和旁分泌苗勒管抑制物质激素信号在生殖中的作用
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Genetic studies of MIS signalling in sexual development.性发育中苗勒管抑制物质信号传导的遗传学研究。
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Recombinant human Mullerian inhibiting substance inhibits long-term growth of MIS type II receptor-directed transgenic mouse ovarian cancers in vivo.重组人苗勒管抑制物质在体内抑制II型苗勒管抑制物质受体定向转基因小鼠卵巢癌的长期生长。
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Sites of transcription of the Müllerian inhibiting substance gene in mouse testis.小鼠睾丸中苗勒氏管抑制物质基因的转录位点。
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Mullerian inhibiting substance is required for germ cell proliferation during early gonadal differentiation in medaka (Oryzias latipes).在青鳉(Oryzias latipes)性腺早期分化过程中,缪勒氏抑制物质是生殖细胞增殖所必需的。
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