Development of fetal testicular cells in androgen receptor deficient mice

Area of Science:

• Reproductive biology
• Endocrinology
• Developmental biology

Background:

• Androgens are crucial for male reproductive tract masculinization during mammalian development.
• The male germ line shows heightened sensitivity to anti-androgenic endocrine disruptors during the embryonic period.
• Previous research indicated androgens control fetal male germ cell growth.

Purpose of the Study:

• To investigate the presence and function of androgen receptors in fetal male germ cells (gonocytes) during later fetal development.
• To examine the impact of androgens on somatic testicular cell development using Tfm mice with a non-functional androgen receptor.
• To elucidate novel mechanisms of androgen action on gonocytes.

Main Methods:

• Utilized Tfm mice, which possess a mutation inactivating the androgen receptor.
• Examined the presence of functional androgen receptors in fetal gonocytes.
• Assessed the effects of androgens on fetal Leydig and Sertoli cell development.

Main Results:

• A functional androgen receptor was identified in fetal gonocytes during the latter part of fetal life.
• Fetal Leydig cells demonstrated relative independence from endogenous androgens.
• Fetal Sertoli cell numbers decreased, linked to impaired peritubular myoid cell differentiation, in the absence of functional androgen receptors.

Conclusions:

• Gonocytes are identified as a specific target for androgens during the embryonic period.
• A novel mechanism of androgen action on gonocytes has been indicated.
• Understanding this pathway is vital for clarifying fetal testis physiology and the impact of environmental anti-androgens.