Modification of embryonic development of reproductive and lymphoid organs in the chick.

Following the publication of Lillie's (1917) observations and theories on the endocrine basis of the development of the bovine freemartin, experiments were initiated to determine if heterosexual gonad grafts to the chorio-alantoic membrane of chicks could stimulate formation of intersexes (Willier, 1927). Hormone extracts of testes and urine were used by Dantchakoff (1935) and Kozelka & Gallagher (1934), and synthetic hormones were tested in the chick by Wolff & Ginglinger (1935). Estrogens feminized the left gonad of male embryos and resulted in retention of Mullerian ducts in males and occasional cystic development of Mullerian ducts in females. Less extensive feminization of the left testis, dilation of Wolffian ducts, and partial deletion of Mullerian ducts occurred in androsterone-treated embryos (Wolff, 1935). Sensitivity of the genital papilla to exogenous steroids was described by Reinbold (1951). Riddle & Dunham (1942) demonstrated that a single injection of estradiol benzoate into laying birds resulted in feminization of genetic males which developed from ova released shortly thereafter. Lutz & Lutz-Ostertag (1959) described spontaneous chick freemartins developing in double-yolked eggs. Studies of individual male embryos which had access to the resources of two yolks in double-yolked eggs (Ruch, 1961) revealed the occurrence of gonadal modifications similar to those resulting from administration of estrogens or from implantation of female gonads adjacent to the genital ridge of young male embryos (Wolff, 1946-47). When heterosexual implants of gonads of sufficient size were placed on the chorioallantoic membrane, male left testes developed into ovotestes and Mullerian ducts were reduced in the female (GroenedijkHuijbers, 1960). The immunological consequences of vascular anastomoses between bovine twins discussed by Owen (1945), and more recently by Fecheimer, Herschler & Gilmore (1963) and Goodfellow, Strong & Stewart (1965) afford an additional point of departure in studying the freemartin. For several years we have been studying the effects of steroid compounds on the development of the reproductive system of the chick embryo (Pincus & Hopkins, 1958; Pincus & Erickson, 1962). The sensitivity of the testis and Mullerian duct of the avian embryo to estrogens, the contrast of 'feminization'