Role of the fetal pituitary in cryptorchidism induced by exogenous maternal oestrogen during pregnancy in mice

Abstract

A single subcutaneous injection of 5 or 1 mg oestradiol given to pregnant female mice on Day 14 of pregnancy resulted in all male offspring being cryptorchid. Pituitary LH content, testicular weights and structure, seminal vesicle weights and the structure of the reproductive tract as a whole were monitored on the day of birth and at 2, 4, 8 and 14 weeks of age. Apart from an initial significant reduction in pituitary LH at the time of birth, no other marked differences were seen between control and treated animals except that all oestrogen-treated males lacked a gubernaculum and the testes were freely mobile within the abdomen. Hypogonadal (hpg) male mice lacking GnRH are cryptorchid but have a normal gubernaculum and their testes develop and descend normally if treated with gonadotrophins. When the mothers of hpg mice were treated with oestradiol the male offspring lacked a gubernaculum. These results indicate that perturbations of the fetal hypothalamic/pituitary axis play no significant part in oestrogen-induced cryptorchidism in mice.

Maternal hormone levels in early gestation of cryptorchid males: a case-control study

“…Hadziselimovic & Herzog (1980) proposed that the mechanism responsible for this effect is the suppression of foetal androgen secretion by oestrogen. It has, however, recently been shown in studies of hypogonadal mice that foetal testosterone production in early gestation is not relevant to the aetiology of cryptorchidism (Charlton, 1986;Grocock et al, 1988). Current thinking (Hutson & Donahoe, 1986) considers a biphasic model for the hormonal control of testicular descent.…”

“…The first stage is thought to be regulated by mullerian inhibiting substance, whereas the second, later stage is androgen dependent. Based on animal data, it appears that estrogens inhibit mullerian inhibiting substance (Newbold et al, 1984;Hutson et al, 1985) and cause atrophy of the gubernaculum (Wensing, 1973;Grocock et al, 1988).…”

Testicular Descent

“…9,43,86 Gubernacular migration beyond the inguinal region is absent in gonadotropin-deficient animals 137 as well as in both Tfm animals and humans with complete androgen resistance. 57 Furthermore, about 50% of animals treated prenatally with flutamide exhibit deraranged gubernacular migration and delayed regression.…”

Hormones in male sexual development

“…In rodents, the classical experimental model for intraabdominal cryptorchidism is produced by exposing pregnant female to exogenous estrogens (Greene et al 1942;Grocock et al 1988). The effects of estradiol include reduction of gubernacular outgrowth, induction of estrogen receptors within Wolffian ducts, and stabilization of Mü llerian ducts.…”