Effect of androgens on the cranial suspensory ligament and ovarian position

Abstract

Androgens have been postulated to have a major role in testicular descent via regression of the cranial suspensory ligament, which in normal rodents anchors the ovary to the retroperitoneum near the lower pole of the kidney. This study aimed to quantitate the degree of descent of the foetal ovary in androgen-treated female mice to determine the role of androgens in regression of the cranial suspensory ligament and descent of the testis. Time-pregnant mice were injected with testosterone propionate or methyl testosterone (2.5-3.0 mg) in vehicle on day 13 or 14. Control animals received vehicle only. Newborn mice were anaesthetised and dissected for macroscopic anatomy of the ovary, which was quantified by measuring the vertical distance from the lower pole of the kidney to the lower pole of the ovary. Histological analysis was also performed. The external genitalia were masculinised in all females exposed to prenatal androgens. The ovaries of treated animals were mobile, with no cranial suspensory ligament, and located slightly caudal to the kidney. Wolffian duct structures were identifiable, but the gubernaculum was qualitatively unchanged compared with control females. The ovary was displaced caudally (P< 0.001), but only 15-25% of the distance to the lower abdomen. Exogenous androgens induce regression of the cranial suspensory ligament, causing the ovary to be more mobile and lower in the abdominal cavity. However, since the testicular position at birth is at or below the bladder neck, androgen-mediated regression of the cranial suspensory ligament is only an adjunct to the control of transabdominal testicular descent.

Effects of Prenatal Testosterone Propionate on the Sexual Development of Male and Female Rats: A Dose-Response Study

“…Elongation of ovarian ligament, as measured by kidney-toovary distance, occurred only in the high dose groups. This measurement was increased in a previous study in which females were exposed in utero to androgens (Lee and Hutson, 1999) and indicates masculinization, although only with high levels of androgen.…”

“…All chemicals were obtained from Sigma (St. Louis, MO) unless otherwise noted. Doses used were on a per rat basis without correction for body weight in order to replicate methods used extensively by other investigators (Greene et al, 1939;Kawashima et al, 1978;Lee and Hutson, 1999;McCoy and Shirley, 1992;Rhees et al, 1997;Swanson and van der Werff ten Bosch, 1965).…”

Epidemiology and pathogenesis of cryptorchidism

“…In addition to the development of the gubernaculum, the regression of the cranial suspensory ligament of the gonad also seems to contribute to the positioning of the gonad, at least in mice (Lee and Hutson, 1999). This regression is dependent on androgens and accordingly, female mice exposed prenatal to androgens show minor descent of the ovaries (Lee and Hutson, 1999) and male mice mutant for androgen receptor gene show retention of the cranial suspensory ligament (Zimmermann et al, 1999).…”

Effect of an anti-androgen on testicular descent and inguinal closure in a marsupial, the tammar wallaby (Macropus eugenii)

“…In humans and animals with androgen resistance (Wensing, 1973;Wensing et al, 1975;Fentener van Vlissingen et al, 1988;Barthold et al, 2000) or after treatment with the androgen receptor inhibitor flutamide (Shono et al, 1994;Cain et al, 1995), the gubernaculum swells and transabdominal migration occurs. However, androgens are required for regression of the cranial suspensory ligament, as the ligament fails to regress in testicular feminized (tfm) males or male rodent fetuses exposed to anti-androgens (van der Schoot and Elger, 1992; Lee and Hutson, 1999). Testosterone treatment of female rodent fetuses induces the regression of the cranial suspensory ligament allowing the ovaries to move to a lower position in the abdomen (van der Schoot, 1993;Emmen et al, 1998;Lee and Hutson, 1999).…”

“…However, androgens are required for regression of the cranial suspensory ligament, as the ligament fails to regress in testicular feminized (tfm) males or male rodent fetuses exposed to anti-androgens (van der Schoot and Elger, 1992; Lee and Hutson, 1999). Testosterone treatment of female rodent fetuses induces the regression of the cranial suspensory ligament allowing the ovaries to move to a lower position in the abdomen (van der Schoot, 1993;Emmen et al, 1998;Lee and Hutson, 1999). Androgens also affect inguinoscrotal descent.…”