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.

Testicular descent and cryptorchidism: the state of the art in 2004

“…At the cranial end of the urogenital ridge, the cranial suspensory ligament (CSL) regresses in male fetuses but not in female fetuses, which enables the gonadal position to be the vector sum of traction by the CSL vs the gubernaculum [12]. In female fetuses, the CSL holds the ovary high in the pelvis or abdominal cavity, depending on the species, whereas in male fetuses, the gubernaculum holds the testis near the inguinal canal [13].…”

Prenatal testosterone supplementation alters puberty onset, aggressive behavior, and partner preference in adult male rats

“…In a study performed by Henly et al [36], who used similar procedures to evaluate sexual behavior and sexual preference, no differences were found. An important difference between these experiments was the dose of TP and the period of treatment; in our study we used 1 mg/ animal/day on GD 17,18,and 19 whereas Henly et al [36] used 2 mg/0.1 ml/day on GD 16,17,18,19,and 20. Also in this study, males treated with TP from the day of birth through PND 21 and tested as intact adults spent more time with a sexually active male than with control males.…”

“…The dose used was on a per rat basis, without correction for body weight, in order to replicate methods used extensively by other investigators [5,19,20]. Additionally, a 1-mg dose was used because higher doses induce adverse effects including loss of litters, delayed delivery, decrease in pup weight, and extensive mortality in F1 females after weaning, because of reproductive tract malformations [5].…”

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.…”