Anti-müllerian hormone in relation to the growth and differentiation of the gubernacular primordia in mice.

The present study analysed gubernaculum development in mice that had been induced, through transgenesis, to express human anti-Müllerian hormone (h-AMH) throughout prenatal life. Growth and differentiation of the gubernacular primordia were assessed through the analysis of serial, transverse or sagittal, histological sections of the lower abdomen. Transgenic males and females expressed biologically active amounts of h-AMH as measured by sensitive and specific ELISA and evidenced through the regression, in females, of Müllerian ducts after day 13 of prenatal life. Gubernacular primordia became distinguishable at the same age in control and transgenic male and female fetuses on day 12 after coitus. In both groups gubernacular cords (inguinal folds of the genital mesenteries) increased in length more in females than in males while gubernacular cones showed larger growth in males. h-AMH thus appeared not to affect the sexually dimorphic pattern of growth and development of these structures. Growth and differentiation of the gubernacular primordia was further examined in 18-day-old control and h-AMH transgenic fetuses that had been exposed to testosterone propionate injected into their mothers on days 12 and 14 of pregnancy. Testosterone treatment affected, to a minor extent, the growth of the female gubernacular cords: these were reduced in length (but had a larger surface area) compared with controls. The gubernacular cones were slightly increased in length but male-like differentiation of the tissues of the cones into a muscular and mesenchymal component was not noticed to any extent. The observations thus add experimental support to the contention that AMH, even in combination with testosterone, is not effective in establishing the male pattern of gubernacular primordia development.

Ontogeny of reproductive abnormalities induced by deregulation of anti-müllerian hormone expression in transgenic mice.

Anti-müllerian hormone, normally responsible for the regression of müllerian ducts in male fetuses, induces stunting, germ cell loss, and seminiferous tubule formation in ovaries of bovine freemartin fetuses and of transgenic mice, which express the human anti müllerian hormone gene under the control of the metallothionein promoter. Because the latter have been studied only after birth, we undertook a detailed chronological study of their reproductive organs. Müllerian ducts of transgenic female fetuses regressed at the same time as those of normal or transgenic males. Maximal reduction of germ cell number occurred between 16 days postcoitus and birth, when most transgenic oocytes were still in the leptotene stage of the meiotic prophase, whereas normal oocytes had already reached the pachytene phase. Interference with progression of the meiotic prophase and germ cell loss in the fetal ovary are probably responsible for subsequent ovarian regression and retardation of follicle growth. Seminiferous tubule formation was not detectable prior to birth and occurred only rarely in postnatal ovaries. Aromatase activity of fetal transgenic ovaries was decreased, as well as serum concentration of testosterone in adult transgenic males, suggesting that high levels of anti-müllerian hormone may impair Leydig cell steroidogenesis.