Receptivity of the human male and female fetal caudal genital ligament to gonadal hormones.

Abstract

In briefCurrent understanding of testicular descent mechanisms, mainly based on rodent models, attributes a central role to testicular hormones. This study examines the hormonal receptivity and potential sex differences of human caudal genital ligaments (also named gubernaculum in males) during organogenesis. Abstract In both sexes, fetal gonads are connected to the abdominal wall by caudal genital ligaments (CGLs). The male CGL (gubernaculum testis) drives testis descent under the influence of testicular hormones, whereas the fate of the female CGL is thought to result from the absence of these hormones. However, the process in humans has not been clearly demonstrated. We here examined the expression patterns of receptors and metabolizing enzymes of gonadal hormones in CGLs collected from male and female human first trimester fetuses and from boys with uni- or bi-lateral cryptorchidism by using real-time quantitative PCR, in situ hybridisation, and when possible, immunostaining. We show that the CGLs of both sexes express receptors for insulin-like factor 3 (RXFP2), androgens, estrogens, and for members of the transforming growth factor beta family during the first trimester of pregnancy. The expression of RXFP2 increased with fetal age in both sexes, was heterogeneous, and was unrelated to proliferation. Androgen receptor expression also tended to increase with age, particularly in males. Notably, five alpha reductase type 2 (SRD5A2) and estrogen receptor (ESR1) mRNA levels increased significantly with age in both sexes, but showed clear sexual dimorphism. In contrast, ACVR2B and BMPR1B mRNA decreased with age in both sexes, unlike stable levels of AMHR2 mRNA. In boys with cryptorchidism, gene expression remained consistent regardless of age, ligament position, or appearance. The expression of male hormone receptors and the increased expression of ESR1 in female CGLs raises questions about their physiological significance and susceptibility to xenoestrogens during early development.