During human fetal development, sex differentiation occurs not only in the gonads but also in the adjacent developing reproductive tract. However, while the cellular composition of male and female human fetal gonads is well described, that of the adjacent developing reproductive tract remains poorly characterized. Here, we performed single-cell transcriptomics on male and female human fetal gonads together with the adjacent developing reproductive tract from first and second trimesters, highlighting the morphological and molecular changes during sex differentiation. We validated different cell populations of the developing reproductive tract and gonads and compared the molecular signatures between the first and second trimesters, as well as between sexes, to identify conserved and sex-specific features. Together, our study provides insights into human fetal sex-specific gonadogenesis and development of the reproductive tract beyond the gonads.

在人类胎儿发育过程中，性别分化不仅发生在性腺中，而且也发生在邻近发育中的生殖道中。然而，虽然男性和女性人类胎儿性腺的细胞组成已得到很好的描述，但邻近发育中的生殖道的细胞组成仍然知之甚少。在这里，我们对男性和女性人类胎儿性腺以及妊娠早期和中期的邻近发育生殖道进行了单细胞转录组学，突出了性别分化过程中的形态和分子变化。我们验证了发育中的生殖道和性腺的不同细胞群，并比较了妊娠早期和中期以及性别之间的分子特征，以确定保守的和性别特异性的特征。总之，我们的研究提供了对人类胎儿性别特异性性腺发生和性腺以外生殖道发育的​​见解。