We have tubes - lots of tubes. Compared to my house, my car, my bicycle - almost anything I can think of my body wins the tubing-complexity contest, hands down. The digestive system, the lymph system, the vascular system… each is remarkably complex, but efficient. The reproductive system is also heavy on very important plumbing - to get gametes in and out, for birthing young! Differences in reproductive-system plumbing between males and females are largely a consequence of early hormonal signaling. Both sexes begin with the same starting material, but either grow or degrade depending on the levels of specific hormones during development. A great deal of progress is being made to understand this embryonic endocrinology, which is particularly important in light of the potential endocrine-disrupting effects of the numerous xenobiotics in the environment. Both male and female reproductive systems first develop linear, cellular condensations in a head-to-tail direction within the mammalian embryo; these develop along both sides of the mid-line as an extension of the primitive kidney system. Eventually the tail-most segment of this developing tube degenerates in males and females, whereas the head-most part persist in males to form the efferent, or Wolffian (named after Caspar F. Wolff), ducts, within which sperm are transported out of the reproductive system. The Wolffian duct differentiates between Weeks 9 and 13 of gestation in the human male embryo (Embryonic Day 9 in mice), with the head-most region coiling to form the epididymis, while the tail-most region forms the vas deferens and, indirectly, the seminal vesicles. Thus, sperm developing in the gonad-derived seminiferous cords now have a way to get out into the world! That the Wolffian duct persists in the male is a result of the presence of testosterone in the developing male, and its absence in females. But plumbing wasn't Dr. Wolff's greatest accomplishments! He is most famous for his 1759 doctoral dissertation (Pay heed, graduate students of the world!) from the University of Halle, Theoria Generationis, in which he described embryonic development in both plants and animals as a process first involving the formation of distinct layers of cells. The conclusions of this remarkably analytical work from two kingdoms (!) seem obvious by today's standards, but at the time it was some of the best work in developmental biology. This model heavily influenced all subsequent theory and researchers of development, most notably Heinz Christian Pander and Karl Ernst von Baer, who used this foundation for building their own theories. According to von Baer, “[Wolff's thesis] is the greatest masterpiece of scientific observation which we possess.” Powerful words from an accomplished observer! The larger significance of this doctoral work is the foreshadowing of the concept of fundamental layers of an embryo, or germ layers, which Pander and von Baer explored more confidently than otherwise possible. It was not easy to come up with such a model that withstood the test of experimental time. The science was one thing, but these observations also contradicted contemporary dogma, which was the pet project of some very powerful (and close-minded) people. Wolff's work was strong support for the concept of epigenesis, the de novo development of structures within the embryo. This conclusion is diametrically opposed to the other prevailing theory of the time: preformation, or that the adult body is present within the egg, and development is an unfolding or expansion of the pre-existing structures. The preformation concept, aided by “observing/imagining” the homunculus, was a pet hypothesis (more a passion and belief) of Albrecht von Haller and his large group of followers. Given the bandwagon supporting the preformation model, it was quite difficult for Wolff to find employment after his thesis was published. Wolff was denied university professorships, so instead he began giving private, unsanctioned lectures on anatomy, physiology, and medicine in Berlin. In 1764, he published another paper, Theorie von der Generation, which responded to the criticisms of his dissertation and, in light of further consideration, emphasized his conclusions leading to epigenesist. Eventually, Wolff was offered a position in the anatomy department of the St. Petersburg Academy of Sciences, and moved to Russia in 1767, where he finished his career. There, Wolff continued to explore the anatomy of development, devoting a great deal of time to the study of embryos, and led to his discovery of the embryonic kidneys, or Wolffian bodies, whose tubes are also named in his honor. He is remembered today not just for his science, but for his strength to persevere and change the scientific world in fundamental ways through epigenesis, germ layers, and “plumbering”! Gary M. Wessel
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