Department of Physiological Sciences, University of Florida, Gainesville, FL 32610, USA.
Mol Hum Reprod. 2013 Sep;19(9):547-58. doi: 10.1093/molehr/gat031. Epub 2013 Apr 25.
Development of uterine glands (adenogenesis) in mammals typically begins during the early post-natal period and involves budding of nascent glands from the luminal epithelium and extensive cell proliferation in these structures as they grow into the surrounding stroma, elongate and mature. Uterine glands are essential for pregnancy, as demonstrated by the infertility that results from inhibiting the development of these glands through gene mutation or epigenetic strategies. Several genes, including forkhead box A2, beta-catenin and members of the Wnt and Hox gene families, are implicated in uterine gland development. Progestins inhibit uterine epithelial proliferation, and this has been employed as a strategy to develop a model in which progestin treatment of ewes for 8 weeks from birth produces infertile adults lacking uterine glands. More recently, mouse models have been developed in which neonatal progestin treatment was used to permanently inhibit adenogenesis and adult fertility. These studies revealed a narrow and well-defined window in which progestin treatments induced permanent infertility by impairing neonatal gland development and establishing endometrial changes that result in implantation defects. These model systems are being utilized to better understand the molecular mechanisms underlying uterine adenogenesis and endometrial function. The ability of neonatal progestin treatment in sheep and mice to produce infertility suggests that an approach of this kind may provide a contraceptive strategy with application in other species. Recent studies have defined the temporal patterns of adenogenesis in uteri of neonatal and juvenile dogs and work is underway to determine whether neonatal progestin or other steroid hormone treatments might be a viable contraceptive approach in this species.
哺乳动物的子宫腺（腺发生）发育通常始于出生后的早期阶段，涉及从腔上皮出芽形成新生腺体，以及这些结构在生长为周围基质、伸长和成熟过程中的广泛细胞增殖。子宫腺对于妊娠至关重要，这可以通过基因突变或表观遗传策略抑制这些腺体的发育导致的不孕来证明。几种基因，包括叉头框 A2、β-连环蛋白以及 Wnt 和 Hox 基因家族的成员，都与子宫腺发育有关。孕激素抑制子宫上皮细胞增殖，这已被用作一种策略，即用孕激素处理出生后的母羊 8 周，产生缺乏子宫腺的不孕成年母羊。最近，开发了一些小鼠模型，其中使用新生期孕激素处理来永久抑制腺发生和成年生育能力。这些研究揭示了一个狭窄而明确的窗口期，在此期间，孕激素处理通过损害新生儿腺发育并建立导致植入缺陷的子宫内膜变化，导致永久性不孕。这些模型系统正被用于更好地理解子宫腺发生和子宫内膜功能的分子机制。新生期孕激素处理在绵羊和小鼠中产生不孕的能力表明，这种方法可能为其他物种提供一种可行的避孕策略。最近的研究已经确定了新生和幼年犬子宫腺发生的时间模式，正在努力确定新生期孕激素或其他类固醇激素处理是否可能成为该物种的可行避孕方法。
