Zhao Fei, Zhou Jun, Li Rong, Dudley Elizabeth A, Ye Xiaoqin
Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
Interdisciplinary Toxicology Program, University of Georgia, Athens, GA 30602, USA.
Sci Rep. 2016 Mar 11;6:23037. doi: 10.1038/srep23037.
Congenital reproductive tract anomalies could impair fertility. Female and male reproductive tracts are developed from Müllerian ducts and Wolffian ducts, respectively, involving initiation, elongation and differentiation. Genetic basis solely for distal reproductive tract development is largely unknown. Lhfpl2 (lipoma HMGIC fusion partner-like 2) encodes a tetra-transmembrane protein with unknown functions. It is expressed in follicle cells of ovary and epithelial cells of reproductive tracts. A spontaneous point mutation of Lhfpl2 (LHFPL2(G102E)) leads to infertility in 100% female mice, which have normal ovarian development, ovulation, uterine development, and uterine response to exogenous estrogen stimulation, but abnormal upper longitudinal vaginal septum and lower vaginal agenesis. Infertility is also observed in ~70% mutant males, which have normal mating behavior and sperm counts, but abnormal distal vas deferens convolution resulting in complete and incomplete blockage of reproductive tract in infertile and fertile males, respectively. On embryonic day 15.5, mutant Müllerian ducts and Wolffian ducts have elongated but their duct tips are enlarged and fail to merge with the urogenital sinus. These findings provide a novel function of LHFPL2 and a novel genetic basis for distal reproductive tract development; they also emphasize the importance of an additional merging phase for proper reproductive tract development.
先天性生殖道异常可能会损害生育能力。女性和男性生殖道分别由苗勒管和沃尔夫管发育而来，涉及起始、延长和分化过程。目前对于远端生殖道发育的遗传基础知之甚少。Lhfpl2（脂肪瘤HMGIC融合伴侣样2）编码一种功能未知的四跨膜蛋白。它在卵巢的卵泡细胞和生殖道的上皮细胞中表达。Lhfpl2的一个自发点突变（LHFPL2(G102E)）导致100%的雌性小鼠不育，这些雌性小鼠卵巢发育、排卵、子宫发育以及子宫对外源性雌激素刺激的反应均正常，但存在上纵行阴道纵隔和下阴道闭锁异常。在约70%的突变雄性小鼠中也观察到不育，这些雄性小鼠交配行为和精子数量正常，但远端输精管盘曲异常，分别导致不育和可育雄性小鼠的生殖道完全和不完全阻塞。在胚胎第15.5天，突变的苗勒管和沃尔夫管已经延长，但其管尖增大，无法与泌尿生殖窦融合。这些发现揭示了LHFPL2的新功能以及远端生殖道发育的新遗传基础；它们还强调了额外的融合阶段对于正常生殖道发育的重要性。
