Novel function of LHFPL2 in female and male distal reproductive tract development

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Genitalia / growth & development*
  • Genitalia / metabolism*
  • Hearing Loss, Sensorineural / genetics
  • Hearing Loss, Sensorineural / metabolism*
  • Infertility, Female / genetics*
  • Infertility, Female / pathology
  • Male
  • Mice
  • Mullerian Ducts / growth & development
  • Mullerian Ducts / metabolism
  • Ovary / growth & development
  • Ovary / metabolism
  • Point Mutation
  • Reproduction / genetics*
  • Sex Differentiation / genetics
  • Urogenital System / growth & development
  • Urogenital System / metabolism
  • Urogenital System / pathology
  • Wolffian Ducts / growth & development
  • Wolffian Ducts / metabolism

Supplementary concepts

  • Deafness, Autosomal Recessive 67