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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review

Litter Size

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Disease relevance of Litter Size


Psychiatry related information on Litter Size

  • In PACAP(-/-) females, maternal crouching behavior tended to decrease compared to wild-type females, although the influence of litter size on maternal behavior needs to be considered [6].

High impact information on Litter Size

  • Analysis of wild-type and EP2-/- mice on day 5 of pregnancy indicated that the reduced litter size of EP2-/- mice is due to a pre-implantation defect [7].
  • Here we show that mice deficient for Gpr3 are unexpectedly fertile but display progressive reduction in litter size despite stable age-independent alteration of meiotic pause [8].
  • Nas1-/- females had a lowered fertility, with a 60% reduction in litter size [9].
  • Female mice lacking the gene encoding the prostaglandin (PG) E(2) receptor subtype EP(2) (EP(2)(-/-)) become pregnant and deliver their pups at term, but with a much reduced litter size [10].
  • The estrogen receptor locus is associated with a major gene influencing litter size in pigs [11].

Chemical compound and disease context of Litter Size


Biological context of Litter Size


Anatomical context of Litter Size


Associations of Litter Size with chemical compounds

  • Rats fed the metabolite sulphapyridine also had a reduced litter size when mated, while those fed the metabolite 5'aminosalicylic acid and a polymer of 5'aminosalicylic acid did not [12].
  • Female mice deficient in steroid 5alpha-reductase type 1 have a decreased litter size [26].
  • It has been found that maternal administration of hydroxyurea, mitomycin C, or 5-fluorouracil on day 9 of pregnancy, that is, when the fetal neural tube is in the final stages of closure, leads to a significant reduction in the proportion of NTD (to 15 to 20%) in the offspring, while total litter size is unaffected [27].
  • Ovarian venous progesterone concentration in lactating rats was elevated as litter size increased [28].
  • Lactose synthesis in the rat, and the effects of litter size and malnutrition [29].

Gene context of Litter Size

  • However, a small but significant reduction of the litter size by 23% was observed in Ceacam10(-/-) matings [30].
  • Here we report that ablation of the Bteb1 gene in female mice results in uterine hypoplasia, reduced litter size, and increased incidence of neonatal deaths in offspring [31].
  • Decreased Emx2 expression did not alter litter size [32].
  • In conclusion, these results indicate that the reduction of litter size in GHR/GHBP KO mice is the consequence of an alteration of the growth of follicles and suggest that the effects of GH effects on follicular growth are independent of IGF-I [33].
  • The Hexa-/- male mice were fertile; however, litter sizes were reduced [34].

Analytical, diagnostic and therapeutic context of Litter Size

  • CONCLUSION: Reduced uteroplacental perfusion pressure reduces litter size, fetal and placental weights, and maternal plasma leptin levels and increases placental expression of leptin receptors [35].
  • Animal model estimation of genetic parameters and response to selection for litter size and weight, growth, and backfat in closed seedstock populations of large white and Landrace swine [36].
  • The results on pregnancy length and litter size after progesterone injections in the experimental and respective control groups were as follows: 52.7 days and 4.3 kits, 51.3 days and 4.3 kits, 52.2 days and 5.8 kits, 50.2 days and 4.8 kits, 44.7 days and 5.6 kits, 46.0 days and 6.1 kits [37].
  • Some effects of litter size, ovariectomy and oestradiol (E2) on placental growth were determined [38].
  • Use of meta-analysis to combine candidate gene association studies: application to study the relationship between the ESR PvuII polymorphism and sow litter size [39].


  1. The uterine NK cell population requires IL-15 but these cells are not required for pregnancy nor the resolution of a Listeria monocytogenes infection. Barber, E.M., Pollard, J.W. J. Immunol. (2003) [Pubmed]
  2. The impact of maternal uterine genotype on postnatal growth and adult body size in mice. Cowley, D.E., Pomp, D., Atchley, W.R., Eisen, E.J., Hawkins-Brown, D. Genetics (1989) [Pubmed]
  3. Maternal protein restriction in the rat impairs resistance artery but not conduit artery function in pregnant offspring. Torrens, C., Brawley, L., Barker, A.C., Itoh, S., Poston, L., Hanson, M.A. J. Physiol. (Lond.) (2003) [Pubmed]
  4. A cholesterol-rich diet causes a greater hypercholesterolemic response in pregnant than in nonpregnant rats and does not modify fetal lipoprotein profile. Munilla, M.A., Herrera, E. J. Nutr. (1997) [Pubmed]
  5. Fetal and neonatal exposure to AZT and low-protein diet affects glucose homeostasis: a model with implications for AIDS prevention. Morten, K., Field, P., Ashley, N., Williams, K.A., Harris, D., Hartley, M., Clark, A., Poulton, J. Am. J. Physiol. Endocrinol. Metab. (2005) [Pubmed]
  6. Defects in reproductive functions in PACAP-deficient female mice. Shintani, N., Mori, W., Hashimoto, H., Imai, M., Tanaka, K., Tomimoto, S., Hirose, M., Kawaguchi, C., Baba, A. Regul. Pept. (2002) [Pubmed]
  7. Salt-sensitive hypertension and reduced fertility in mice lacking the prostaglandin EP2 receptor. Kennedy, C.R., Zhang, Y., Brandon, S., Guan, Y., Coffee, K., Funk, C.D., Magnuson, M.A., Oates, J.A., Breyer, M.D., Breyer, R.M. Nat. Med. (1999) [Pubmed]
  8. Premature ovarian aging in mice deficient for Gpr3. Ledent, C., Demeestere, I., Blum, D., Petermans, J., Hämäläinen, T., Smits, G., Vassart, G. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  9. Hyposulfatemia, growth retardation, reduced fertility, and seizures in mice lacking a functional NaSi-1 gene. Dawson, P.A., Beck, L., Markovich, D. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  10. Abortive expansion of the cumulus and impaired fertility in mice lacking the prostaglandin E receptor subtype EP(2). Hizaki, H., Segi, E., Sugimoto, Y., Hirose, M., Saji, T., Ushikubi, F., Matsuoka, T., Noda, Y., Tanaka, T., Yoshida, N., Narumiya, S., Ichikawa, A. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  11. The estrogen receptor locus is associated with a major gene influencing litter size in pigs. Rothschild, M., Jacobson, C., Vaske, D., Tuggle, C., Wang, L., Short, T., Eckardt, G., Sasaki, S., Vincent, A., McLaren, D., Southwood, O., van der Steen, H., Mileham, A., Plastow, G. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  12. Reversible male infertility due to sulphasalazine: studies in man and rat. O'Moráin, C., Smethurst, P., Doré, C.J., Levi, A.J. Gut (1984) [Pubmed]
  13. Combined effects of moderate ethanol consumption and a low-protein diet during gestation on brain development in BALB/c mice. Wainwright, P., Ward, G.R., Blom, K. Exp. Neurol. (1985) [Pubmed]
  14. Maternal and fetal brain and plasma levels of cocaine and benzoylecgonine after acute or chronic maternal intravenous administration of cocaine. Robinson, S.E., Enters, E.K., Jackson, G.F., Chinchilli, V.M., Maher, J.R., McDowell, K.P., Allen, H.M., Guo, H. J. Pharmacol. Exp. Ther. (1994) [Pubmed]
  15. Gestational and lactational exposure of rats to xenoestrogens results in reduced testicular size and sperm production. Sharpe, R.M., Fisher, J.S., Millar, M.M., Jobling, S., Sumpter, J.P. Environ. Health Perspect. (1995) [Pubmed]
  16. Lack of beneficial effects on the NO-donor, molsidomine, in the L-NAME-induced pre-eclamptic syndrome in pregnant rats. Richer, C., Boulanger, H., Es-Slami, S., Giudicelli, J.F. Br. J. Pharmacol. (1996) [Pubmed]
  17. A testicular germ cell-associated serine-threonine kinase, MAK, is dispensable for sperm formation. Shinkai, Y., Satoh, H., Takeda, N., Fukuda, M., Chiba, E., Kato, T., Kuramochi, T., Araki, Y. Mol. Cell. Biol. (2002) [Pubmed]
  18. Are BMP-15 and GDF-9 primary determinants of ovulation quota in mammals? Moore, R.K., Erickson, G.F., Shimasaki, S. Trends Endocrinol. Metab. (2004) [Pubmed]
  19. Alteration of maternal Hoxa10 expression by in vivo gene transfection affects implantation. Bagot, C.N., Troy, P.J., Taylor, H.S. Gene Ther. (2000) [Pubmed]
  20. Differential regulation of expression of genes encoding uncoupling proteins 2 and 3 in brown adipose tissue during lactation in mice. Pedraza, N., Solanes, G., Iglesias, R., Vázquez, M., Giralt, M., Villarroya, F. Biochem. J. (2001) [Pubmed]
  21. Impaired expression of the uncoupling protein-3 gene in skeletal muscle during lactation: fibrates and troglitazone reverse lactation-induced downregulation of the uncoupling protein-3 gene. Pedraza, N., Solanes, G., Carmona, M.C., Iglesias, R., Viñas, O., Mampel, T., Vazquez, M., Giralt, M., Villarroya, F. Diabetes (2000) [Pubmed]
  22. The early development of white adipose tissue. Effects of litter size on the lipoprotein lipase activity of four adipose-tissue depots, serum immunoreactive insulin and tissue cellularity during the first four weeks of life in the rat. Cryer, A., Jones, H.M. Biochem. J. (1979) [Pubmed]
  23. Alteration, by early underfeeding, of cellular multiplication and differentiation in the inguinal fat pads of rats. Gaben-Cogneville, A.M., Jahchan, T., Swierczewski, E. J. Nutr. (1981) [Pubmed]
  24. Effect of melatonin implants on reproduction in the male silver fox (Vulpes vulpes). Forsberg, M., Fougner, J.A., Hofmo, P.O., Einarsson, E.J. J. Reprod. Fertil. (1990) [Pubmed]
  25. Effects of litter size on protein, choline acetyltransferase (cat), and dopamine-beta-hydroxylase (DBH) of a mouse sympathetic ganglion. Gaetani, S., Mengheri, E., Spadoni, M.A., Rossi, A., Toschi, G. Brain Res. (1975) [Pubmed]
  26. Fetal death in mice lacking 5alpha-reductase type 1 caused by estrogen excess. Mahendroo, M.S., Cala, K.M., Landrum, D.P., Russell, D.W. Mol. Endocrinol. (1997) [Pubmed]
  27. The cause of neural tube defects: some experiments and a hypothesis. Seller, M.J. J. Med. Genet. (1983) [Pubmed]
  28. The role of LH in the luteotrophic process of lactating rats. Ford, J.J., Yoshinaga, K. Endocrinology (1975) [Pubmed]
  29. Lactose synthesis in the rat, and the effects of litter size and malnutrition. Wilde, C.J., Kuhn, N.J. Biochem. J. (1979) [Pubmed]
  30. Carcinoembryonic antigen-related cell adhesion molecule 10 expressed specifically early in pregnancy in the decidua is dispensable for normal murine development. Finkenzeller, D., Fischer, B., Lutz, S., Schrewe, H., Shimizu, T., Zimmermann, W. Mol. Cell. Biol. (2003) [Pubmed]
  31. Subfertility, uterine hypoplasia, and partial progesterone resistance in mice lacking the Kruppel-like factor 9/basic transcription element-binding protein-1 (Bteb1) gene. Simmen, R.C., Eason, R.R., McQuown, J.R., Linz, A.L., Kang, T.J., Chatman, L., Till, S.R., Fujii-Kuriyama, Y., Simmen, F.A., Oh, S.P. J. Biol. Chem. (2004) [Pubmed]
  32. Emx2 regulates mammalian reproduction by altering endometrial cell proliferation. Taylor, H.S., Fei, X. Mol. Endocrinol. (2005) [Pubmed]
  33. Growth hormone is required for ovarian follicular growth. Bachelot, A., Monget, P., Imbert-Bolloré, P., Coshigano, K., Kopchick, J.J., Kelly, P.A., Binart, N. Endocrinology (2002) [Pubmed]
  34. Characterization of the testis and epididymis in mouse models of human Tay Sachs and Sandhoff diseases and partial determination of accumulated gangliosides. Trasler, J., Saberi, F., Somani, I.H., Adamali, H.I., Huang, J.Q., Fortunato, S.R., Ritter, G., Gu, M., Aebersold, R., Gravel, R.A., Hermo, L. Endocrinology (1998) [Pubmed]
  35. Characterization of changes in leptin and leptin receptors in a rat model of preeclampsia. Anderson, C.M., Lopez, F., Zhang, H.Y., Pavlish, K., Benoit, J.N. Am. J. Obstet. Gynecol. (2005) [Pubmed]
  36. Animal model estimation of genetic parameters and response to selection for litter size and weight, growth, and backfat in closed seedstock populations of large white and Landrace swine. Ferraz, J.B., Johnson, R.K. J. Anim. Sci. (1993) [Pubmed]
  37. Effect of progesterone and medroxyprogesterone acetate on pregnancy length and litter size in mink. Jarosz, S.J., Dukelow, W.R. Lab. Anim. Sci. (1985) [Pubmed]
  38. Do oestrogens regulate placental growth in the mouse? Miller, B.G. Aust. J. Biol. Sci. (1980) [Pubmed]
  39. Use of meta-analysis to combine candidate gene association studies: application to study the relationship between the ESR PvuII polymorphism and sow litter size. Alfonso, L. Genet. Sel. Evol. (2005) [Pubmed]
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