Genetic Influences on the Timing of Puberty in Mice1

Nelson, James F.; Karelus, Katarzyna; Felicio, Lêda S.; Johnson, Thomas E.

doi:10.1095/biolreprod42.4.649

Cited by 165Hypothalamic control of reproductive hormonesReproductive Biology and FertilitySexual Differentiation and Disorders

Genetic Influences on the Timing of Puberty in Mice1

Nelson, James F., Karelus, Katarzyna, Felicio, Lêda S., Johnson, Thomas E.·1990·Biology of Reproduction

DOI 10.1095/biolreprod42.4.649

Open this paper in CoChat — free account

Abstract

Genetic influences on the timing of three pubertal events--vaginal opening, first vaginal cornification, and onset of cyclicity--were studied in C57BL/6J, DBA/2J, and C3H/HeJ mice and in two F1 hybrid strains (B6D2F1 and B6C3HF1). Marked genotypic differences were found. Among inbred strains, differences in the onset of vaginal opening and first vaginal cornification (C3H less than DBA less than C57) did not parallel those for the onset of cyclicity (C3H much greater than DBA = C57). Compared to parental strains, F1 hybrid strains were intermediate for times of vaginal opening and first vaginal cornification, consistent with the model in which the genetic effects on the timing of these events are additive. By contrast, onset of cyclicity occurred significantly earlier in the F1 hybrids than in their parent strains, indicating heterosis for one or more genes specifying this event. Body weights also differed among the genotypes from weaning onward, but these differences were only partially correlated with the differences in the timing of the pubertal events. Thus, genetic influences other than those affecting body weight contribute to the differential timing of pubertal events in these mouse strains. These results reveal marked genetic variation in the timing of puberty, and indicate that the set of genes specifying the timing of vaginal opening and first vaginal cornification differs from those specifying the onset of cyclicity.

Integrity signals

Registry

Crossref · 10.1095/biolreprod42.4.649

Cites

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

In female rodents, vaginal opening is followed some days later by first estrus and a few days later by onset of regular cyclicity.
“This is followed some days later by first estrus and a few days later by onset of regular cyclicity”
From Does puberty mark a transition in sensitive periods for plasticity in the associative neocortex? (2017) · cites this paper as Nelson et al., 1990

Sorted by citations

Leptin accelerates the onset of puberty in normal female mice.
Ahima, R. S., Dushay, J. R., Flier, S. N., Prabakaran, D., & Flier, J. S. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119172 · Cited by 755 · see citing works
Early Marriage, Age of Menarche, and Female Schooling Attainment in Bangladesh
Field, E., & Ambrus, A. (2008) · Journal of Political Economy · doi:10.1086/593333 · Cited by 592 · see citing works
“1991) and animal studies (Nelson et al. 1990).”
Adolescent changes in the homeostatic and circadian regulation of sleep
Hagenauer, M. H., Perryman, J. I., Lee, T. M., & Carskadon, M. A. (2009) · Developmental Neuroscience · doi:10.1159/000216538 · Cited by 593 · see citing works
Leptin’s effect on puberty in mice is relayed by the ventral premammillary nucleus and does not require signaling in Kiss1 neurons
Donato, J., Cravo, R. M., Frazão, R., Gautron, L., Scott, M. M., Lachey, J. L., de Castro, I. A., Margatho, L. O., Lee, S., Lee, C., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci45106 · Cited by 356 · see citing works
Establishing a Framework for the Functional Mammary Gland: From Endocrinology to Morphology
Hovey, R. C., Trott, J. F., & Vonderhaar, B. K. (2002) · Journal of Mammary Gland Biology and Neoplasia · doi:10.1023/a:1015766322258 · Cited by 303 · see citing works
“Complete cyclicity then commences approximately 2 weeks after the first detection of vaginal cornification, although the timing of this onset is strain-dependent (60).”
Background
Lifetime development of behavioural phenotype in the house mouse (Mus musculus)
Brust, V., Schindler, P. M., & Lewejohann, L. (2015) · Frontiers in Zoology · doi:10.1186/1742-9994-12-s1-s17 · Cited by 269 · see citing works
“[16-19]).”
Does puberty mark a transition in sensitive periods for plasticity in the associative neocortex?
Piekarski, D. J., Johnson, C. M., Boivin, J. R., Thomas, A. W., Lin, W. C., Delevich, K., M. Galarce, E., & Wilbrecht, L. (2017) · Brain Research · doi:10.1016/j.brainres.2016.08.042 · Cited by 175 · see citing works
“This is followed some days later by first estrus and a few days later by onset of regular cyclicity (Nelson et al., 1990).”
Background
Normal Female Sexual Development Requires Neuregulin–erbB Receptor Signaling in Hypothalamic Astrocytes
Prévot, V., Río, C., Cho, G. J., et al. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-01-00230.2003 · Cited by 177 · see citing works
“Ovulation normally occurs on the day of estrus, but in mice it cannot be assumed to occur unless vaginal cornification is followed by the appearance of a predominance of leukocytes in the vaginal lavage (Nelson et al., 1990).”
Background
The neuroendocrine control of the circadian system: Adolescent chronotype
Hagenauer, M. H., & Lee, T. M. (2012) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2012.04.003 · Cited by 143 · see citing works
Long-Term Behavioral Effects of Post-weaning Social Isolation in Males and Females
Walker, D. M., Cunningham, A. M., Gregory, J. K., & Nestler, E. J. (2019) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2019.00066 · Cited by 139 · see citing works
Distinct Physiological Maturation of Parvalbumin-Positive Neuron Subtypes in Mouse Prefrontal Cortex
Miyamae, T., Chen, K., Lewis, D. A., & González‐Burgos, G. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.3325-16.2017 · Cited by 124 · see citing works
“To assess PV neuron development, including the onset of puberty at P21 (Nelson et al., 1990; Laviola et al., 2003) and into adolescence, we studied G42 mice between P8 and P70.”
BackgroundMethodInfluential
Effects of early prepubertal exposure to bisphenol A on the onset of puberty, ovarian weights, and estrous cycle in female mice
Nah, W. H., Park, M. J., & Gye, M. C. (2011) · Daehan saengsik uihak hoeji/Clinical and experimental reproductive medicine · doi:10.5653/cerm.2011.38.2.75 · Cited by 125 · see citing works
“Though the onset of puberty is a genetically driven event [8], it can be changed by environmental factors [9], nutritional states, and metabolic status.”
Background
Enhanced at puberty 1 (EAP1) is a new transcriptional regulator of the female neuroendocrine reproductive axis
Heger, S., Mastronardi, C. A., Dissen, G. A., Lomniczi, A., Cabrera, R., Roth, C. L., Jung, H., Galimi, F., Sippell, W. G., & Ojeda, S. R. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31752 · Cited by 118 · see citing works
Alteration in Neonatal Nutrition Causes Perturbations in Hypothalamic Neural Circuits Controlling Reproductive Function
Caron, É., Ciofi, P., Prévot, V., & Bouret, S. G. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.6074-11.2012 · Cited by 112 · see citing works
“Thereafter, vaginal smears were examined daily to detect the first ovulation (used as a marker of puberty onset), as described previously (Nelson et al., 1990; Prevot et al., 2005).”
Method
Prenatal Perfluorooctanoic Acid Exposure in CD-1 Mice: Low-Dose Developmental Effects and Internal Dosimetry
Macon, M. B., Villanueva, L. R., Tatum-Gibbs, K. R., ZEHR, R. D. J., Strynar, M. J., Stanko, J. P., White, S. S., Helfant, L., & Fenton, S. E. (2011) · Toxicological Sciences · doi:10.1093/toxsci/kfr076 · Cited by 110 · see citing works
“We postulate that intraspecies differences in effects are more likely due to the timing of exposure, as there are strain differences in timing of puberty (Nelson et al., 1990); yet, mammary gland morphology remains fairly consistent during stages of development (i.”
Background
The mammary gland is a sensitive pubertal target in CD-1 and C57Bl/6 mice following perinatal perfluorooctanoic acid (PFOA) exposure
Tucker, D. K., Macon, M. B., Strynar, M. J., Dagnino, S., Andersen, E., & Fenton, S. E. (2015) · Reproductive Toxicology · doi:10.1016/j.reprotox.2014.12.002 · Cited by 101 · see citing works
“Visual assessment for VO started on PND 18 in CD-1 mice and on PND 23 in C57Bl/6 mice, as VO has been reported to begin as late as PND 30 in that strain [30].”
Method
Sexually dimorphic neuronal responses to social isolation
Senst, L., Baimoukhametova, D., Sterley, T.-L., & Bains, J. S. (2016) · eLife · doi:10.7554/elife.18726 · Cited by 101 · see citing works
“The age of pre-adolescent mice (post-natal day 21–35) was determined according to previous literature demonstrating that in C57/BL mice the onset of puberty occurs at approximately 5 weeks of age (Nelson et al., 1990; Mayer et al., 2010).”
BackgroundMethod
Correlations among Three Measures of Puberty in Mice and Relationships with Estradiol Concentration and Ovulation1
Safranski, T. J., Lamberso, W. R., & Keisler, D. H. (1993) · Biology of Reproduction · doi:10.1095/biolreprod48.3.669 · Cited by 85 · see citing works
erbB-1 and erbB-4 Receptors Act in Concert to Facilitate Female Sexual Development and Mature Reproductive Function
Prévot, V., Lomniczi, A., Corfas, G., et al. (2005) · Endocrinology · doi:10.1210/en.2004-1146 · Cited by 81 · see citing works
“Although ovulation normally occurs on the day of estrous (14), detection of cornified cells in mice cannot be assumed to indicate that ovulation has occurred, unless vaginal cornification is followed by the appearance of a predominance of leukocytes (15).”
Background
Intestinal immune responses in wild-type and Apcmin/+ mouse, a model for colon cancer.
Kettunen, H., Kettunen, A., & Rautonen, N. (2003) · PubMed · Cited by 75 · see citing works
Deletion of theTtf1Gene in Differentiated Neurons Disrupts Female Reproduction without Impairing Basal Ganglia Function
Mastronardi, C. A., Smiley, G. G., Raber, J., Kusakabe, T., Kawaguchi, A., Matagne, V., Dietzel, A., Heger, S., Mungenast, A. E., Cabrera, R., et al. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.4238-06.2006 · Cited by 69 · see citing works
“Ovulation normally occurs on the day of estrus, but in mice it is not certain (Stiff et al., 1974; Nelson et al., 1990) unless vaginal cornification is followed by the appearance of a predominance of leukocytes in the vaginal lavage (Prevot et al., 2003a).”
Background
Puberty in Mice and Rats
Prévot, V. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-397175-3.00030-2 · Cited by 78 · see citing works
Hyperandrogenemia Induced by Letrozole Treatment of Pubertal Female Mice Results in Hyperinsulinemia Prior to Weight Gain and Insulin Resistance
Skarra, D. V., Hernandez, A. M., Rivera, A. J., Anvar, A. R., & Thackray, V. G. (2017) · Endocrinology · doi:10.1210/en.2016-1898 · Cited by 68 · see citing works
“cyclicity is established by 8 weeks of age (55).”
Background
Mechanisms for the Regulation of Gonadotropin-Releasing Hormone Gene Expression in the Developing Mouse1
Gore, A. C., Roberts, J. L., & Gibson, M. J. (1999) · Endocrinology · doi:10.1210/endo.140.5.6711 · Cited by 68 · see citing works
Reproductive dysfunction and decreased GnRH neurogenesis in a mouse model of CHARGE syndrome
Layman, W. S., Hurd, E. A., & Martin, D. M. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr216 · Cited by 68 · see citing works
“For example, vaginal opening in wild-type female mice is dependent upon attainment of a threshold body size (40).”
BackgroundInfluential
Scent marking behavior in male C57BL/6J mice: Sexual and developmental determination
Arakawa, H., ARAKAWA, K., Blanchard, D. C., & Blanchard, R. J. (2007) · Behavioural Brain Research · doi:10.1016/j.bbr.2007.05.007 · Cited by 65 · see citing works
“Thus, even though 60 days is well above the period when copulation begins in male mice [45], this suggests that scent marking of an unknown area containing a female may be a particularly dangerous undertaking for a young and small, albeit sexually mature, male.”
Background
Overexpression of a human transforming growth factor-alpha (TGF alpha) transgene reveals a dual antagonistic role of TGF alpha in female sexual development
Ma, Y. J., Dissen, G. A., Merlino, G. T., Coquelin, A., & Ojeda, S. R. (1994) · Endocrinology · doi:10.1210/endo.135.4.7925101 · Cited by 69 · see citing works
Enduring Influences of Peripubertal/Adolescent Stressors on Behavioral Response to Estradiol and Progesterone in Adult Female Mice
Laroche, J., Gasbarro, L., Herman, J. P., & Blaustein, J. D. (2009) · Endocrinology · doi:10.1210/en.2009-0099 · Cited by 65 · see citing works
GATA4 Deficiency Impairs Ovarian Function in Adult Mice1
Kyrönlahti, A., Vetter, M., Euler, R., Bielińska, M., Jay, P. Y., Anttonen, M., Heikinheimo, M., & Wilson, D. B. (2011) · Biology of Reproduction · doi:10.1095/biolreprod.110.086850 · Cited by 63 · see citing works
Chromosomes 6 and 13 Harbor Genes that Regulate Pubertal Timing in Mouse Chromosome Substitution Strains
Krewson, T. D., Supelak, P. J., Hill, A. E., Singer, J. B., Lander, E. S., Nadeau, J. H., & Palmert, M. R. (2004) · Endocrinology · doi:10.1210/en.2004-0543 · Cited by 62 · see citing works
Perinatal androgens organize sex differences in mast cells and attenuate anaphylaxis severity into adulthood
Mackey, E. E., Thelen, K. M., Bali, V., Fardisi, M., Trowbridge, M., Jordan, C. L., & Moeser, A. J. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1915075117 · Cited by 58 · see citing works
Insights into muscle stem cell dynamics during postnatal development
Bachman, J. F., & Chakkalakal, J. V. (2021) · FEBS Journal · doi:10.1111/febs.15856 · Cited by 61 · see citing works
Anabolic androgenic steroids induce age-, sex-, and dose-dependent changes in GABAA receptor subunit mRNAs in the mouse forebrain
McIntyre, K. L., Porter, D. M., & Henderson, L. (2002) · Neuropharmacology · doi:10.1016/s0028-3908(02)00154-5 · Cited by 57 · see citing works
The Impact of Age on the Female Reproductive System
Vidal, J. D. (2016) · Toxicologic Pathology · doi:10.1177/0192623316673754 · Cited by 55 · see citing works
“This is not the case in the mouse, which shows strain-dependent differences in the timing of estrous cyclicity following vaginal opening (Nelson et al. 1990).”
Background
Reproductive Alterations in Chronically Exposed Female Mice to Environmentally Relevant Doses of a Mixture of Phthalates and Alkylphenols
Patiño-García, D., Cruz-Fernandes, L., Buñay, J., et al. (2017) · Endocrinology · doi:10.1210/en.2017-00614 · Cited by 53 · see citing works
“Data of the present work show that chronic exposure to 1 mg/kg/d of phthalates and alkylphenols delays the vaginal opening and first estrous, which are external signs of puberty in female mice (51).”
Background
Practical solutions for including sex as a biological variable (SABV) in preclinical neuropsychopharmacological research
Dalla, C., Jarić, I., Pavlidi, P., Hodes, G. E., Kokras, N., Bespalov, A., Kas, M. J., Steckler, T., Kabbaj, M., Würbel, H., et al. (2023) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2023.110003 · Cited by 50 · see citing works
“It is essential to note that puberty onset timing can vary across rodent species (Bell, 2018) and strains (James et al., 1990) and be influenced by experimental factors such as stress (McCormick et al., 2017) or diet (Tingbei Bo et al., 2021; Engelbregt et al., 2002).”
Background
Delayed puberty and response to testosterone in a rat model of colitis
Azooz, O. G., Farthing, M. J. G., Savage, M. O., et al. (2001) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.2001.281.5.r1483 · Cited by 51 · see citing works
“Vaginal smears from rats with vaginal openings were examined daily, and the onset of vaginal estrus and cycling was determined as described previously (32, 37).”
Method
The influence of puberty on stress reactivity and forebrain glucocorticoid receptor levels in inbred and outbred strains of male and female mice
Romeo, R. D., Kaplowitz, E., Ho, A., & Franco, D. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.07.019 · Cited by 51 · see citing works
“Moreover, despite the variability in pubertal onset between different strains of mice (Nelson et al., 1990), these similar tissue weights at each age across the strains suggests that we sampled our different strains at approximately the same stages of development.”
Background
A mouse model to investigate the impact of testosterone therapy on reproduction in transgender men
Kinnear, H. M., Constance, E. S., David, A., Marsh, E. E., Padmanabhan, V., Shikanov, A., & Moravek, M. B. (2019) · Human Reproduction · doi:10.1093/humrep/dez177 · Cited by 52 · see citing works
“T injection to confirm that the mice were postpubertal and cycling, and subsequently was performed throughout the 6 weeks of T therapy (Nelson et al., 1990).”
Background
Developmental abnormalities in multiple proliferative tissues of ApcMin/+ mice
You, S., Ohmori, M., Peña, M. M. O., Nassri, B., Quiton, J. D., Al-Assaad, Z., Liu, L., Wood, P. A., Berger, S. H., Liu, Z., et al. (2006) · International Journal of Experimental Pathology · doi:10.1111/j.1365-2613.2006.00477.x · Cited by 47 · see citing works
“Puberty begins around the fifth week of life in most inbred mouse strains such as C57BL/6 (Nelson et al. 1990; Joshi et al. 1995).”
Background
Sex differences in the molecular signature of the developing mouse hippocampus
Bundy, J. L., Vied, C., & Nowakowski, R. S. (2017) · BMC Genomics · doi:10.1186/s12864-017-3608-7 · Cited by 50 · see citing works
“ling at approximately 60 days of age [33], therefore 2 month and 4 month (but not 1 month) animals were staged.”
Background
Taste Solution Preferences of C57BL/6J and 129X1/SvJ Mice: Influence of Age, Sex, and Diet
Tordoff, M. G. (2007) · Chemical Senses · doi:10.1093/chemse/bjm034 · Cited by 46 · see citing works
“Mice reach sexual maturity between 3 and 9 weeks (depending on strain and the measure of maturity used, e.g., Nelson et al. 1990).”
Method
Species Comparison of Postnatal Development of the Female Reproductive System
Laffan, S. B., Posobiec, L. M., Uhl, J. E., & Vidal, J. D. (2017) · Birth Defects Research · doi:10.1002/bdr2.1132 · Cited by 44 · see citing works
“Mice have strain dependent differences in the timing of estrous cyclicity following VO (Nelson et al., 1990).”
Background
A study of gender, strain and age differences in mouse liver glutathione-S-transferase
Egaas, E., Falls, J. G., & DAUTERMAN, W. C. (1995) · Comparative Biochemistry and Physiology Part C Pharmacology Toxicology and Endocrinology · doi:10.1016/0742-8413(94)00079-p · Cited by 44 · see citing works
Gender-dependent resiliency to stressful and metabolic challenges following prenatal exposure to high-fat diet in the p66Shc−/− mouse
Bellisario, V., Berry, A., Capoccia, S., Raggi, C., Panetta, P., Branchi, I., Piccaro, G., Giorgio, M., Pelicci, P. G., & Cirulli, F. (2014) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2014.00285 · Cited by 41 · see citing works
“In female mice, VO was determined by daily inspection and recorded as the day on which the vaginal orifice transitioned from tightly closed to patent (Nelson et al., 1990; Azooz et al., 2001; Zhou et al., 2007; Brill and Moenter, 2009).”
MethodInfluential
Adamts18 deletion results in distinct developmental defects and provides a model for congenital disorders of lens, lung, and female reproductive tract development
Ataca, D., Čaikovski, M., Piersigilli, A., et al. (2016) · Biology Open · doi:10.1242/bio.019711 · Cited by 42 · see citing works
“These adjustments were applied to the entire image.”
Method
Contributions of Function-Altering Variants in Genes Implicated in Pubertal Timing and Body Mass for Self-Limited Delayed Puberty
Howard, S. R., Guasti, L., Poliandri, A., David, A., Cabrera, C., Barnes, M. R., Wehkalampi, K., O’Rahilly, S., Aiken, C., Coll, A. P., et al. (2017) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2017-02147 · Cited by 41 · see citing works
“047], an event that reflects the pubertal rise in estradiol (31) (Fig.”
Background
Determination of Reproductive Competence by Confirming Pubertal Onset and Performing a Fertility Assay in Mice and Rats
Hoffmann, H. M. (2018) · Journal of Visualized Experiments · doi:10.3791/58352 · Cited by 43 · see citing works
Fatness rather than leptin sensitivity determines the timing of puberty in female mice
Bohlen, T. M., Silveira, M. A., Zampieri, T. T., Frazão, R., & Donato, J. (2016) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.12.022 · Cited by 40 · see citing works
Acceleration of pubertal development following central blockade of the Y1 subtype of neuropeptide Y receptors
Pralong, F. P., Voirol, M., Giacomini, M., Gaillard, R. C., & Grouzmann, E. (2000) · Regulatory Peptides · doi:10.1016/s0167-0115(00)00130-0 · Cited by 39 · see citing works
In Pursuit of Leucine-Rich Repeat-Containing G Protein-Coupled Receptor-5 Regulation and Function in the Uterus
Sun, X., Jackson, L., Dey, S. K., & Daikoku, T. (2009) · Endocrinology · doi:10.1210/en.2009-0690 · Cited by 40 · see citing works
Minocycline-induced disruption of the intestinal FXR/FGF15 axis impairs osteogenesis in mice
Carson, M. D., Warner, A. J., Hathaway‐Schrader, J. D., Geiser, V. L., Kim, J., Gerasco, J. E., Hill, W., Lemasters, J. J., Alekseyenko, A. V., Wu, Y. R., et al. (2022) · JCI Insight · doi:10.1172/jci.insight.160578 · Cited by 39 · see citing works
“Treatment was initiated at age 6 weeks since C57BL/6 mice typically reach puberty by age 5 to 6 weeks (48).”
The cross‐modal aspect of mouse visual cortex plasticity induced by monocular enucleation is age dependent
Nys, J., Aerts, J., Ytebrouck, E., Vreysen, S., Laeremans, A., & Arckens, L. (2013) · The Journal of Comparative Neurology · doi:10.1002/cne.23455 · Cited by 38 · see citing works
“The age window of puberty and adolescence, between 40 and 100 days in rodents (mouse: Nelson et al., 1990; Lehmann and L€owel, 2008; DiVall et al., 2010; rat: Brenhouse and Andersen, 2011), is often overlooked, yet it is a landmark of visual cortex development because essential synaptic pruning and…”
Background
Colitis causes delay in puberty in female mice out of proportion to changes in leptin and corticosterone
DeBoer, M. D., Li, Y., & Cohn, S. M. (2010) · Journal of Gastroenterology · doi:10.1007/s00535-009-0192-x · Cited by 37 · see citing works
“We followed these mice for the timing of vaginal opening [22, 25]—a welldescribed feature of pubertal progression—as well as for serum levels of leptin and inflammatory cytokines, and colonic inflammation.”
Genetic differences and longevity‐related phenotypes influence lifespan and lifespan variation in a sex‐specific manner in mice
Yuan, R., Musters, C. J. M., Zhu, Y. X., Evans, T. R., Sun, Y., Chesler, E. J., Peters, L. L., Harrison, D. E., & Bartke, A. (2020) · Aging Cell · doi:10.1111/acel.13263 · Cited by 36 · see citing works
“…in the onset of vaginal opening and first vaginal cornification did not parallel those for the onset of cyclicity, indicating that the set of genes specifying the timing of vaginal opening and first vaginal cornification differs from those specifying the onset of cyclicity (Nelson et al., 1990).”
Background
STAT5 signaling in kisspeptin cells regulates the timing of puberty
Silveira, M. A., Furigo, I. C., Zampieri, T. T., Bohlen, T. M., de Paula, D. G., Franci, C. R., Donato, J., & Frazão, R. (2017) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.03.024 · Cited by 35 · see citing works
“As previously reported (Nelson et al., 1990), genetic determinants of onset of cyclicity 484 may differ from those of vaginal opening and first cornification.”
BackgroundMethod
Specific Commensal Bacterium Critically Regulates Gut Microbiota Osteoimmunomodulatory Actions During Normal Postpubertal Skeletal Growth and Maturation
Hathaway‐Schrader, J. D., Poulides, N. A., Carson, M. D., Kirkpatrick, J. E., Warner, A. J., Swanson, B. A., Taylor, E. V., Chew, M. E., Reddy, S. V., Liu, B., et al. (2020) · JBMR Plus · doi:10.1002/jbm4.10338 · Cited by 35 · see citing works
Using three-point bending to evaluate tibia bone strength in ovariectomized young mice
Deckard, C. E., Walker, A., & Hill, B. J. F. (2017) · Journal of Biological Physics · doi:10.1007/s10867-016-9439-y · Cited by 34 · see citing works
“These mice become sexually mature at approximately 6 weeks of age [11], and bone maturity is reached at 16 weeks of age [12–14].”
Background
Daily timing of the adolescent sleep phase: Insights from a cross-species comparison
Hummer, D. L., & Lee, T. M. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.07.023 · Cited by 33 · see citing works
BMP-binding protein twisted gastrulation is required in mammary gland epithelium for normal ductal elongation and myoepithelial compartmentalization
Forsman, C. L., Ng, B., Heinze, R., Kuo, C., Sergi, C. M., Gopalakrishnan, R., Yee, D., Graf, D., Schwertfeger, K. L., & Petryk, A. (2012) · Developmental Biology · doi:10.1016/j.ydbio.2012.10.007 · Cited by 33 · see citing works
“Whole mount hematoxylin and X-Gal staining, elongation and branching analysis Inguinal MGs (#4) were harvested from female mice in early puberty (Nelson et al., 1990) (day of vaginal opening, about six weeks of age).”
The cystic fibrosis transmembrane conductance regulator (Cftr) modulates the timing of puberty in mice
Jin, R., Hodges, C. A., Drumm, M. L., et al. (2006) · Journal of Medical Genetics · doi:10.1136/jmg.2005.032839 · Cited by 33 · see citing works
Central growth hormone signaling is not required for the timing of puberty
Bohlen, T. M., Zampieri, T. T., Furigo, I. C., Teixeira, P. D. S., List, E. O., Kopchick, J. J., Donato, J., & Frazão, R. (2019) · Journal of Endocrinology · doi:10.1530/joe-19-0242 · Cited by 31 · see citing works
A Quantitative Trait Locus on Chromosome 6 Regulates the Onset of Puberty in Mice
Nathan, B. M., Hodges, C. A., Supelak, P. J., Burrage, L. C., Nadeau, J. H., & Palmert, M. R. (2006) · Endocrinology · doi:10.1210/en.2006-0745 · Cited by 31 · see citing works
Adolescent exposure to cocaine, amphetamine, and methylphenidate cross-sensitizes adults to methamphetamine with drug- and sex-specific effects
Shanks, R. A., Ross, J. M., Doyle, H. H., Helton, A., Picou, B. D., Schulz, J., Tavares, C., Bryant, S., Dawson, B. L., & Lloyd, S. A. (2014) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.12.002 · Cited by 29 · see citing works
Asynchronous embryonic germ cell development leads to a heterogeneity of postnatal ovarian follicle activation and may influence the timing of puberty onset in mice
Dai, Y., Bo, Y., Wang, P., Xu, X., Singh, M., Jia, L., Zhang, S., Niu, S., Cheng, K., Liang, J., et al. (2022) · BMC Biology · doi:10.1186/s12915-022-01318-y · Cited by 30 · see citing works
“Since each individual in one inbred strain shares stable genetic background [31, 32], which is like the family study in clinics, our result strongly suggests that the profile of embryonic germ cells development could affect the postnatal puberty onset in humans.”
MethodResultInfluential
Effects of maternal nuclear genome on the timing of puberty in mice offspring
Zhou, Y., Zhu, W., Guo, Z., Zhao, Y., Song, Z., & Xiao, J. (2007) · Journal of Endocrinology · doi:10.1677/joe.1.07049 · Cited by 28 · see citing works
“In order to investigate the potential effects of the maternal genomic background on the timing of puberty in the progeny, two inbred strains of mice (C3H/HeJ and C57BL/6J) were used to produce two pedigrees (direct and reciprocal crosses) because the female individuals differ significantly from each other in the timin…”
MethodInfluential
Sex-specific effects of chronic anabolic androgenic steroid treatment on GABAA receptor expression and function in adolescent mice
Penatti, C. A. A., Porter, D. M., Jones, B., & Henderson, L. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2005.06.041 · Cited by 28 · see citing works
Betacellulin Overexpression in the Mouse Ovary Leads to MAPK3/MAPK1 Hyperactivation and Reduces Litter Size by Impairing Fertilization1
Gratão, A. A., Dahlhoff, M., Sinowatz, F., Wolf, E., & Schneider, M. R. (2007) · Biology of Reproduction · doi:10.1095/biolreprod.107.062588 · Cited by 27 · see citing works
“Importantly, starting with the third cycle, the mean cycle length in both groups was shorter than 6 days in duration, the maximal cycle length considered normal for different mouse strains [24].”
Background
Short-Term High-Fat Diet Increases Leptin Activation of CART Neurons and Advances Puberty in Female Mice
Venancio-Brochi, J. C., Margatho, L. O., Rorato, R. C., Costa, R. R., Debarba, L. K., Coletti, R., Antunes‐Rodrigues, J., Elias, C. F., & Elias, L. L. K. (2017) · Endocrinology · doi:10.1210/en.2017-00452 · Cited by 25 · see citing works
A Short-Day Photoperiod Delays the Timing of Puberty in Female Mice via Changes in the Kisspeptin System
Bohlen, T. M., Silveira, M. A., Buonfiglio, D. D. C., Ferreira‐Neto, H. C., Cipolla‐Neto, J., Donato, J., & Frazão, R. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00044 · Cited by 25 · see citing works
“Sexual maturation was determined by the age at vaginal opening, assessed through the first occurrence of vaginal cornification in the vaginal lavage (first estrus) and the onset of cyclicity, which is the first occurrence of an estrous cycle of typical duration (4–7 days in mice), as previously described (22, 23).”
Method
A battery of olfactory-based screens for phenotyping the social and sexual behaviors of mice
Ferkin, M. H., & Li, H. (2005) · Physiology & Behavior · doi:10.1016/j.physbeh.2005.05.014 · Cited by 24 · see citing works
“Typically, female mice exhibit 4- to 5-day estrous cycles that can be divided into 4 phases—proestrus, estrus, metestrus, and diestrus [6,44,52].”
Background
Brain Region-Specific Regulation of Urocortin 1 Innervation and Corticotropin-Releasing Factor Receptor Type 2 Binding by Ethanol Exposure
Weitemier, A. Z., & Ryabinin, A. E. (2005) · Alcoholism Clinical and Experimental Research · doi:10.1097/01.alc.0000179363.44542.05 · Cited by 24 · see citing works
“Two-way ANOVA detected differences in basal weight between strains, as was shown previously (Nelson et al., 1990) (F1, 41 " 4.”
Method
The last stage of development: The restructuring and plasticity of the cortex during adolescence especially at puberty
Juraska, J. M. (2024) · Developmental Psychobiology · doi:10.1002/dev.22468 · Cited by 29 · see citing works
Partial normalization of pubertal timing in female mice with DSS colitis treated with anti-TNF-α antibody
DeBoer, M. D., Steinman, J. R., & Li, Y. (2012) · Journal of Gastroenterology · doi:10.1007/s00535-012-0542-y · Cited by 22 · see citing works
“While estradiol measurements in mice at pubertal age are at or below the limit of detection even in untreated controls [16], a validated measure of puberty in female mice is the physical examination feature of vaginal opening [9, 20], which occurred earlier in the DSS ? TNF-a ab group compared to the DSS ? Control ab…”
Background
Scientific and Regulatory Policy Committee Best Practices: Documentation of Sexual Maturity by Microscopic Evaluation in Nonclinical Safety Studies
Vidal, J. D., Colman, K. A., Bhaskaran, M., et al. (2021) · Toxicologic Pathology · doi:10.1177/0192623321990631 · Cited by 19 · see citing works
“In mice, the time between vaginal opening and first estrus and the onset of regular cyclicity is inconsistent and may vary across strains or with husbandry practices.(64-66) In female rabbits, the features described for other species do not apply.”
Background
A phenotype for the α7 nicotinic acetylcholine receptor null mutant
Morley, B. J., & Rodriguez‐Sierra, J. F. (2004) · Brain Research · doi:10.1016/j.brainres.2004.07.006 · Cited by 19 · see citing works
Expression patterns of estrogen receptors in the central auditory system change in prepubertal and aged mice
Charitidi, K., Frisina, R. D., Vasilyeva, O. N., Zhu, X., & Canlon, B. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.08.010 · Cited by 19 · see citing works
“N IH -PA Author M anuscript N IH -PA Author M anuscript N IH -PA Author M anuscript they appear in different strains of mice (Nelson et al., 1990).”
Background
Defective Peripheral Nerve Development Is Linked to Abnormal Architecture and Metabolic Activity of Adipose Tissue in Nscl-2 Mutant Mice
Ruschke, K., Ebelt, H., Klöting, N., Boettger, T., Raum, K., Blüher, M., & Braun, T. W. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005516 · Cited by 19 · see citing works
“5 weeks (cyclicity) [22], body fat increased noticeably (Fig.”
Background
Distinct effects of growth hormone deficiency and disruption of hypothalamic kisspeptin system on reproduction of male mice
de Paula, D. G., Bohlen, T. M., Zampieri, T. T., Mansano, N. D. S., Vieira, H. R., Gusmão, D. O., Wasinski, F., Donato, J., & Frazão, R. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.119970 · Cited by 18 · see citing works
Early Marriage and Female Schooling in Bangladesh
Field, E., & Ambrus, A. (2006) · Journal of Political Economy · Cited by 19 · see citing works
Best practices to quantify the impact of reproductive toxicants on development, function, and diseases of the rodent mammary gland
Matouskova, K., Szabo, G. K., Daum, J., et al. (2022) · Reproductive Toxicology · doi:10.1016/j.reprotox.2022.06.011 · Cited by 18 · see citing works
IMMUNOHISTOCHEMICAL, HISTOLOGICAL AND ULTRASTRUCTURAL EVALUATION OF THE EFFECTS OF LEPTIN ON TESTES IN MICE
Kuş, I., Sarsılmaz, M., Canpolat, S., Yılmaz, B., Keleştimur, H., Akpolat, N., & Özoğul, C. (2005) · Archives of Andrology · doi:10.1080/014850190944375 · Cited by 17 · see citing works
“In addition to this primary role, circulating leptin appears to play an important role in the neuroendocrine axis [2], including regulation of reproductive functions [3, 4, 9, 22, 25].”
Background
Comparison of endpoints relevant to toxicity assessments in 3 generations of CD-1 mice fed irradiated natural and purified ingredient diets with varying soy protein and isoflavone contents
Camacho, L., Lewis, S. M., Vanlandingham, M. M., et al. (2016) · Food and Chemical Toxicology · doi:10.1016/j.fct.2016.05.014 · Cited by 16 · see citing works
“All smears in the breeding group for 21 days were read regardless of the time that the first estrus smear was detected and evaluated for cycle parameters; however, the majority of mice did not show regular cycles within this time period, consistent with previous reports that regular cycles in mice can take weeks to be…”
Result
The use of mouse chromosome substitution strains to investigate the genetic regulation of pubertal timing
Nathan, B. M., Hodges, C. A., & Palmert, M. R. (2006) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2006.04.020 · Cited by 16 · see citing works
Experience-dependent regulation of vesicular zinc in male and female 3xTg-AD mice
Nakashima, A. S., Oddo, S., LaFerla, F. M., & Dyck, R. H. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2008.05.028 · Cited by 16 · see citing works
Social and developmental influences on urinary androgen levels in young male white‐faced marmosets (Callithrix geoffroyi)
Birnie, A. K., Smith, A. S., Nali, C., & French, J. A. (2010) · American Journal of Primatology · doi:10.1002/ajp.20909 · Cited by 15 · see citing works
“Genetic influences have been identified that influence the timing of puberty [e.g., mice: Nelson et al., 1990; humans: Townel et al., 2005], and thus such factors should be considered as well.”
Background
Characterization of the onset of leptin effects on the regulation of energy balance
Teixeira, P. D. S., Ramos-Lobo, A. M., Tavares, M. R., Wasinski, F., Frazão, R., & Donato, J. (2021) · Journal of Endocrinology · doi:10.1530/joe-20-0076 · Cited by 15 · see citing works
Ablation of Arginase II Spares Arginine and Abolishes the Arginine Requirement for Growth in Male Mice
Didelija, I. C., Mohammad, M. A., & Marini, J. C. (2017) · Journal of Nutrition · doi:10.3945/jn.117.251249 · Cited by 14 · see citing works
“In C57BL/6 females, this period also coincides with early signs of puberty (vaginal opening; day 28) and onset of vaginal cornification (first day of estrous; day 42) (14).”
Background
The intact immature rodent uterotrophic bioassay: possible effects on assay sensitivity of vomeronasal signals from male rodents and strain differences.
Ashby, J., Owens, W., Odum, J., et al. (2003) · Environmental Health Perspectives · doi:10.1289/ehp.5981 · Cited by 14 · see citing works
“Another factor that may affect the timing of puberty is the strain of animal used (Nelson et al. 1990).”
Background
Onset of sexual maturation in female mice as measured in behavior and fertility: Interactions of exposure to males, phytoestrogen content of diet, and ano-genital distance
Khan, A., Bellefontaine, N., & deCatanzaro, D. (2007) · Physiology & Behavior · doi:10.1016/j.physbeh.2007.10.019 · Cited by 14 · see citing works
Mouse Age Matters: How Age Affects the Murine Plasma Metabolome
Pann, P., de Angelis, M. H., Prehn, C. P., & Adamski, J. (2020) · Metabolites · doi:10.3390/metabo10110472 · Cited by 13 · see citing works
Genetic influences on oestrous cyclicity in mice: evidence that cycle length and frequency are differentially regulated
Nelson, J. F., Karelus, K., Felicio, L. S., & Johnson, T. E. (1992) · Reproduction · doi:10.1530/jrf.0.0940261 · Cited by 13 · see citing works
Self-citation
Three-dimensional quantitative micro-elastography reveals alterations in spatial elasticity patterns in murine ovaries during ageing
Jaeschke, A., Hepburn, M. S., Mowla, A., Kennedy, B. F., & Chan, C. J. (2025) · Communications Biology · doi:10.1038/s42003-025-08835-w · Cited by 13 · see citing works
Postnatal Overnutrition Induces Changes in Synaptic Transmission to Leptin Receptor-Expressing Neurons in the Arcuate Nucleus of Female Mice
Zampieri, T. T., Bohlen, T. M., Silveira, M. A., Lana, L. C., de Paula, D. G., Donato, J., & Frazão, R. (2020) · Nutrients · doi:10.3390/nu12082425 · Cited by 12 · see citing works
“To study pubertal and adult mice, we evaluated sexual maturation, as previously described [25,27,28].”
Method
Med12 regulates ovarian steroidogenesis, uterine development and maternal effects in the mammalian egg†
Wang, X., Mittal, P., Castro, C. A., Rajkovic, G., & Rajkovic, A. (2017) · Biology of Reproduction · doi:10.1093/biolre/iox143 · Cited by 11 · see citing works
“Metestrus stage correlates with decline in estradiol and progesterone levels, and both vaginal cornification and estrous cycle are dependent on circulating estradiol levels [26, 27].”
Background
Prolonged Antibiotic Exposure during Adolescence Dysregulates Liver Metabolism and Promotes Adiposity in Mice
Carson, M. D., Warner, A. J., Geiser, V. L., Hathaway‐Schrader, J. D., Alekseyenko, A. V., Marshall, J. L., Westwater, C., & Novince, C. M. (2023) · American Journal Of Pathology · doi:10.1016/j.ajpath.2023.02.014 · Cited by 10 · see citing works
Addressing Sex as a Biological Variable in Preclinical Models of Lung Disease: An Official American Thoracic Society Research Statement
Lingappan, K., Sundar, I. K., Prakash, Y. S., Redente, E. F., Sin, D. D., Han, M. K., Lahm, T., Krymskaya, V. P., Kotton, D. N., Kulkarni, H. S., et al. (2025) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.202506-1361st · Cited by 10 · see citing works
“In rodents, early markers of puberty are vaginal opening, ﬁ rst vaginal corni ﬁ cation, and the onset of cyclicity in females, whereas balanopreputial separation is used as a marker in males (53).”
Maternal pre-conceptional glyphosate exposure impacts the offspring hepatic and ovarian proteome
Novbatova, G., Timme, K. A., Severin, A., Sayadi, M., & Keating, A. (2023) · Toxicological Sciences · doi:10.1093/toxsci/kfad047 · Cited by 8 · see citing works
“In C57Bl6 mice, vaginal opening was demonstrated to occur at approximately 30 days of age with vaginal cornification and cyclicity being demonstrated at 45 and 60 days, respectively (Nelson et al., 1990).”
Background
A Dominant X-Linked QTL Regulating Pubertal Timing in Mice Found by Whole Genome Scanning and Modified Interval-Specific Congenic Strain Analysis
Zhu, W., Fan, Z., Zhang, C., Guo, Z., Zhao, Y., Zhou, Y., Li, K., Xing, Z., Chen, G., Liang, Y., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003021 · Cited by 8 · see citing works
“05) and the discrepancy was ascribed to genetic factors [6].”
Background
A Pair of Mouse KRAB Zinc Finger Proteins Modulates Multiple Indicators of Female Reproduction1
Krebs, C. J., & Robins, D. M. (2009) · Biology of Reproduction · doi:10.1095/biolreprod.109.080846 · Cited by 8 · see citing works
“timing, VO was examined as a marker of puberty onset [30] in”

HETEROSIS IN CROSSES OF INBRED LINES OF RATS
KIDWELL, J. F., Weeth, H. J., Harvey, W. R., et al. (1960) · Genetics · doi:10.1093/genetics/45.2.225 · Cited by 15 · see citing works
GENETIC AND PHENOTYPIC CHARACTERIZATION OF ROLLER MUTANTS OF CAENORHABDITIS ELEGANS
Cox, G. N., Laufer, J. S., Kusch, M., et al. (1980) · Genetics · doi:10.1093/genetics/95.2.317 · Cited by 128 · see citing works
MUTATIONS WITH DOMINANT EFFECTS ON THE BEHAVIOR AND MORPHOLOGY OF THE NEMATODE CAENORHABDITIS ELEGANS
Park, E.-C., & Horvitz, H. R. (1986) · Genetics · doi:10.1093/genetics/113.4.821 · Cited by 192 · see citing works
`Mass-murder' of ORFs from three regions of chromosome XI from Saccharomyces cerevisiae1Published in conjunction with A Wisconsin Gathering Honoring Waclaw Szybalski on occasion of his 75th year and 20years of Editorship-in-Chief of Gene, 10–11 August 1997, University of Wisconsin, Madison, WI, USA.1
Fairhead, C., Thierry, A., Denis, F., et al. (1998) · Gene · doi:10.1016/s0378-1119(98)00171-1 · Cited by 29 · see citing works
Common homozygosity for predicted loss-of-function variants reveals both redundant and advantageous effects of dispensable human genes
Rausell, A., Luo, Y., Lopez, M., Seeleuthner, Y., Rapaport, F., Favier, A., Stenson, P. D., Cooper, D. N., Patin, É., Casanova, J., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1917993117 · Cited by 36 · see citing works

Authors: Nelson, J. F., Karelus, K., Felicio, L. S., & Johnson, T. E.
Affiliations: McGill University (CA)
The University of Texas at San Antonio (US)
University of Colorado Boulder (US)
Corresponding author: Nelson, James F.
ORCID: Nelson, James F.
Johnson, Thomas E.
Venue: Biology of Reproduction
Publisher: Oxford University Press (OUP)
Published: 1990-04-01
Volume: 42
Issue: 4
Pages: 649-655
ISSN: 0006-3363 (ISSN-L)
1529-7268
DOI: 10.1095/biolreprod42.4.649
OpenAlex: W2026104991
Cited by: 165
References: 0
Citations by year: 2026: 6 · 2025: 11 · 2024: 9 · 2023: 9 · 2022: 12 · 2021: 7 · 2020: 5 · 2019: 8 · 2018: 2 · 2017: 12 · 2016: 9 · 2015: 3 · 2014: 5 · 2013: 3 · 2012: 5
FWCI: 0.90
Type: journal article
Language: en
Open access: closed
Locations: Biology of Reproduction (publishedVersion)
PubMed (publishedVersion)
Funders: Medical Research Council Canada
U.S. Public Health Service
Medical Research Council
National Institute on Aging (AG 08322, AG00369)
Topics: Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
Keywords: pubertal timing, vaginal opening, vaginal cornification, genetic variation, inbred mouse strains, F1 hybrids, heterosis, additive genetic effects, body weight, C57BL/6J mice, DBA/2J, C3H/HeJ
MeSH terms: Age Factors, Animals, Body Weight, Estrus, Female, Genotype, Mice, Inbred Strains, Sexual Maturation, Vagina, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Genetic Influences on the Timing of Puberty in Mice1

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cited by

Related

Record

About these checks