» Articles » PMID: 35121076

Deletion of the Homeodomain Gene Six3 from Kisspeptin Neurons Causes Subfertility in Female Mice

Overview
Authors
Affiliations
Soon will be listed here.
Abstract

The homeodomain transcription factor SIX3 is a known regulator of eye, nose, and forebrain development, and has recently been implicated in female reproduction. Germline heterozygosity of SIX3 is sufficient to cause subfertility, but the cell populations that mediate this role are unknown. The neuropeptide kisspeptin is a critical component of the reproductive axis and plays roles in sexual maturation, ovulation, and the maintenance of gonadotropin secretion. We used Cre-Lox technology to remove Six3 specifically from kisspeptin neurons in mice to test the hypothesis that SIX3 in kisspeptin neurons is required for reproduction. We found that loss of Six3 in kisspeptin neurons causes subfertility and estrous cycle irregularities in females, but no effect in males. Overall, we find that SIX3 expression in kisspeptin neurons is an important contributor to female fertility.

Citing Articles

The homeodomain transcription factor Six3 regulates hypothalamic Pomc expression and its absence from POMC neurons induces hyperphagia and mild obesity in male mice.

Yu H, Chiang A, Rubinstein M, Low M Mol Metab. 2024; 87:101993.

PMID: 39025297 PMC: 11327434. DOI: 10.1016/j.molmet.2024.101993.

References
1.
Atkin S, Owen B, L Bookout A, Cravo R, Lee C, Elias C . Nuclear receptor LRH-1 induces the reproductive neuropeptide kisspeptin in the hypothalamus. Mol Endocrinol. 2013; 27(4):598-605. PMC: 3607696. DOI: 10.1210/me.2012-1371. View

2.
Liu W, Lagutin O, Mende M, Streit A, Oliver G . Six3 activation of Pax6 expression is essential for mammalian lens induction and specification. EMBO J. 2006; 25(22):5383-95. PMC: 1636621. DOI: 10.1038/sj.emboj.7601398. View

3.
Hoffman G, Smith M, Verbalis J . c-Fos and related immediate early gene products as markers of activity in neuroendocrine systems. Front Neuroendocrinol. 1993; 14(3):173-213. DOI: 10.1006/frne.1993.1006. View

4.
Karin M, Liu Z, Zandi E . AP-1 function and regulation. Curr Opin Cell Biol. 1997; 9(2):240-6. DOI: 10.1016/s0955-0674(97)80068-3. View

5.
Lagutin O, Zhu C, Kobayashi D, Topczewski J, Shimamura K, Puelles L . Six3 repression of Wnt signaling in the anterior neuroectoderm is essential for vertebrate forebrain development. Genes Dev. 2003; 17(3):368-79. PMC: 195989. DOI: 10.1101/gad.1059403. View