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Vertebrate reproductive science and technology
RESEARCH ARTICLE

Effect of melatonin on bovine theca cells in vitro

T. Feng A , L. F. Schutz B C , B. C. Morrell B , M. C. Perego B and L. J. Spicer B D
+ Author Affiliations
- Author Affiliations

A Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, Beijing 100097, China.

B Department of Animal Science, Oklahoma State University, Stillwater, OK 74078, USA.

C Present address: College of Pharmacy, Texas A&M Health Science Center, College Station, TX 77843, USA.

D Corresponding author. Email: leon.spicer@okstate.edu

Reproduction, Fertility and Development 30(4) 643-650 https://doi.org/10.1071/RD17203
Submitted: 31 May 2017  Accepted: 11 September 2017   Published: 4 October 2017

Abstract

Melatonin affects granulosa cell function in several species but its function in theca cells is less clear, particularly in monotocous animals. Thus, the objectives of this study were to determine the effects of melatonin on theca cell steroidogenesis, gene expression and cell proliferation in a monotocous species, namely cattle. Ovaries were collected from a local bovine abattoir, from which theca cells were isolated from large (8–22 mm) follicles and treated with various hormones in serum-free medium for 24 h or 48 h. Melatonin caused a dose-dependent inhibition (P < 0.05) of LH+insulin-like growth factor 1 (IGF1)-induced androstenedione and progesterone production. Also, melatonin inhibited (P < 0.05) LH+IGF1-induced expression of steroidogenic acute regulatory protein (StAR) mRNA (via real-time polymerase chain reaction) in theca cells, but it had no effect (P > 0.10) on cytochrome P450 11A1 (CYP11A1) and cytochrome P450 17A1 (CYP17A1) mRNA abundance. In LH+IGF1-treated theca cells, melatonin decreased caspase 3 (CASP3) mRNA to levels similar to those observed in LH-treated theca cells. In contrast, melatonin increased (P < 0.05) the number of bovine theca cells in both LH- and LH+IGF1-treated cultures. In conclusion, melatonin may act as an endocrine regulator of ovarian function in cattle by stimulating theca cell proliferation and inhibiting differentiation via inhibition of hormone-induced steroidogenesis.

Additional keywords: caspase 3, cattle, cytochrome P450 11A1, cytochrome P450 17A1, ovarian follicle, steroidogenesis.


References

Aad, P. Y., Voge, J. L., Santiago, C. A., Malayer, J. R., and Spicer, L. J. (2006). Real-time RT-PCR quantification of pregnancy-associated plasma protein-A mRNA abundance in bovine granulosa and theca cells: effects of hormones in vitro. Domest. Anim. Endocrinol. 31, 357–372.
Real-time RT-PCR quantification of pregnancy-associated plasma protein-A mRNA abundance in bovine granulosa and theca cells: effects of hormones in vitro.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XhtVyit7vI&md5=503741f0900bb60625f6adfd7716f3caCAS |

Aad, P. Y., Echternkamp, S. E., Sypherd, D. D., Schreiber, N. B., and Spicer, L. J. (2012). The hedgehog system in ovarian follicles of cattle selected for twin ovulations and births: evidence of a link between the IGF and hedgehog systems. Biol. Reprod. 87, 79.
The hedgehog system in ovarian follicles of cattle selected for twin ovulations and births: evidence of a link between the IGF and hedgehog systems.Crossref | GoogleScholarGoogle Scholar |

Acuña Castroviejo, D., López, L. C., Escames, G., López, A., García, J. A., and Reiter, R. J. (2011). Melatonin–mitochondria interplay in health and disease. Curr. Top. Med. Chem. 11, 221–240.
Melatonin–mitochondria interplay in health and disease.Crossref | GoogleScholarGoogle Scholar |

Adriaens, I., Jacquet, P., Cortvrindt, R., Janssen, K., and Smitz, J. (2006). Melatonin has dose-dependent effects on folliculogenesis, oocyte maturation capacity and steroidogenesis. Toxicology 228, 333–343.
Melatonin has dose-dependent effects on folliculogenesis, oocyte maturation capacity and steroidogenesis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xht1SgsrzF&md5=d2ec00674bc936a63be9bbb04570e4f4CAS |

Arjmand, F., Khanmohammadi, M., Arasteh, S., Mohammadzadeh, A., Kazemnejad, S., and Akhondi, M. M. (2016). Extended culture of encapsulated human blastocysts in alginate hydrogel containing decidualized endometrial stromal cells in the presence of melatonin. Mol. Biotechnol. 58, 684–694.
Extended culture of encapsulated human blastocysts in alginate hydrogel containing decidualized endometrial stromal cells in the presence of melatonin.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC28XhtlGmsbnE&md5=8e870dc15019013b49d6f57f71f28c5dCAS |

Baburski, A. Z., Sokanovic, S. J., Janjic, M. M., Stojkov-Mimic, N. J., Bjelic, M. M., Andric, S. A., and Kostic, T. S. (2015). Melatonin replacement restores the circadian behavior in adult rat Leydig cells after pinealectomy. Mol. Cell. Endocrinol. 413, 26–35.
Melatonin replacement restores the circadian behavior in adult rat Leydig cells after pinealectomy.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2MXhtV2hsrvM&md5=15bb3c6378881b13bcc8422081dd65d6CAS |

Baltatu, O. C., Amaral, F. G., Campos, L. A., and Cipolla-Neto, J. (2017). Melatonin, mitochondria and hypertension. Cell. Mol. Life Sci , .
Melatonin, mitochondria and hypertension.Crossref | GoogleScholarGoogle Scholar |

Baraño, J. L., and Hammond, J. M. (1985). Serum-free medium enhances growth and differentiation of cultured pig granulosa cells. Endocrinology 116, 51–58.
Serum-free medium enhances growth and differentiation of cultured pig granulosa cells.Crossref | GoogleScholarGoogle Scholar |

Baratta, M., and Tamanini, C. (1992). Effect of melatonin on the in vitro secretion of progesterone and estradiol 17 beta by ovine granulosa cells. Acta Endocrinol. (Copenh.) 127, 366–370.
| 1:CAS:528:DyaK3sXlt1ynsw%3D%3D&md5=55f69b8b6e50ef65715bff26777a95bbCAS |

Beg, M. A., and Ginther, O. J. (2006). Follicle selection in cattle and horses: role of intrafollicular factors. Reproduction 132, 365–377.
Follicle selection in cattle and horses: role of intrafollicular factors.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XhtFCgt77F&md5=3397099ba042b879b19847428eb93955CAS |

Chen, Z., Zuo, X., Li, H., Hong, R., Ding, B., Liu, C., Gao, D., Shang, H., Cao, Z., Huang, W., Zhang, X., and Zhang, Y. (2017). Effects of melatonin on maturation, histone acetylation, autophagy of porcine oocytes and subsequent embryonic development. Anim. Sci. J. 88, 1298–1310.
Effects of melatonin on maturation, histone acetylation, autophagy of porcine oocytes and subsequent embryonic development.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2sXhsV2jsrvK&md5=f4aabfa9db00563671951ca808c4f808CAS |

Clemens, J. W., Jarzynka, M. J., and Witt-Enderby, P. A. (2001). Down-regulation of mt1 melatonin receptors in rat ovary following estrogen exposure. Life Sci. 69, 27–35.
Down-regulation of mt1 melatonin receptors in rat ovary following estrogen exposure.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXktFOqtbs%3D&md5=e24365cfe566d3337657488712d1a3e6CAS |

Dentis, J. L., Schreiber, N. B., Burress, A. M., and Spicer, L. J. (2017). Effects of angiogenin on granulosa and theca cell function in cattle. Animal 11, 811–819.
Effects of angiogenin on granulosa and theca cell function in cattle.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2sXmtFCgt7c%3D&md5=accdec89d8075fa481007e557cee696dCAS |

Feranil, J., Isobe, N., and Nakao, T. (2005). Apoptosis in the antral follicles of swamp buffalo and cattle ovary: TUNEL and caspase-3 histochemistry. Reprod. Domest. Anim. 40, 111–116.
Apoptosis in the antral follicles of swamp buffalo and cattle ovary: TUNEL and caspase-3 histochemistry.Crossref | GoogleScholarGoogle Scholar |

Ferreira, C. S., Carvalho, K. C., Maganhin, C. C., Paiotti, A. P., Oshima, C. T., Simões, M. J., Baracat, E. C., and Soares, J. M. (2016). Does melatonin influence the apoptosis in rat uterus of animals exposed to continuous light? Apoptosis 21, 155–162.
Does melatonin influence the apoptosis in rat uterus of animals exposed to continuous light?Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2MXhvVeqsL3F&md5=b7b37923550106ab1ac7d26fc5c2e0f7CAS |

Fiske, V. M., Parker, K. L., Ulmer, R. A., Ow, C. H., and Aziz, N. (1984). Effect of melatonin alone or in combination with human chorionic gonadotropin or ovine luteinizing hormone on the in vitro secretion of estrogens or progesterone by granulosa cells of rats. Endocrinology 114, 407–410.
Effect of melatonin alone or in combination with human chorionic gonadotropin or ovine luteinizing hormone on the in vitro secretion of estrogens or progesterone by granulosa cells of rats.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL2cXpslWmuw%3D%3D&md5=94d71c803d63b66f68fca5cce243a550CAS |

Friedrich, A., Pechstein, J., Berens, C., and Lührmann, A. (2017). Modulation of host cell apoptotic pathways by intracellular pathogens. Curr. Opin. Microbiol. 35, 88–99.
Modulation of host cell apoptotic pathways by intracellular pathogens.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2sXjvF2gt7k%3D&md5=1a605e0903dead159540340cb7209a3bCAS |

Grado-Ahuir, J. A., Aad, P. Y., and Spicer, L. J. (2011). New insights into the pathogenesis of cystic follicles in cattle: microarray analysis of gene expression in granulosa cells. J. Anim. Sci. 89, 1769–1786.
New insights into the pathogenesis of cystic follicles in cattle: microarray analysis of gene expression in granulosa cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXnsVWkt7w%3D&md5=d208ce8fb2a56587860a72be6e38c4a2CAS |

He, Y., Deng, H., Jiang, Z., Li, Q., Shi, M., Chen, H., and Han, Z. (2016a). Effects of melatonin on follicular atresia and granulosa cell apoptosis in the porcine. Mol. Reprod. Dev. 83, 692–700.
Effects of melatonin on follicular atresia and granulosa cell apoptosis in the porcine.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC28XhtF2mt77F&md5=0d79101d7f8145f294e14cf87bffff4fCAS |

He, Y. M., Deng, H. H., Shi, M. H., Bodinga, B. M., Chen, H. L., Han, Z. S., Jiang, Z. L., and Li, Q. W. (2016b). Melatonin modulates the functions of porcine granulosa cells via its membrane receptor MT2 in vitro. Anim. Reprod. Sci. 172, 164–172.
Melatonin modulates the functions of porcine granulosa cells via its membrane receptor MT2 in vitro.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC28Xht12jt7rN&md5=8f2d9248c8433ac02a9561fd8b1d8577CAS |

He, C., Ma, T., Shi, J., Zhang, Z., Wang, J., Zhu, K., Li, Y., Yang, M., Song, Y., and Liu, G. (2016c). Melatonin and its receptor MT1 are involved in the downstream reaction to luteinizing hormone and participate in the regulation of luteinization in different species. J. Pineal Res. 61, 279–290.
Melatonin and its receptor MT1 are involved in the downstream reaction to luteinizing hormone and participate in the regulation of luteinization in different species.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC28XhtVyntLvK&md5=6f5e767fa91b60baf86195ce034e9634CAS |

Hu, J. J., Zhang, X. Y., Zhang, Y., Zhao, X. X., Li, F. D., and Tao, J. Z. (2017). Molecular characterization and expression profile of the melatonin receptor MT1 in the ovary of Tianzhu white yak (Bos grunniens). Gen. Comp. Endocrinol. 242, 101–107.
Molecular characterization and expression profile of the melatonin receptor MT1 in the ovary of Tianzhu white yak (Bos grunniens).Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2MXhslGltbnF&md5=3c51df9393745eeaad119573d2f986f7CAS |

Ishido, M. (2004). Transient inhibition of synergistically insulin-like growth factor-1- and bisphenol A-induced proliferation of estrogen receptor alpha (ERalpha)-positive human breast cancer MCF-7 cells by melatonin. Environ. Sci. 11, 163–170.
| 1:CAS:528:DC%2BD2cXmt1OnsLo%3D&md5=38d239599c0e949c4b616141e5084629CAS |

Ishizuka, B., Kuribayashi, Y., Murai, K., Amemiya, A., and Itoh, M. T. (2000). The effect of melatonin on in vitro fertilization and embryo development in mice. J. Pineal Res. 28, 48–51.
The effect of melatonin on in vitro fertilization and embryo development in mice.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXis1Ogtw%3D%3D&md5=b73f4173550e72cc1b99023bea7158bcCAS |

Kang, J. T., Koo, O. J., Kwon, D. K., Park, H. J., Jang, G., Kang, S. K., and Lee, B. C. (2009). Effects of melatonin on in vitro maturation of porcine oocyte and expression of melatonin receptor RNA in cumulus and granulosa cells. J. Pineal Res. 46, 22–28.
Effects of melatonin on in vitro maturation of porcine oocyte and expression of melatonin receptor RNA in cumulus and granulosa cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXlsV2rtQ%3D%3D&md5=46f93934abb79891ac558ce9cb3532eaCAS |

Lagaly, D. V., Aad, P. Y., Grado-Ahuir, J. A., Hulsey, L. B., and Spicer, L. J. (2008). Role of adiponectin in regulating ovarian granulosa and theca cell function. Mol. Cell. Endocrinol. 284, 38–45.
Role of adiponectin in regulating ovarian granulosa and theca cell function.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXislSlt7Y%3D&md5=80b5cd168cbe23f1d359432f168d452fCAS |

Langhout, D. J., Spicer, L. J., and Geisert, R. D. (1991). Development of a culture system for bovine granulosa cells: effects of growth hormone, estradiol, and gonadotropins on cell proliferation, steroidogenesis, and protein synthesis. J. Anim. Sci. 69, 3321–3334.
Development of a culture system for bovine granulosa cells: effects of growth hormone, estradiol, and gonadotropins on cell proliferation, steroidogenesis, and protein synthesis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3MXlslGju7Y%3D&md5=cee0052da2304a080dae35d7aca96dd1CAS |

Lee, C. J., Do, B. R., Lee, Y. H., Park, J. H., Kim, S. J., Kim, J. K., Roh, S. I., Yoon, Y. D., and Yoon, H. S. (2001). Ovarian expression of melatonin Mel(1a) receptor mRNA during mouse development. Mol. Reprod. Dev. 59, 126–132.
Ovarian expression of melatonin Mel(1a) receptor mRNA during mouse development.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXjsVals74%3D&md5=9af3c790d4315f898ebc7bcaeb4abf0cCAS |

Li, C., and Zhou, X. (2015). Melatonin and male reproduction. Clin. Chim. Acta 446, 175–180.
Melatonin and male reproduction.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2MXnslKqurc%3D&md5=da79e70541e5982627b58ae8222e665dCAS |

Lima, G. N., Maganhin, C. C., Simões, R. S., Baracat, M. C., Sasso, G. R., Fuchs, L. F., Simões Mde, J., Baracat, E. C., and Soares Júnior, J. M. (2015). Steroidogenesis-related gene expression in the rat ovary exposed to melatonin supplementation. Clinics (Sao Paulo) 70, 144–151.
Steroidogenesis-related gene expression in the rat ovary exposed to melatonin supplementation.Crossref | GoogleScholarGoogle Scholar |

Maganhin, C. C., Fuchs, L. F., Simões, R. S., Oliveira-Filho, R. M., de Jesus Simões, M., Baracat, E. C., and Soares, J. M. (2013). Effects of melatonin on ovarian follicles. Eur. J. Obstet. Gynecol. Reprod. Biol. 166, 178–184.
Effects of melatonin on ovarian follicles.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhsFKnsb%2FP&md5=c897f3aeff30a80d1789cd6951b87743CAS |

Maganhin, C. C., Simões, R. S., Fuchs, L. F., Sasso, G. R., Simões, M. J., Baracat, E. C., and Soares, J. M. (2014). Melatonin influences on steroidogenic gene expression in the ovary of pinealectomized rats. Fertil. Steril. 102, 291–298.
Melatonin influences on steroidogenic gene expression in the ovary of pinealectomized rats.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXotFOkt74%3D&md5=ecee45446010a1c4f874b17e4e441bb5CAS |

Magoffin, D. A., Kurtz, K. M., and Erickson, G. F. (1990). Insulin-like growth factor-I selectively stimulates cholesterol side-chain cleavage expression in ovarian theca-interstitial cells. Mol. Endocrinol. 4, 489–496.
Insulin-like growth factor-I selectively stimulates cholesterol side-chain cleavage expression in ovarian theca-interstitial cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3cXitlSgsL0%3D&md5=670e072211a4e961877884a2cce40fc4CAS |

Manabe, N., Goto, Y., Matsuda-Minehata, F., Inoue, N., Maeda, A., Sakamaki, K., and Miyano, T. (2004). Regulation mechanism of selective atresia in porcine follicles: regulation of granulosa cell apoptosis during atresia. J. Reprod. Dev. 50, 493–514.
Regulation mechanism of selective atresia in porcine follicles: regulation of granulosa cell apoptosis during atresia.Crossref | GoogleScholarGoogle Scholar |

Mayo, J. C., Sainz, R. M., Antoli, I., Herrera, F., Martin, V., and Rodriguez, C. (2002). Melatonin regulation of antioxidant enzyme gene expression. Cell. Mol. Life Sci. 59, 1706–1713.
Melatonin regulation of antioxidant enzyme gene expression.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XovVOnurs%3D&md5=b6da67b7c61633a39492deec6cb5e99fCAS |

McNatty, K. P., Hudson, N., Gibb, M., Henderson, K. M., Lun, S., Heath, D., and Montgomery, G. W. (1984). Seasonal differences in ovarian activity in cows. J. Endocrinol. 102, 189–198.
Seasonal differences in ovarian activity in cows.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL2cXks1Kntrc%3D&md5=ca3e7dedb33b8e12f9e295c4dafbe1f2CAS |

Nagina, G., Asima, A., Nemat, U., and Shamim, A. (2016). Effect of melatonin on maturation capacity and fertilization of Nili-Ravi buffalo (Bubalus bubalis) oocytes. Open Vet. J. 6, 128–134.
Effect of melatonin on maturation capacity and fertilization of Nili-Ravi buffalo (Bubalus bubalis) oocytes.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BC2szisVOmsg%3D%3D&md5=b41b42b21e356813631501952fa90a04CAS |

Nakamura, E., Otsuka, F., Terasaka, T., Inagaki, K., Hosoya, T., Tsukamoto-Yamauchi, N., Toma, K., and Makino, H. (2014). Melatonin counteracts BMP-6 regulation of steroidogenesis by rat granulosa cells. J. Steroid Biochem. Mol. Biol. 143, 233–239.
Melatonin counteracts BMP-6 regulation of steroidogenesis by rat granulosa cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXhsVaksrbJ&md5=5512a007c34de89c2fbb6f511738a5ecCAS |

Ott, L. (1977). Multiple comparisons. In ‘An Introduction to Statistical Methods and Data Analysis’. (Ed. C. Beal.) pp. 384–388. (Duxbury Press: North Scituate, MA, USA.)

Persengiev, S., and Kehajova, J. (1991). Inhibitory action of melatonin and structurally related compounds on testosterone production by mouse Leydig cells in vitro. Cell Biochem. Funct. 9, 281–286.
Inhibitory action of melatonin and structurally related compounds on testosterone production by mouse Leydig cells in vitro.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK38XjsV2jtQ%3D%3D&md5=a7e0016da5b8102b1cd2576ee2a6659eCAS |

Qin, F., Zhang, J., Zan, L., Guo, W., Wang, J., Chen, L., Cao, Y., Shen, O., and Tong, J. (2015). Inhibitory effect of melatonin on testosterone synthesis is mediated via GATA-4/SF-1 transcription factors. Reprod. Biomed. Online 31, 638–646.
Inhibitory effect of melatonin on testosterone synthesis is mediated via GATA-4/SF-1 transcription factors.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2MXhtlWgtrbP&md5=f78349a8754a537fe1d6bda2e6f6467fCAS |

Roberts, A. J., and Skinner, M. K. (1990). Estrogen regulation of theca cell steroidogenesis and differentiation: theca cell-granulosa cell interactions. Endocrinology 127, 2918–2929.
Estrogen regulation of theca cell steroidogenesis and differentiation: theca cell-granulosa cell interactions.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3MXhslOhtQ%3D%3D&md5=1ebcebdfb2ceef636200c38321a6ecfaCAS |

Sánchez, A., Calpena, A. C., and Clares, B. (2015). Evaluating the oxidative stress in inflammation: role of melatonin. Int. J. Mol. Sci. 16, 16981–17004.
Evaluating the oxidative stress in inflammation: role of melatonin.Crossref | GoogleScholarGoogle Scholar |

Schreiber, N. B., Totty, M. L., and Spicer, L. J. (2012). Expression and effect of fibroblast growth factor 9 in bovine theca cells. J. Endocrinol. 215, 167–175.
Expression and effect of fibroblast growth factor 9 in bovine theca cells.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BC38fmtlegug%3D%3D&md5=a67a102102d3683e7d9ee6ecc42dca4dCAS |

Shi, L., Li, N., Bo, L., and Xu, Z. (2013). Melatonin and hypothalamic–pituitary–gonadal axis. Curr. Med. Chem. 20, 2017–2031.
Melatonin and hypothalamic–pituitary–gonadal axis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXotl2is7Y%3D&md5=403015d05ee44fc9ea335b93221dc921CAS |

Sirotkin, A. V. (1994). Direct influence of melatonin on steroid, nonapeptide hormones, and cyclic nucleotide secretion by granulosa cells isolated from porcine ovaries. J. Pineal Res. 17, 112–117.
Direct influence of melatonin on steroid, nonapeptide hormones, and cyclic nucleotide secretion by granulosa cells isolated from porcine ovaries.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2MXivV2ns7g%3D&md5=e132fac0a5096594b60af86fab03159fCAS |

Soares, J. M., Simões, M. J., Oshima, C. T., Mora, O. A., De Lima, G. R., and Baracat, E. C. (2003). Pinealectomy changes rat ovarian interstitial cell morphology and decreases progesterone receptor expression. Gynecol. Endocrinol. 17, 115–123.
Pinealectomy changes rat ovarian interstitial cell morphology and decreases progesterone receptor expression.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXktFKisbY%3D&md5=1fc6b76a41724e3ab1224c04cd65a238CAS |

Spicer, L. J., and Aad, P. Y. (2007). Insulin-like growth factor (IGF) 2 stimulates steroidogenesis and mitosis of bovine granulosa cells through the IGF1 receptor: role of follicle-stimulating hormone and IGF2 receptor. Biol. Reprod. 77, 18–27.
Insulin-like growth factor (IGF) 2 stimulates steroidogenesis and mitosis of bovine granulosa cells through the IGF1 receptor: role of follicle-stimulating hormone and IGF2 receptor.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXntV2gsbo%3D&md5=8b42864d00691c989dc2ec140b854cd1CAS |

Spicer, L. J., and Chamberlain, C. S. (1998). Influence of cortisol on insulin- and insulin-like growth factor 1 (IGF-1)-induced steroid production and on IGF-1 receptors in cultured bovine granulosa cells and thecal cells. Endocrine 9, 153–161.
Influence of cortisol on insulin- and insulin-like growth factor 1 (IGF-1)-induced steroid production and on IGF-1 receptors in cultured bovine granulosa cells and thecal cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXnsVSjtro%3D&md5=044fafc71c11a6723385247cb2340356CAS |

Spicer, L. J., and Stewart, R. E. (1996). Interaction among bovine somatotropin, insulin and gonadotropins on steroid production by bovine granulosa and theca cells. J. Dairy Sci. 79, 813–821.
Interaction among bovine somatotropin, insulin and gonadotropins on steroid production by bovine granulosa and theca cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK28XktVWkurY%3D&md5=140573ee21ca4a2ab275794f5837d0bfCAS |

Spicer, L. J., Leung, K., Convey, E. M., Gunther, J., Short, R. E., and Tucker, H. A. (1986). Anovulation in postpartum suckled beef-cows. 1. Associations among size and numbers of ovarian follicles, uterine involution, and hormones in serum and follicular-fluid. J. Anim. Sci. 62, 734–741.
Anovulation in postpartum suckled beef-cows. 1. Associations among size and numbers of ovarian follicles, uterine involution, and hormones in serum and follicular-fluid.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL28XitVWjt7k%3D&md5=ec785b53ce7f5d84cdc9814c1ceec05fCAS |

Spicer, L. J., Aad, P. Y., Allen, D. T., Mazerbourg, S., Payne, A. H., and Hsueh, A. J. (2008). Growth differentiation factor 9 (GDF9) stimulates proliferation and inhibits steroidogenesis by bovine theca cells: influence of follicle size on responses to GDF9. Biol. Reprod. 78, 243–253.
Growth differentiation factor 9 (GDF9) stimulates proliferation and inhibits steroidogenesis by bovine theca cells: influence of follicle size on responses to GDF9.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXht1Kru7o%3D&md5=121b347cf1c0a9cac0518acc7eccae42CAS |

Spicer, L. J., Schreiber, N. B., Lagaly, D. V., Aad, P. Y., Douthit, L. B., and Grado-Ahuir, J. A. (2011). Effect of resistin on granulosa and theca cell function in cattle. Anim. Reprod. Sci. 124, 19–27.
Effect of resistin on granulosa and theca cell function in cattle.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXjvVyjsrs%3D&md5=09cf43aa6516f788db3e973f2c0d709eCAS |

Srivastava, R. K., and Krishna, A. (2010). Melatonin affects steroidogenesis and delayed ovulation during winter in vespertilionid bat, Scotophilus heathi. J. Steroid Biochem. Mol. Biol. 118, 107–116.
Melatonin affects steroidogenesis and delayed ovulation during winter in vespertilionid bat, Scotophilus heathi.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhs1Wks7fP&md5=5939a1c0ec18ef9de51f038801fdee43CAS |

Stewart, R. E., Spicer, L. J., Hamilton, T. D., and Keefer, B. E. (1995). Effects of insulin-like growth factor I and insulin on proliferation and on basal and luteinizing hormone-induced steroidogenesis of bovine thecal cells; involvement of glucose and receptors for insulin-like growth factor I and luteinizing hormone. J. Anim. Sci. 73, 3719–3731.
Effects of insulin-like growth factor I and insulin on proliferation and on basal and luteinizing hormone-induced steroidogenesis of bovine thecal cells; involvement of glucose and receptors for insulin-like growth factor I and luteinizing hormone.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK28XptFWgtg%3D%3D&md5=ef3472a713ad86b4a6aa6e6173960a8bCAS |

Stewart, R. E., Spicer, L. J., Hamilton, T. D., Keefer, B. E., Dawson, L. J., Morgan, G. L., and Echternkamp, S. E. (1996). Levels of insulin-like growth factor (IGF) binding proteins, luteinizing hormone and IGF-I receptors, and steroids in dominant follicles during the first follicular wave in cattle exhibiting regular estrous cycles. Endocrinology 137, 2842–2850.
Levels of insulin-like growth factor (IGF) binding proteins, luteinizing hormone and IGF-I receptors, and steroids in dominant follicles during the first follicular wave in cattle exhibiting regular estrous cycles.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK28XjvVWjtrY%3D&md5=56298274ec04a22cb4371f52bce687d8CAS |

Sundaresan, N. R., Marcus Leo, M. D., Subramani, J., Anish, D., Sudhagar, M., Ahmed, K. A., Saxena, M., Tyagi, J. S., Sastry, K. V., and Saxena, V. K. (2009). Expression analysis of melatonin receptor subtypes in the ovary of domestic chicken. Vet. Res. Commun. 33, 49–56.
Expression analysis of melatonin receptor subtypes in the ovary of domestic chicken.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD1M%2Fksl2ksw%3D%3D&md5=76cf294c4cfb4e795df1d842aaa7f85bCAS |

Tamura, H., Nakamura, Y., Takiguchi, S., Kashida, S., Yamagata, Y., Sugino, N., and Kato, H. (1998). Melatonin directly suppresses steroid production by preovulatory follicles in the cyclic hamster. J. Pineal Res. 25, 135–141.
Melatonin directly suppresses steroid production by preovulatory follicles in the cyclic hamster.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXmtlCrsrc%3D&md5=4276601cc3028cf1dbca00d0f026275fCAS |

Tan, D. X., Manchester, L. C., Liu, X., Rosales-Corral, S. A., Acuna-Castroviejo, D., and Reiter, R. J. (2013). Mitochondria and chloroplasts as the original sites of melatonin synthesis: a hypothesis related to melatonin’s primary function and evolution in eukaryotes. J. Pineal Res. 54, 127–138.
Mitochondria and chloroplasts as the original sites of melatonin synthesis: a hypothesis related to melatonin’s primary function and evolution in eukaryotes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXjtVCqs78%3D&md5=37d45cbfa1924901fc2691892b221da6CAS |

Tanabe, M., Tamura, H., Taketani, T., Okada, M., Lee, L., Tamura, I., Maekawa, R., Asada, H., Yamagata, Y., and Sugino, N. (2015). Melatonin protects the integrity of granulosa cells by reducing oxidative stress in nuclei, mitochondria, and plasma membranes in mice. J. Reprod. Dev. 61, 35–41.
Melatonin protects the integrity of granulosa cells by reducing oxidative stress in nuclei, mitochondria, and plasma membranes in mice.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2MXlslKkurc%3D&md5=76a572538d91094dcf5abf1eb132d7c2CAS |

Tanavde, V. S., and Maitra, A. (2003). In vitro modulation of steroidogenesis and gene expression by melatonin: a study with porcine antral follicles. Endocr. Res. 29, 399–410.
In vitro modulation of steroidogenesis and gene expression by melatonin: a study with porcine antral follicles.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXovVOnsLg%3D&md5=dfc8c2ce8e12c238405b38747366de73CAS |

Tian, X., Wang, F., He, C., Zhang, L., Tan, D., Reiter, R. J., Xu, J., Ji, P., and Liu, G. (2014). Beneficial effects of melatonin on bovine oocytes maturation: a mechanistic approach. J. Pineal Res. 57, 239–247.
Beneficial effects of melatonin on bovine oocytes maturation: a mechanistic approach.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXhsF2ntbjE&md5=d492feccb6262f6c7dbf608672b87c8cCAS |

Tian, X., Wang, F., Zhang, L., He, C., Ji, P., Wang, J., Zhang, Z., Lv, D., Abulizi, W., Wang, X., Lian, Z., and Liu, G. (2017). Beneficial effects of melatonin on the in vitro maturation of sheep oocytes and its relation to melatonin receptors. Int. J. Mol. Sci. 18, 834.
Beneficial effects of melatonin on the in vitro maturation of sheep oocytes and its relation to melatonin receptors.Crossref | GoogleScholarGoogle Scholar |

Unfer, V., Raffone, E., Rizzo, P., and Buffo, S. (2011). Effect of a supplementation with myo-inositol plus melatonin on oocyte quality in women who failed to conceive in previous in vitro fertilization cycles for poor oocyte quality: a prospective, longitudinal, cohort study. Gynecol. Endocrinol. 27, 857–861.
Effect of a supplementation with myo-inositol plus melatonin on oocyte quality in women who failed to conceive in previous in vitro fertilization cycles for poor oocyte quality: a prospective, longitudinal, cohort study.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhtlWmsrfK&md5=70ccb537fc5d80f6f10c7d304ab7af17CAS |

Varoni, E. M., Soru, C., Pluchino, R., Intra, C., and Iriti, M. (2016). The impact of melatonin in research. Molecules 21, 240.
The impact of melatonin in research.Crossref | GoogleScholarGoogle Scholar |

Voge, J. L., Aad, P. Y., Santiago, C. A., Goad, D. W., Malayer, J. R., Allen, D., and Spicer, L. J. (2004). Effect of insulin-like growth factors (IGF), FSH, and leptin on IGF-binding-protein mRNA expression in bovine granulosa and theca cells: quantitative detection by real-time PCR. Peptides 25, 2195–2203.
Effect of insulin-like growth factors (IGF), FSH, and leptin on IGF-binding-protein mRNA expression in bovine granulosa and theca cells: quantitative detection by real-time PCR.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXhtValsr3F&md5=b522a796adb9c00bfbad6998d427a1beCAS |

Voiculescu, S. E., Zygouropoulos, N., Zahiu, C. D., and Zagrean, A. M. (2014). Role of melatonin in embryo fetal development. J. Med. Life 7, 488–492.
| 1:STN:280:DC%2BC2Mjis1Krtg%3D%3D&md5=f87e27b0cb6a8a8f7951ec951d2b05f6CAS |

Vriend, J., and Reiter, R. J. (2015). Melatonin feedback on clock genes: a theory involving the proteasome. J. Pineal Res. 58, 1–11.
Melatonin feedback on clock genes: a theory involving the proteasome.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXitFSitL7N&md5=ec86a7f438059f77b1f1ea07da8bd7daCAS |

Wang, S. J., Liu, W. J., Wu, C. J., Ma, F. H., Ahmad, S., Liu, B. R., Han, L., Jiang, X. P., Zhang, S. J., and Yang, L. G. (2012). Melatonin suppresses apoptosis and stimulates progesterone production by bovine granulosa cells via its receptors (MT1 and MT2). Theriogenology 78, 1517–1526.
Melatonin suppresses apoptosis and stimulates progesterone production by bovine granulosa cells via its receptors (MT1 and MT2).Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhtlGntr7I&md5=e9a9f7be0cedede806818bc8d6ec74ddCAS |

Webley, G. E., and Luck, M. R. (1986). Melatonin directly stimulates the secretion of progesterone by human and bovine granulosa cells in vitro. J. Reprod. Fertil. 78, 711–717.
Melatonin directly stimulates the secretion of progesterone by human and bovine granulosa cells in vitro.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL2sXhtlertw%3D%3D&md5=4479b6599645e1407e5ddbcd7d018156CAS |

Zhang, L., Schütz, L. F., Robinson, C. L., Totty, M. L., and Spicer, L. J. (2017). Evidence that gene expression of ovarian follicular tight junction proteins is regulated in vivo and in vitro in cattle. J. Anim. Sci. 95, 1313–1324.
Evidence that gene expression of ovarian follicular tight junction proteins is regulated in vivo and in vitro in cattle.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2sXhtV2jtbjN&md5=e6298a03a16684a2470e25271cc0e87eCAS |