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Open AccessArticle

Nitric Oxide Synthase Is Involved in Follicular Development via the PI3K/AKT/FoxO3a Pathway in Neonatal and Immature Rats

1
College of Agriculture and Bio-Engineering, Jinhua Polytechnic, Jinhua 321017, China
2
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China
*
Author to whom correspondence should be addressed.
Animals 2020, 10(2), 248; https://doi.org/10.3390/ani10020248
Received: 22 January 2020 / Revised: 3 February 2020 / Accepted: 4 February 2020 / Published: 5 February 2020
(This article belongs to the Section Animal Reproduction)
It is assumed that nitric oxide synthase and nitric oxide are involved in the regulation of female reproduction. This study aimed to assess the roles of nitric oxide synthase (NOS) in follicular development. The endothelial NOS (eNOS) inhibitor L-NAME, inducible NOS (iNOS) inhibitor S-Methylisothiourea (SMT) and NOS substrate L-arginine (L-Arg) were used in the NOS inhibition models in vivo. Neonatal female rats were treated with phosphate buffer saline (PBS, control), L-NAME (L-NG-Nitroarginine Methyl Ester, 40 mg/kg), SMT (S-Methylisothiourea, 10 mg/kg), L-NAME + SMT, or L-Arg (L-arginine, 50 mg/kg) via subcutaneous (SC) injection on a daily basis for 19 consecutive days, with the samples being collected on specific postnatal days (PD5, PD10, and PD19). The results indicated that the number of antral follicles, the activity of total-NOS, iNOS, neuronal NOS (nNOS), and eNOS, and the content of NO in the ovary were significantly (p < 0.05) increased in the L-Arg group at PD19, while those in L + S group were significantly (p < 0.05) decreased. Meanwhile, the ovarian expression in the L-Arg group in terms of p-AKT, p-FoxO3a, and LC3-II on PD19 were significantly (p < 0.05) upregulated, while the expressions of PTEN and cleaved Caspase-3 were (p < 0.05) downregulated as a result of NOS/NO generation, respectively. Therefore, the results suggest that NOS is possibly involved in the maturation of follicular development to puberty via the PI3K/ AKT/FoxO3a pathway, through follicular autophagia and apoptosis mechanisms.
Keywords: nitric oxide synthase; PTEN; AKT; FoxO3a; follicular development nitric oxide synthase; PTEN; AKT; FoxO3a; follicular development
MDPI and ACS Style

Li, J.; Zhang, W.; Zhu, S.; Shi, F. Nitric Oxide Synthase Is Involved in Follicular Development via the PI3K/AKT/FoxO3a Pathway in Neonatal and Immature Rats. Animals 2020, 10, 248.

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