*Article* **Fetuin-A Inhibits Placental Cell Growth and Ciliogenesis in Gestational Diabetes Mellitus**

#### **Chia-Yih Wang 1,2 , Mei-Tsz Su <sup>3</sup> , Hui-ling Cheng 1,3, Pao-Lin Kuo <sup>3</sup> and Pei-Yin Tsai 3,\***


Received: 9 September 2019; Accepted: 16 October 2019; Published: 21 October 2019

**Abstract:** Gestational diabetes mellitus (GDM) is a type of unbalanced glucose tolerance that occurs during pregnancy, which affects approximately 10% of pregnancies worldwide. Fetuin-A is associated with insulin resistance, and the concentration of circulating fetuin-A increases in women with GDM, however, the role of fetuin-A in the placenta remains unclear. In this study, we enrolled placental samples from twenty pregnant women with GDM and twenty non-GDM pregnant women and found that the abundance of fetuin-A was upregulated in terms of mRNA and protein levels. Fetuin-A inhibited placental cell growth by inducing apoptosis and inhibiting S phase entry. Irregular alignment of mitotic chromosomes and aberrant mitotic spindle poles were observed. In addition, centrosome amplification was induced by fetuin-A treatment, and these amplified centrosomes nucleated microtubules with disorganized microtubule arrays in placental cells. Furthermore, fetuin-A inhibited autophagy, and thus blocked the growth of the primary cilium, a cellular antenna that regulates placenta development and differentiation. Thus, our study uncovered the novel function of fetuin-A in regulating placental cell growth and ciliogenesis.

**Keywords:** fetuin-A; GDM; cell growth; centrosome; primary cilium; autophagy
