Table 1.

Effects of MSTN in the female reproductive system

Function			Model	Treatment	Main Results (Ref.)
Ovary	Physiological	Ovarian steroidogenesis	Human granulosa cells	SVOG cells: 30 ng/mL rhMSTN	Steroidogenic acute regulatory ↓ [69]
				hGL cells: recombinant human MSTN	Estradiol production ↑ [72]
					Cytochrome P450 aromatase ↑ [72]
					FSH receptor levels ↑ [72]
					Progesterone production ↓ [72]
					Cell responsiveness to luteinizing hormone ↓ [72]
					LH receptor levels ↓ [72]
			Bovine granulosa cells	Granulosa: MSTN (100 ng/ml)	Basal CYP19A1 expression and estradiol secretion ↑ [73]
					Cell number ↑ [73]
					Basal and FSH-induced HSD3B1 expression and progesterone secretion ↓ [73]
			Bovine theca cells	Theca cells: MSTN (100 ng/ml)	Basal and LH-stimulated androgen secretion ↓ [73]
		Proliferation of granule-cell	Human granulosa cells	SVOG cells: 30 ng/ml recombinant human MSTN	Expression of CTGF ↑ [76]
					Granulosa cell proliferation ↓ [76]
		ECM formation	Human granulosa cells	SVOG cells: MSTN (30 ng/ml)	LOX expression and activity ↑ [86]
				SVOG cells: MSTN (1/10/100 ng/ml)	Secretion of CTGF ↑ [86]
		Oocyte maturation	Porcine oocyte	During the entire IVM of COCs: 1.3 ng/mL MSTN	Mature oocyte quality ↑ [94]
					Modulate phosphorylation of the p38 mitogen-activated protein kinase [94]
					Modulate intracellular glutathione and ROS levels [94]
		COC expansion	Human granulosa cells	SVOG cells: recombinant human MSTN (1/10/ 100 ng/ml)	PTX3 expression and secretion ↓ [68]
	Pathological	OHSS	Human granulosa- lutein cells	hGL cells: MSTN (100 ng/mL)	Aromatase expression ↑ [104]
			Human follicular fluid	OHSS patients' follicular fluid and granulosa cells	MSTN level ↑ [104]
		PCOS	Human	PCOS patients’ granulosa cells	MSTN level ↑ [186]
				PCOS patients’ serum and follicular fluid	MSTN level↑ [127]
Placenta	Physiological	Glucose uptake	Human placental explants	Human term placental explants: MSTN (1 mg/ml)	Deoxyglucose absorption ↑ [146]
			Placental cell lines (BeWo)	BeWo cells: MSTN (0.2 nM /0.4 nM/4 nM /40 nM)	Glucose uptake in Bewo Cells ↓ [152]
		Placenta development	Mice model	MstnLn/Ln mice treated with recombinant MSTN	TNFα concentrations in plasma ↑ [158]
				C2C12 myotubes treated with recombinant MSTN	IL6 expression ↑ [159]
			Human embryonic stem cells	hESC cultured with 20 ng/mL MSTN	Maintain undifferentiated growth of Hes Cells [160]
		Cell invasiveness	Human trophoblasts	EVT and HTR8/SVneo cells cultured with MSTN (25 ng/mL)	Expression and synthesis of FSTL3 ↑ [163]
					Cell invasiveness ↑ [163]
	Pathological	Pre-eclampsia	Human	Pre-eclamptic women’s serum	MSTN in women with pre-eclampsia ↑ [164]
		IUGR	Human	Plasma of Presymptomatic Women	Myostatin dimer in placentae ↑ [168]
		GDM	Human	Serum of women with GDM	Placental FSTL3 in women with GDM ↓ [171]
					Unchanged MSTN Concentration [171]
Uterus	Physiological	Myometrial cell	Pregnant human myometrial 1 cell line	PHM1 cell line supplemented with 1/10 nM MSTN	Myometrial cell growth ↓ [173]
			Human	Adjacent normal myometrium	Activin a and MSTN exert cytostatic activity on healthy myometrial cells [176]
	Pathological	Leiomyoma	Human	Fibroid from women undergoing hysterectomy	Activin a, MSTN, and follistatin-related genes in human leiomyoma ↑ [176]
		Endometriosis	Human	Serum from women with endometriosis	Follistatin level ↑ [183]
		Adenomyosis	Human tissue	Adenomyotic tissues from women undergoing hysterectomy	MSTN, follistatin, and Activin a in adenomyotic tissues ↑ [185]