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Table 2 Postnatally galactose-induced animal models for POI

From: Induced premature ovarian insufficiency by using D galactose and its effects on reproductive profiles in small laboratory animals: a systematic review

Author, year (Refs.)

Strain & treatment

Age at treatment in group (s) & (age of sampling)

Results

Ovarian morphological histology

Appearance changes

Hormonal profile

Estrus cycle, vaginal opening

Body weight

Metabolic disturbances

Swartz et al., 1988 [26]

White mice, feeding by 50% galactose, superovulation by HMG, and HCG

6 weeks, Grp1:feeding by galactose for two weeks (8 weeks)

Grp 2: feeding by galactose for four weeks (10 weeks)

Grp 3: feeding by galactose for six weeks (12 weeks)

Grp 4: Feeding for 2,4, and 6 weeks, then superovulation (the day after treatment)

Grp 5: Feeding for 7 weeks, then regular standard feeding for 1 week, then super-ovulation (the day after treatment) (Adv)

Grp1,2,3: CL↓

Grp 4: CL↓, ovulatory response ↓

Grp 5: ovulatory response (NC)

NR

NR (Lim)

NR (Lim)

Grp 1,2,3,5↓

Grp 4: NR

NR

Yan z et al. 2018 [27]

C57BL/6 female mice, aged, subcutaneously injected D galactose 200 mg/kg/day for 42 days,

7–8 weeks (after 42 days intervention)

PMF ↓

AGC ↑

NR

FSH↑

LH↑

E2↓

P↓

AMH mRNA expression ↓ (ADV)

NR (Lim)

NR

NR

Zhang et al. 2016 [28]

KM mice, (age?) feeding 35% galactose, for 70 days

PND?,(Lim) (70 days after feeding)

OO (NEC)

GC (APOP)↑

CL↓

No mature oocyte in antral follicles

No abnormality in uterus

No obvious pathological change in ovary

FSH↓

LH (NSD)

E2 (NSD)

NR (Lim)

GR↓

BW↓

GAL↑

Alb↑

TP↑

Zhang et al. 2017 [29]

ICR F1 hybrids, 12–14 days, preantral follicle culture, 5 mg/ml D-galactose. Culture and in vitro

Only preantral follicles with two layers of granulosa cells (100–130 μm) with intact basal membrane and some theca cells

Inhibit follicle development it does not exhibit obvious follicular toxicity at day 2 of culture, the influence of D-galactose on oocyte maturation is relatively weak

NR

NR (Lim)

NR (Lim)

NR

NR

Meyer et al. 1992 [30]

SD rat, feeding by 40% galactose

Pre pubertal,PND 21–24, (immediately after weaning)

ovulation ↓

granulosa cells↓

NR

NR (Lim)

NR

Body weight↓

Ovary weight↓

Ovarian Galactitol concentration↑

Ahangarpour et al. 2016 [31]

NMRI mice, injected subcutaneously with D-galactose 500 mg/kg/d for 45 days) and concomitantly administered

normal saline by gavage twice daily for the last 7 days

3 months (after 45 days treatment)

No Graafian follicles

No zona pellucida

Atrophy of the endometrium

LH↑

FSH↑

E2↓ progesterone↓

Disrupt the estrous cycle

Body weight↑

Ovary and uterus -weight/body weight↓

NR

Wang et al. 2018 [32]

Kunming white mice, Daily ip. Injection of 200 mg/kg D-galactose (dissolved in saline, 0.2 ml/mouse/day) for 50 days, and between the 21st to 50th day of D-galactose injections, the group also received 0.5% CMC-Na solution (0.3 ml/mouse/day) by gavage.

Six to eight week-old (the end of 50 days treatment)

No mature follicles

More atretic follicles

Reduced follicle numbers

Smaller follicles

Diameter of ovarian follicles at all stages ↓

Proportion of secondary follicles ↑

The number of interna theca cells in tertiary follicles ↓

The number of externa theca cells in tertiary follicles ↑

NR

FSH↑

LH↑

AMH↓

E2↓

NR (Lim)

NR (Lim)

NR

Liu et al. 2005 [33]

Long-Evans rats, High lactose diet (HLD),41.9 g Lactose

Ovaries morphology at 2 months of age for baseline, seven months later for intervention outcomes

25-days-old, (7 month later)

No significant differences in the number of primordial, growing, and antral follicles

 

Progesterone ↓

Estradiol (NC)

Irregular EC from 5 months of age

Body weight ↓

Increased fresh ovary weight (+)

NR

Liu et al. 2006 [34]

Long-Evans rats, 20% galactose diet,

21-day-old,(PND 40)

Growing and antral follicles ↓

Primordial NC

Atretic NC

Non growing follicles ↑

NR (Lim)

no significant changes in the serum concentrations of estradiol and progesterone

The study has done before the first spontaneous ovulation (ADV)

Body weight (NC)

Ovaries w (NC)

Uterus weight ↓

NR

Lai et al. 2003 [35]

SD, Feeding by 50% galactose for 4 weeks, followed by PMSG (50 IU/100 g) and HCG (50 IU/100 g)

3–4 weeks,

Grp i: 4 weeks GAL diet, PMSG (48 h later)

Grp ii: 4 weeks GAL diet, PMSG, 48 h later HCG (8 h later)

Grp iii: 4 weeks GAL diet, PMSG, 48 h later HCG (13 h later)

Grp iv: 4 weeks GAL diet, PMSG, 48 h later HCG (18 h later)

Ovulated OO↓

corpora lutea ↓

volume corpora lutea↑

NR (Lim)

NR (Lim)

NR (Lim)

BW↓

GR↓

Kidney W↑

Spleen w↑

Liver↑

ovarian and uterus (NC)

galactose-1-phosphate↑

  1. PND Postnatal day, Grp Group, S-Grp Sub group, (Adv) Advantage, (Lim) Limitation, FSH Follicle stimulating hormone, LH Luteinizing hormone, E2 Estradiol, P Progesterone, s.c. Sub cutaneous, PGC Primordial germ cells, PMF Primordial follicles, PriF Primary follicle, PreAF Preantral follicle, AF Antral follicle, CL Corpus luteum, ATF Atretic follicle, GC Granulosa cells, AGC Atretic granulosa cells, NC No change (no significant difference with controls), (−) = no observed, (+) = observed, ↑ = significant increase, ↓ = significant decrease, NSD No significant differences, NSI No significant increase, SD Sprague Dawley, wks Weeks, NR Not reported, BW Body weight, GR Growth rate, GAL Galactose, Gal-1-p Galactose 1-phosphat, Gat Galactitol, AlRd Aldose reductase, Alb Albumin, TP Total protein, EC Estrus cycle, VO Vaginal opening, SF Small follicles (smallest oocyte surrounded by no more than a single layer of follicular cells), MF Medium follicles(growing oocytes surrounded by more than one layer of follicular cells and had no antrum), LF Large follicles (more mature antral follicles), OO Oocyte, NEC Necrosis, APOP Apoptosis, LEA (Liver epimerase activity), GalTase Galactosyltransferase