Table 3.

Induction of PCOS by androgens and hormones and associated histological alterations

S. No	Chemical name	Species	Dose	Route & exposure duration		Findings	References
1	Estradiol valerate	Wistar Kyoto rat (adult virgin)	4 mg	Intramuscular injection (single dose)		Many atretic follicles and regressed corpora lutea.	[65]
2	Cortisone	B6A mice (neonatal)	20 μg	Subcutaneous injection (3–6 days)		Ovaries lacked corpora lutea and multiple follicular cysts were present.	[66]
3	Estrogen	Mice	20 μg	Subcutaneous injection (15 days)		Follicular cysts formed and caused anovulation. Corpora luteum was absent.	[67]
4	Dihydrot-estostero-ne (DHT)	Mice	250 μg	Subcutaneous injection (16–18 days of gestation)		Large number of small antral follicles in ovary, thin granulosa cell layer within follicle and thick theca cell layer.	[43]
5	Testoster-one + high fat diet	Wistar rat	1 mg/ 100 g b.wt	Subcutaneous injection (28 days)		Many preantral, atretic, and cystic follicles along with enlargement of stroma.	[68]
6	Testoster-one	Sprague Dawley rat	2.5 mg/d	Subcutaneous injection		Increase in cystic, atretic, and preantral follicles. Decrease in corpora lutea.	[69]
7	DHT	mice	10 mg	Subcutaneous implant (90 days)		Numerous multicystic follicles.	[36]
8	DHEA + High-fat diet	C57BL/6 Mice	6 mg/ 100 g b.wt + 60% high-fat diet	Subcutaneous injection (20 days) + oral diet		More cystic and antral follicles and reduced corpora lutea.	[37]
9	Mifeprist-one (Antiprog-esterone) (RU486)	Wistar rat	5 mg, 7.5 mg, & 10 mg	Subcutaneous Injection (9 days)		Enlarged ovaries with arrested follicular development.  Increased atretic follicular cysts and hypertrophy of granulosa cells.	[70]
10	Letrozole	C57BL/6N female mice	50 μg/d	Subcutaneous injection (5 weeks)		Irregular estrous cycle.  Many cysts in ovaries were observed.	[44]
11	Letrozole	Sprague Dawley rats	1 mg/ kg/d	Oral (15 days)		Increase in number of cystic and atretic follicles. Decreased corpus luteum and increased thickness of peripheral theca layer.	[71]
12	Dehydroe-piandrost-erone (DHEA)	Naval Medical Research Institute (NMRI) rat	6 mg/kg.b.wt	Intraperitoneal injection (20 days)		Increased number of cystic follicles, decreased number of antral follicles and corpus luteum, and anovulation.	[72]
13	Insulin + Human chorionic gonadotr-opin (hCG)	Sprague Dawley rat (70 days old)	Insulin 0.5 to 6 IU/d + hCG3 IU/d	Subcutaneous injection (twice daily for 23 days)		Decrease in luminal epithelial cell numbers and layers, glands and gland conglomerates, and decrease in endometrium and myometrium.	[73]
14	DHEA	C57BL/6 mice	6 mg/100 g.b.wt	Subcutaneous injection (20 days)		Reduction in healthy antral follicles, oocyte, and corpora lutea. Also, granulosa layer of follicles appears thin and degenerated.	[74]
15	DHEA	Sprague Dawley rat	6 mg/100 g.b.wt	Subcutaneous injection (4 weeks)		Increased number of multiple follicular cysts and increased weight of ovary.	[45]
16	Human chorionic gonadotr-opin + insulin	Sprague Dawley rat	3 IU/d (hCG) & 0.5–3 U/d insulin	Subcutaneous injection (22 days)		Numerous cystic follicles, degenerated granulosa cell layer, and reduced corpora lutea.	[75]
17	DHT	C57Bl/6 J female mice	10 mg DHT + diets varied in protein, carbs, and fat content	1 cm SILASTIC brand DHT implant (10 weeks)		Decrease and lack of corpora lutea.	[76]
18	Testoster-one	Zebra fish	0.25, 2, 10, & 100 ng/mL	Dissolved in swimming water (3 days)		Arrest in follicular growth, oligo-ovulation, and ovarian enlargement.	[77]
19	DHEA	Sprague Dawley	7 mg/ kg. b.wt	Subcutaneous injection (90 days)		Higher number of cystic and atretic follicles, hyperthecosis of internal cell layer, and thinning of the ganulosa layer.	[78]
20	Estradiol valerate	Wistar rats	4 mg	subcutaneous injection (single administration)		Reduction in size of ovary, increased size of cysts, degenerative secondary follicles were present, and Corpus lutea absent.	[46]
21	DHT	Sprague Dawley	83 µg/d/kg.b.wt	Subcutaneous injection (90 days)		Larger antral follicles, thickened theca interna, multiple cystic follicles lacking antrum and corpus lutea, and reduction in endometrium thickness.	[78]