. 2020 Apr 20;41(4):bnaa010. doi: 10.1210/endrev/bnaa010

Table 2.

Neonatal, Peripubertal, and Adult Manipulations Generating PCOS-like Features

Species	NHP			Rat				Mouse
Time window of treatment	Neonatal	Neonatal	Peripubertal	Peripubertal	Peripubertal	Peripubertal	Adult	Peripubertal	Peripubertal	Adult
Treatment	T	T	T	DHT	Letrozole	DHT	DHT	DHEA	Letrozole	Letrozole
Age of treatment	1 day	1-51 days	1 years +	21 days	21 days	21-28 days	2 months	3 weeks	3 weeks	8 weeks
Dose of treatment	35 mg/kg (sc)	25 mg (sc) or 3-10 mg/kg/day	T capsules (sc) generating ~ 1.4 ng/ml circulating T levels	83 μg/day (sc)	200 µg/day (sc)	10 mg implant (sc) or 27.5 μg/day	4 mm (sc)	7.5 mg pellet (sc)	3 mg pellet (sc), 50 μg/day	3 mg pellet (sc), 50 μg/day
Duration of treatment	1 day	50 days	4-5 years	3 months	3 months	3 months	Replaced every month	3 months	5 weeks	5 weeks
Traits approximating or biomarkers for criteria used for PCOS diagnosis in women (at least 2 out of 3 required)
Intermittent or absent ovulatory cycles	✖	✖	✖	✔	✔	✔	✔	✖	✔	✔
Elevated endogenous androgen levels or biomarkers of elevated androgens				♦	✖	♦	♦		✔	✔
Polyfollicular ovaries			✔	✔	✔	✔	✔		✔	✔
Traits accompanying PCOS
1. Ovary
↑ Ovary weight or size	✖		✖	✖	✔	✖	✖	✖	✔	✖
↑ Preantral /antral follicles				✔	✔	✖	✔	✖	✔
Antral follicle arrest				✔	✔	✔	✔	✖	✔
↑ Follicle atresia				✔	✔	✔		✖	✔
↓ Granulosa cell layer thickness				✔	✔	✔
↑ Theca cell layer thickness				✖	✔	✔
Altered follicular steroid hormone receptor expression					✔	✔
Altered AMH or AMHR2 expression			✖		✔		✔
↓ Oocyte maturation or developmental competence			✔			✔	✔
↓ Fertility or fecundity		✖	✔				✔		✔
2. Neuroendocrine regulation
↑ LH or ↑ LH:FSH ratio			✔		✔	✖	✖		✔	✔
↑ GnRH/LH pulse frequency			✔						✔
↑ Pituitary LH responsiveness to GnRH			✖				✖
↓ E₂ negative feedback					✔
↓ P₄ serum levels				✔	✔	✔
3. Metabolic traits
↑ Body weight		✖	✖	✔	✔	✔	✖	✖	✔	✖
↑ Body fat or BMI			✖	✔	✔	✔	✖	✖	✔	✖
Adipocyte hypertrophy			✖	✔	✔	✔		✖	✔
Adipogenic constraint			✖
Dyslipidemia			✖	✖	✖	✔			✔
Insulin resistance			✖	✔	✔	✔	✔	✖	✔	✖
Glucose intolerance			✖		✔	✔	✔	✖	✔	✖
Presence of steatosis						✔		✖	✖
Pancreatic β-cell defects			✖			✔	✔		✔
Hypertension						✔		✔
Left ventricular fraction shortening						✔
4. Behavioral traits
Behavioral deficits /abnormalities		✔	✔
5. References	(108)	(109)	(110-113)	(114-118)	(119-121)	(96, 102, 122-125)	(126-130)	(96, 131)	(132-135)	(136)

Abbreviations: DHEA, dehydroepiandrosterone; DHT, dihydrotestosterone; NHP, nonhuman primates; T, testosterone.

✔, PCOS-like trait present; ✖, PCOS-like trait not present; “blank,” not reported by investigators in publication, ♦, PCOS-like features could not be assessed as this trait is a feature of the hormonal modification.