Prolonged hypothyroidism severely reduces ovarian follicular reserve in adult rats

Abstract

BackgroundThere is substantial evidence both in humans and in animals that a prolonged reduction in plasma thyroid hormone concentration leads to reproductive problems, including disturbed folliculogenesis, impaired ovulation and fertilization rates, miscarriage and pregnancy complications. The objective of the present study is to examine the consequences of chronic hypothyroidism, induced in adulthood, for the size of the ovarian follicle pool. In order to investigate this, adult female rats were provided either a control or an iodide deficient diet in combination with perchlorate supplementation to inhibit iodide uptake by the thyroid. Sixteen weeks later animals were sacrificed. Blood was collected for hormone analyses and ovaries were evaluated histologically.ResultsAt the time of sacrifice, plasma thyroid-stimulating hormone concentrations were 20- to 40-fold increased, thyroxine concentrations were negligible while tri-iothyronin concentrations were decreased by 40% in the hypothyroid group, confirming that the animals were hypothyroid. Primordial, primary and preantral follicle numbers were significantly lower in the hypothyroid ovaries compared to the euthyroid controls, while a downward trend in antral follicle and corpora lutea numbers was observed. Surprisingly the percentage of atretic follicles was not significantly different between the two groups, suggesting that the reduced preantral and antral follicle numbers were presumably not the consequence of increased degeneration of these follicle types in the hypothyroid group. Plasma anti-Müllerian hormone (AMH) levels showed a significant correlation with the growing follicle population represented by the total ovarian number of primary, preantral and antral follicles, suggesting that also under hypothyroid conditions AMH can serve as a surrogate marker to assess the growing ovarian follicle population.ConclusionsThe induction of a chronic hypothyroid condition in adult female rats negatively affects the ovarian follicular reserve and the size of the growing follicle population, which may impact fertility.

Thyroid and Fertility: Recent Advances

“…A recent animal model of chronic hypothyroidism studied its effects on the growing follicle population. After rats were made hypothyroid through a 16-week low iodine diet, there was a significant decrease in the number of growing follicles (28). An in vitro study using rat ovarian cells showed that high doses of triiodothyronine (T3) induced an increase in follicle volume of 40% after 7 days in culture, while T3 decreased rates of apoptosis of granulosa cells, when they were cultured in medium deprived of serum, similar to the effects seen with FSH (29).…”

The efficacy of acupuncture for the treatment and the fertility improvement in child-bearing period female with Hashimoto Disease

“…Prolonged mild hypothyroidism may have a negative impact on the ovarian follicular reserve. [ 62 ] There is no specific treatment modality to suppress autoimmune destruction by modern medicine, therefore, seeking complementary and alternative therapy such as acupuncture in the early stage is of great significance for the treatment and fertility preservation in the child-bearing period female with HT.…”

Thyroid Hormones and Functional Ovarian Reserve: Systemic vs. Peripheral Dysfunctions

“…Recently, the association of hypothyroidism with impairment of FOR has been examined in mice and rats after administration of PTU and low-iodine diet, respectively [ 75 , 76 ]. In both cases, the number of primordial, primary and preantral follicles was reduced whereas none significant change of atretic follicles was reported.…”

“…In both cases, the number of primordial, primary and preantral follicles was reduced whereas none significant change of atretic follicles was reported. Although none explanation was supplied, the data suggested that the numeric reduction of preantral and antral follicles was not due to their degeneration under hypothyroid condition [ 76 , 77 ]. Noteworthy, in a previous paper, the same authors reported an impairment of FSH and LH surge with a concomitant alteration of the antioxidant enzymes (e.g., catalase, SOD1, and NOS) in ovaries from hypothyroid rats [ 78 ].…”