Regulation of Oocyte Microvilli Development in the Baboon Fetal Ovary by Estrogen

Abstract

We recently showed that the number of primordial follicles was reduced by 50% in ovaries of near-term fetal baboons deprived of estrogen in utero and restored to normal in animals supplemented with estrogen. Oocytes are avascular and rely on surrounding granulosa cells for nutrients, a process facilitated by microvilli on the oocyte surface. However, our understanding of oocyte microvillus development in the primate fetal ovary is incomplete. Thus, we determined whether estrogen regulates formation of oocyte microvilli in utero. Fetal ovaries were obtained on d 165 gestation (term = d 184) from baboons untreated (n = 3) or treated on d 100-165 with aromatase inhibitor CGS 20267 (estrogen suppressed by 95%; n = 5) or CGS 20267 and estradiol (n = 4). Follicles with intact (homogeneous cytoplasm) or nonintact (cytoplasm vacuolated) oocytes were quantified and the number/height of oocyte microvilli determined by electron microscopy. In untreated baboons, the mean (+/-se) number of follicles/0.08 mm(2) with an intact oocyte (11.5 +/- 0.5) was decreased (P < 0.05) by 70% in fetal ovaries of estrogen-suppressed baboons (3.4 +/- 0.2) and restored (P < 0.05) by CGS 20267 and estradiol (11.2 +/- 1.2). In estrogen-deprived fetuses, the number of microvilli/intact oocyte (23 +/- 3) was 56% lower (P < 0.01) than normal (52 +/- 5) and restored by CGS 20267 and estrogen (62 +/- 4). Moreover, in intact oocytes of estrogen-suppressed baboons, height (nm) of microvilli (105 +/- 11) was 54-62% lower (P < 0.01) than in intact oocytes of fetal ovaries of untreated (228 +/- 13) or estrogen-treated (274 +/- 17) baboons. In estrogen-replete baboons, the number of microvilli in intact oocytes was 2-fold greater (P < 0.01) than in nonintact oocytes. However, in estrogen-deprived baboons, no microvilli were detected in nonintact oocytes and the number of microvilli in intact oocytes was similar to that in nonintact oocytes of untreated fetuses. We conclude that development of microvilli in oocytes of primordial follicles in the primate fetal ovary is regulated by estrogen. Collectively, these results and those of our previous studies indicate that estrogen regulates fetal ovarian folliculogenesis and development of follicles with oocytes composed of microvilli critical for nutrient uptake and presumably long-term survival.

Immunohistochemical localization of estrogen receptors ERα and ERβ in the spiny mouse (Acomys cahirinus) ovary during postnatal development

“…These results correspond with the recent data indicating the ERs expression in the mouse (Wu et al 1992), baboon (Zachos et al 2004) and human oocytes (Wu et al 1993). This suggests that a paracrine effect of estrogens is exerted on oocyte maturation.…”

“…This suggests that a paracrine effect of estrogens is exerted on oocyte maturation. Indeed, Zachos et al (2004) reported that estrogens regulate the formation and maintenance of oocyte microvilli, which are essential for oocyte health and survival. Moreover, the use of aromatase inhibitors significantly reduced the number of microvilli and caused other morphological changes including cytoplasmic vacuolization.…”

Polycystic ovary syndrome and its developmental origins

“…More recently, persistent follicular cysts have been noted in sheep exposed prenatally to T, but not to DHT [33,166], while IUGR and LH surge defects occur in similarly treated sheep exposed to bisphenol, an estrogenic endocrinedisrupting compound [167]. At the ovarian level, reduced primordial follicle numbers occur in ovaries of late gestational fetal baboons following maternal exposure to an aromatase inhibitor [168], while decreased oocyte-granulosa cell microvilli, and presumably perturbed oocyte-granulosa cell signaling, characterize the maturing fetal ovary following diminished estrogen exposure [169,170].…”

Regulation of Baboon Fetal Ovarian Development by Placental Estrogen: Onset of Puberty Is Delayed in Offspring Deprived of Estrogen In Utero1

“…Using our nonhuman primate baboon model for studies of human reproduction [2,3], we showed that placental estrogen, the levels of which increase with advancing gestation in humans and nonhuman primates [4], regulates fetal ovarian follicle development [5,6]. Thus, in baboons in which estrogen was suppressed by treatment with the aromatase inhibitor letrozole during the second half of gestation, the number of primordial follicles formed in the fetal ovary was reduced by more than 50% [6], and the majority of follicles that developed contained unhealthy oocytes [7]. Additional studies showed that this critical action of estrogen most likely is elicited directly on the fetal ovary, which expresses estrogen receptor (ER) a/b [8,9], and not indirectly via fetal pituitary gonadotrophin support, fetal ovarian follicle-stimulating hormone (FSH) receptor expression [10], or fetal pituitary prolactin secretion [11].…”